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Aug.13.2021

Losartan; Hydrochlorothiazide, HCTZ

Indications/Dosage

Labeled

  • hypertension
  • stroke prophylaxis

Off-Label

    † Off-label indication

    For the treatment of hypertension

    NOTE: Hyzaar is available as losartan 50 mg/hydrochlorothiazide 12.5 mg, losartan 100 mg/hydrochlorothiazide 12.5 mg, losartan 100 mg/hydrochlorothiazide 25 mg dosage strengths, respectively. Individualize dosage by titration of the separate components. If the optimal dose corresponds to the ratio contained in the combination formulation, Hyzaar can be substituted.

    for patients who do not respond to monotherapy

    Oral dosage

    Adults

    Patients whose blood pressure is not adequately controlled with losartan or hydrochlorothiazide (HCTZ) monotherapy may be switched to losartan 50 mg/hydrochlorothiazide 12.5 mg PO once daily. Hyzaar is not intended as first-line therapy, except when the hypertension is severe enough that the value of achieving prompt blood pressure control exceeds the risk of initiating combination therapy. The dosage for Hyzaar is best determined by individual titration with the separate components. Adjust dosage based on clinical response after 3 weeks or more. Dosage may be increased to 2 tablets of losartan 50 mg/hydrochlorothiazide 12.5 mg once daily or 1 tablet of losartan 100 mg/hydrochlorothiazide 25 PO once daily. The maximum dosage is 100 mg/day of losartan combined with 25 mg/day of hydrochlorothiazide. The usual starting dose of losartan monotherapy is 50 mg PO once daily, with 25 mg PO recommended for patients with intravascular volume depletion (e.g., patients treated with diuretics) or a history of hepatic impairment. The addition of a diuretic has a greater effect on lowering blood pressure than increasing the losartan dosage beyond 50 mg/day. The addition of hydrochlorothiazide 12.5 mg to losartan 50 mg once daily results in an additional 50% reduction in DBP and SBP.

    Geriatric

    See adult dosage. Greater sensitivity in some older individuals is possible. Adjust dosage based on clinical response.

    for severe hypertension

    Oral dosage

    Adults

    Hyzaar is not intended as first-line therapy, except when the hypertension is severe enough that the value of achieving prompt blood pressure control exceeds the risk of initiating combination therapy. Initiate therapy with losartan 50 mg/hydrochlorothiazide 12.5 mg PO once daily. Adjust dosage based on clinical response after 2 to 4 weeks. Dosage may be increased to 1 tablet of losartan 100 mg/hydrochlorothiazide 25 PO once daily. The maximum dosage is 100 mg/day of losartan combined with 25 mg/day of hydrochlorothiazide.

    Geriatric

    See adult dosage. Greater sensitivity in some older individuals is possible. Adjust dosage based on clinical response.

    For stroke prophylaxis in hypertensive patients with left ventricular hypertrophy (LVH)

    NOTE: There is evidence that this benefit does not apply to Black patients.

    NOTE: Hyzaar is available as losartan 50 mg/hydrochlorothiazide 12.5 mg, losartan 100 mg/hydrochlorothiazide 12.5 mg, losartan 100 mg/hydrochlorothiazide 25 mg dosage strengths, respectively. Individualize dosage by titration of the separate components. If the optimal dose corresponds to the ratio contained in the combination formulation, Hyzaar can be substituted.

    Oral dosage

    Adults

    Initially, 50 mg PO losartan once daily. Maximal antihypertensive effects generally occur within 3 to 6 weeks. If needed for blood pressure (BP) reduction, add hydrochlorothiazide (HCTZ) 12.5 mg PO once daily. If additional blood pressure reduction is needed, increase the losartan dose to 100 mg, or losartan 100mg/hydrochlorothiazide 12.5 mg PO once daily may be substituted. The maximum daily dosage is losartan 100 mg and hydrochlorothiazide 25 mg. This FDA-approved indication is based on the findings of the LIFE trial which compared losartan versus atenolol in patients with hypertension and LVH.[26953] In this trial, losartan reduced the risk of stroke (nonfatal and fatal) by 25% compared to atenolol. The overall findings demonstrate that losartan is more effective than atenolol in reducing total mortality and cardiovascular morbidity and mortality, and is associated with less drug-related adverse events.[26953] In a pre-specified subanalysis of the LIFE study in diabetic hypertensives with LVH, similar findings are reported.[26954]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      100 mg/day PO losartan and 25 mg/day PO hydrochlorothiazide.

    • Geriatric

      100 mg/day PO losartan and 25 mg/day PO hydrochlorothiazide.

    • Adolescents

      Safety and efficacy have not been established.

    • Children

      Safety and efficacy have not been established.

    Patients with Hepatic Impairment Dosing

    The fixed combination product, Hyzaar, is not recommended for initial titration in patients with hepatic impairment since the appropriate 25 mg starting dose of losartan cannot be administered. See Losartan monograph for dosing in patients with hepatic impairment. Hydrochlorothiazide should be used with caution in patients with hepatic disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

    Patients with Renal Impairment Dosing

    CrCl more than 30 mL/min: No dosage adjustment is necessary.

    CrCl is 30 mL/min or less: Combination therapy with losartan and hydrochlorothiazide is not recommended. Thiazide diuretics are not effective in this setting.

     

    Intermittent hemodialysis

    Combination therapy with hydrochlorothiazide is not recommended in patients with CrCl is 30 mL/min or less. Thiazide diuretics are generally not effective in this setting.

    † Off-label indication
    Revision Date: 08/13/2021, 12:37:29 PM

    References

    26953 - Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:995-1003.26954 - Lindholm LH, Ibsen H, Dahlof B, et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:1004-1010.

    How Supplied

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Hyzaar 50mg-12.5mg Tablet (00006-0717) (Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Hyzaar 50mg-12.5mg Tablet (78206-0139) (Organon LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (52343-0116) (Acetris Health, LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (62332-0048) (Alembic Pharmaceuticals, Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (60505-2915) (Apotex Corp) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (65862-0468) (Aurobindo Pharma USA Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (42291-0393) (AvKARE, Inc.) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (50268-0513) (AvPAK; a Division of AvKARE Inc) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (57237-0207) (Citron Pharma LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (59762-0011) (Greenstone Ltd) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (00054-0126) (Hikma Pharmaceuticals USA Inc.) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (59746-0337) (Jubilant Cadista Pharmaceuticals Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (68180-0215) (Lupin Pharmaceuticals, Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (33342-0050) (MacLeods Pharma) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (63739-0527) (McKesson Packaging Inc) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (51079-0757) (Mylan Institutional LLC ) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (00378-1418) (Mylan Pharmaceuticals Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (16714-0226) (NorthStar Rx LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (00603-4228) (Par Pharmaceuticals, an Endo Company) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (43063-0873) (PD-Rx Pharmaceuticals, Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (43063-0986) (PD-Rx Pharmaceuticals, Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (72789-0162) (PD-Rx Pharmaceuticals, Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (00781-5816) (Sandoz Inc. a Novartis Company) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (00781-5206) (Sandoz Inc. a Novartis Company) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (43547-0423) (Solco Healthcare US LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (00093-7367) (Teva Pharmaceuticals USA) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (13668-0116) (Torrent Pharma, Inc) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (29300-0190) (Unichem Pharmaceuticals USA, Inc) nullLosartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet package photo

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 50mg-12.5mg Tablet (68382-0142) (Zydus Pharmaceuticals (USA) Inc.) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Hyzaar 100mg-12.5mg Tablet (00006-0745) (Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Hyzaar 100mg-12.5mg Tablet (78206-0140) (Organon LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Hyzaar 100mg-25mg Tablet (00006-0747) (Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Hyzaar 100mg-25mg Tablet (78206-0141) (Organon LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Hyzaar 100mg-25mg Tablet (55289-0522) (PD-Rx Pharmaceuticals, Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Hyzaar 100mg-25mg Tablet (58864-0659) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (52343-0117) (Acetris Health, LLC) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (62332-0049) (Alembic Pharmaceuticals, Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (68084-0959) (American Health Packaging) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (60505-2916) (Apotex Corp) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (65862-0469) (Aurobindo Pharma USA Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (42291-0394) (AvKARE, Inc.) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (50268-0514) (AvPAK; a Division of AvKARE Inc) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (57237-0208) (Citron Pharma LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (59762-0012) (Greenstone Ltd) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (00054-0277) (Hikma Pharmaceuticals USA Inc.) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (59746-0338) (Jubilant Cadista Pharmaceuticals Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (68180-0216) (Lupin Pharmaceuticals, Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (33342-0051) (MacLeods Pharma) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (63739-0528) (McKesson Packaging Inc) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (00378-1419) (Mylan Pharmaceuticals Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (16714-0224) (NorthStar Rx LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (00603-4229) (Par Pharmaceuticals, an Endo Company) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (00781-5817) (Sandoz Inc. a Novartis Company) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (00781-5204) (Sandoz Inc. a Novartis Company) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (43547-0425) (Solco Healthcare US LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (00093-7369) (Teva Pharmaceuticals USA) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (13668-0117) (Torrent Pharma, Inc) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet (29300-0191) (Unichem Pharmaceuticals USA, Inc) nullLosartan Potassium/Hydrochlorothiazide 100mg-12.5mg Tablet package photo

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (52343-0118) (Acetris Health, LLC) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (62332-0050) (Alembic Pharmaceuticals, Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (68084-0749) (American Health Packaging) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (60505-2917) (Apotex Corp) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (65862-0470) (Aurobindo Pharma USA Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (42291-0395) (AvKARE, Inc.) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (50268-0515) (AvPAK; a Division of AvKARE Inc) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (57237-0209) (Citron Pharma LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (59762-0015) (Greenstone Ltd) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (00054-0127) (Hikma Pharmaceuticals USA Inc.) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (59746-0339) (Jubilant Cadista Pharmaceuticals Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (68180-0217) (Lupin Pharmaceuticals, Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (33342-0052) (MacLeods Pharma) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (63739-0529) (McKesson Packaging Inc) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (00378-1420) (Mylan Pharmaceuticals Inc.) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (16714-0225) (NorthStar Rx LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (00603-4230) (Par Pharmaceuticals, an Endo Company) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (00781-5818) (Sandoz Inc. a Novartis Company) (off market)

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (00781-5207) (Sandoz Inc. a Novartis Company) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (43547-0424) (Solco Healthcare US LLC) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (00093-7368) (Teva Pharmaceuticals USA) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (13668-0118) (Torrent Pharma, Inc) null

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (29300-0192) (Unichem Pharmaceuticals USA, Inc) nullLosartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet package photo

    Losartan Potassium, Hydrochlorothiazide Oral tablet

    Losartan Potassium/Hydrochlorothiazide 100mg-25mg Tablet (68382-0143) (Zydus Pharmaceuticals (USA) Inc.) (off market)

    Description/Classification

    Description

    Losartan and hydrochlorothiazide (HCTZ) are used together in a once daily oral preparation to manage hypertension. Hydrochlorothiazide is a thiazide diuretic. Losartan and its metabolite (E-3174) are specific and selective angiotensin II antagonists. Because AT1 receptors are nearly saturated at the starting dose for most angiotensin II antagonists, the antihypertensive dose-response curve of these drugs are nonlinear, with proportionally small decreases in blood pressure attained with increased dosage. Greater antihypertensive efficacy is achieved by adding a small dose of a diuretic to the angiotensin II antagonist. Losartan is associated with dose-related antiproteinuric and uricosuric effects. Losartan tends to reverse the potassium loss and blunts the rise in serum uric acid levels associated with hydrochlorothiazide. Because losartan does not inhibit angiotensin converting enzyme (ACE), it does not result in bradykinin accumulation which is theorized to cause the cough and angioedema associated with ACE inhibitors. However, angioedema has been rarely associated with losartan or other angiotensin II antagonists. Hyzaar (50 mg losartan and 12.5 mg hydrochlorothiazide) was originally approved on April 28, 1995; the subsequent dosage strength (100 mg losartan and 25 mg hydrochlorothiazide) was approved on October 13, 1998.

    Classifications

    • Cardiovascular System
      • Antihypertensives
        • Agents Acting On The Renin-Angiotensin System (RAS)
          • Angiotensin-II Receptor Blockers/ARBs Plain and in Combination
            • Angiotensin-II Receptor Blocker/ARBs and Diuretic Combinations
    Revision Date: 08/13/2021, 11:41:21 AM

    References

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

    Route-Specific Administration

    Oral Administration

    • Losartan; hydrochlorothiazide may be administered without regard to meals.[32333]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
      Revision Date: 05/17/2021, 12:52:30 PM

      References

      32333 - Hyzaar (losartan potassium and hydrochlorothiazide tablets) package insert. White House Station, NJ: Merck & Co., Inc.; 2020 Aug.

      Adverse Reactions

      Mild

      • abdominal pain
      • alopecia
      • anorexia
      • anxiety
      • arthralgia
      • asthenia
      • back pain
      • cough
      • dental pain
      • diaphoresis
      • diarrhea
      • dizziness
      • drowsiness
      • dysgeusia
      • dyspepsia
      • ecchymosis
      • epistaxis
      • fatigue
      • fever
      • flatulence
      • flushing
      • headache
      • hypoesthesia
      • increased urinary frequency
      • infection
      • insomnia
      • libido decrease
      • malaise
      • muscle cramps
      • musculoskeletal pain
      • myalgia
      • nasal congestion
      • nausea
      • nocturia
      • ocular irritation
      • paresthesias
      • pharyngitis
      • photosensitivity
      • pruritus
      • purpura
      • rash
      • restlessness
      • rhinitis
      • sinusitis
      • syncope
      • tinnitus
      • tremor
      • urticaria
      • vertigo
      • vomiting
      • weakness
      • xerosis
      • xerostomia

      Moderate

      • anemia
      • angina
      • ataxia
      • blurred vision
      • chest pain (unspecified)
      • confusion
      • conjunctivitis
      • constipation
      • depression
      • dyspnea
      • edema
      • elevated hepatic enzymes
      • erythema
      • gastritis
      • glycosuria
      • gout
      • hemolysis
      • hepatitis
      • hyperbilirubinemia
      • hypercalcemia
      • hypercholesterolemia
      • hyperglycemia
      • hypertriglyceridemia
      • hyperuricemia
      • hypokalemia
      • hypomagnesemia
      • hyponatremia
      • hypotension
      • hypovolemia
      • impotence (erectile dysfunction)
      • jaundice
      • leukopenia
      • memory impairment
      • metabolic alkalosis
      • migraine
      • myasthenia
      • myopia
      • nephrolithiasis
      • orthostatic hypotension
      • palpitations
      • peripheral neuropathy
      • pneumonitis
      • sialadenitis
      • sinus tachycardia
      • thrombocytopenia
      • xanthopsia

      Severe

      • agranulocytosis
      • anaphylactoid reactions
      • angioedema
      • aplastic anemia
      • arrhythmia exacerbation
      • atrial fibrillation
      • AV block
      • azotemia
      • bradycardia
      • erythema multiforme
      • exfoliative dermatitis
      • hemolytic anemia
      • hyperkalemia
      • interstitial nephritis
      • myocardial infarction
      • ocular hypertension
      • oliguria
      • pancreatitis
      • pulmonary edema
      • renal failure (unspecified)
      • rhabdomyolysis
      • skin cancer
      • Stevens-Johnson syndrome
      • stroke
      • teratogenesis
      • toxic epidermal necrolysis
      • vasculitis
      • ventricular fibrillation
      • ventricular tachycardia
      • visual impairment

      Cough was reported in 2.6% of losartan; hydrochlorothiazide-treated patients compared to 2.3% of placebo-treated patients in controlled clinical trials. The incidence of cough appears to be lower with losartan than with an angiotensin converting enzyme inhibitor (ACEI); losartan does not inhibit angiotensin converting enzyme (kinase II), which is thought to be responsible for the ACEI-induced cough. In comparative studies, the incidence of cough in losartan-treated patients with a prior history of ACEI-induced cough was similar to that associated with hydrochlorothiazide or placebo therapy. Cases of cough, including positive re-challenges, have been reported with the use of losartan in postmarketing experience.[32333]

      Dizziness was reported in 5.7% of losartan; hydrochlorothiazide-treated patients in clinical trials compared to 2.9% of placebo-treated patients. Asthenia/fatigue and headache were also reported in 1% or more of losartan; hydrochlorothiazide-treated patients, but were as or more common in the placebo group. Nervous system/psychiatric events reported in patients treated with losartan monotherapy without regard to causality include: anxiety, ataxia, confusion, depression, dream abnormality, hypoesthesia, insomnia, libido decrease, memory impairment, migraine, nervousness, panic disorder, paresthesias, peripheral neuropathy, sleep disorder, drowsiness, tremor, and vertigo. Restlessness and weakness have been reported during hydrochlorothiazide monotherapy.[32333]

      Impotence (erectile dysfunction) has been reported in patients taking losartan monotherapy and is possible in patients taking losartan; hydrochlorothiazide.[32333]

      Adverse reactions reported in losartan; hydrochlorothiazide-treated patients in clinical trials and more frequently than placebo include: edema/swelling (1.3% vs. 1.2%) and palpitations (1.4% vs. 0%). Patients treated with diuretics may become intravascularly volume-depleted (hypovolemia), and symptomatic hypotension may occur after initiation of therapy with losartan; hydrochlorothiazide. Chest pain (unspecified), orthostatic effects (e.g., orthostatic hypotension), syncope, angina pectoris, arrhythmia exacerbation (including atrial fibrillation, sinus bradycardia, sinus tachycardia, ventricular tachycardia and ventricular fibrillation), CVA (stroke), myocardial infarction, and second degree AV block have been reported with losartan.[32333]

      Anaphylactic reactions (anaphylactoid reactions) and angioedema have been reported rarely with losartan and may occur during therapy with losartan; hydrochlorothiazide. Theoretically, angiotensin II receptor antagonists (ARBs) should be less likely than angiotensin converting enzyme inhibitors (ACEIs) to precipitate angioedema because ARBs do not cause accumulation of kinins. However, angioedema (swelling of lips and eyelids, facial rash) has been reported in patients receiving ARBs, including in patients with a prior history of angioedema during ACE inhibitor therapy (see Contraindications). Some of these patients previously experienced angioedema with other drugs including ACEIs. One patient receiving losartan also had a history of aspirin and penicillin allergies. Facial edema has also been reported with losartan.[32333]

      Hypersensitivity reactions may occur during therapy with losartan; hydrochlorothiazide. Vasculitis, including Henoch-Schoenlein purpura, has been reported with losartan. Necrotizing angiitis (vasculitis and cutaneous vasculitis) has been reported with hydrochlorothiazide.[32333]

      Clinically significant laboratory abnormalities are rarely reported with losartan. Small decreases in hemoglobin (0.14 grams percent) and hematocrit (0.72 volume percent) occurred frequently during losartan; hydrochlorothiazide therapy; no patient discontinued due to anemia. However, anemia has been reported with losartan monotherapy. Elevated hepatic enzymes and elevated bilirubin concentrations (hyperbilirubinemia) have been reported occasionally during antihypertensive therapy with losartan; hydrochlorothiazide; without requiring discontinuation from therapy. Hepatitis is rarely reported with losartan. Thiazide diuretics have been associated with intrahepatic cholestatic jaundice.[32333]

      Rash (unspecified) was reported in 1.4% of losartan; hydrochlorothiazide-treated patients compared to 0% of placebo-treated patients in clinical trials. Superficial peeling of the palms with hemolysis has been reported in one patient receiving losartan monotherapy. Erythroderma (exfoliative dermatitis) has been reported during losartan postmarketing experience. Alopecia, dermatitis, dry skin (xerosis), ecchymosis, erythema, flushing, photosensitivity, pruritus, diaphoresis, and urticaria have also been reported in patients treated with losartan. Adverse dermatologic reactions to hydrochlorothiazide and other thiazide diuretics are uncommon but may occur. These reactions include photosensitivity, urticaria, erythema multiforme including Stevens-Johnson syndrome, and exfoliative dermatitis including toxic epidermal necrolysis (TEN).[32333].

      Hydrochlorothiazide has been associated with hyperglycemia and glycosuria without regard to causality. Diabetic patients receiving losartan; hydrochlorothiazide may require dosage adjustment of insulin or oral hypoglycemic agents.[32333]

      While serious hematological reactions are rare; aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, and thrombocytopenia have been reported with hydrochlorothiazide therapy. Thrombocytopenia has also been reported during postmarketing experience with losartan; hydrochlorothiazide.[32333]

      Hyperuricemia may occur in patients receiving thiazide diuretics. In predisposed individuals, frank gout or nephrolithiasis may be precipitated. Diuretic-induced acute gouty arthritis and nephrolithiasis are extremely rare in patients with no prior history of gout. Losartan in combination with hydrochlorothiazide attenuates the diuretic-induced hyperuricemia. Although gout has been reported in losartan-treated patients, in a single dose study of losartan, there was a small uricosuric effect leading to a mean decrease in serum uric acid of less than 0.4 mg/dL during chronic oral administration. If some manifestation of gout occurs in a patient who requires diuretic therapy for effective treatment of hypertension, allopurinol or a uricosuric agent can be given to prevent recurrent gouty attacks without diminishing the antihypertensive effect of losartan; hydrochlorothiazide.[32333]

      Thiazide diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia. Thiazides may also decrease urinary calcium excretion and may cause intermittent and slight elevations of serum calcium in the absence of known disorders of calcium metabolism. The development of marked hypercalcemia may be evidence of hidden hyperparathyroidism. If hypercalcemia occurs, losartan; hydrochlorothiazide should be discontinued before carrying out tests for parathyroid function.[32333]

      Although hypercholesterolemia and/or hypertriglyceridemia have been associated with thiazide diuretic therapy, data from long-term studies suggest that diuretic-induced lipid abnormalities are not clinically significant.[24090] After approximately one year of treatment, total serum cholesterol concentrations will subside to baseline or lower, suggesting that diuretic therapy does not increase coronary heart disease risk. Nevertheless, it would be prudent to monitor serum cholesterol and triglyceride concentrations periodically in hypertensive patients receiving losartan; hydrochlorothiazide.[32333]

      Abdominal pain was reported in 1.2% of losartan; hydrochlorothiazide-treated patients vs. 0.6% of placebo-treated patients in clinical trials. Diarrhea and nausea were also reported in 1% or more of losartan; hydrochlorothiazide-treated patients, but were as, or more common in the placebo group. Anorexia, constipation, dental pain, xerostomia, dyspepsia, flatulence, gastritis, and vomiting have been reported with losartan. Sialadenitis, cramping, and gastric irritation have been reported with hydrochlorothiazide.[32333]

      Back pain was reported in 2.1% of losartan; hydrochlorothiazide-treated patients in clinical trials compared to 0.6% of placebo-treated patients. Muscle spasm has been reported with hydrochlorothiazide. Arm pain, arthralgia, arthritis, fibromyalgia, hip pain, joint swelling, knee pain, leg pain, muscle cramps, myasthenia (muscle weakness), musculoskeletal pain, myalgia, shoulder pain, and stiffness have been reported with losartan. Rare cases of rhabdomyolysis have been reported during postmarketing experience with angiotensin II receptor antagonists.[32333]

      Dysgeusia has been reported in patients taking losartan; hydrochlorothiazide therapy.[32333]

      Respiratory-related adverse events that occurred more frequently in losartan; hydrochlorothiazide-treated patients in clinical trials than in placebo-treated patients include: sinusitis (1.2% vs. 0.6%) and upper respiratory infection (6.1% vs. 4.6%). Bronchitis and pharyngitis were reported in 1% or more of losartan; hydrochlorothiazide-treated patients but were as, or more, common in the placebo group. Fever, malaise, dyspnea, epistaxis, nasal congestion, pharyngeal discomfort, respiratory congestion, rhinitis, and sinus disorder have been reported with losartan. Fever and respiratory distress including pneumonitis and pulmonary edema have been reported with hydrochlorothiazide.[32333]

      Pancreatitis has been reported rarely in patients receiving thiazide diuretics. Clinical manifestations frequently include pain in the abdomen, abdominal distention, nausea, vomiting, and low-grade fever. Pancreatitis can occur within 2 weeks of initiation of therapy or after several months of therapy. If signs and/or symptoms suggestive of pancreatitis develop in a patient receiving losartan; hydrochlorothiazide, drug therapy should be discontinued.[32333]

      Due to the potential for teratogenesis, losartan; hydrochlorothiazide should not be used during pregnancy. Drugs that affect the renin-angiotensin system have been associated with fetal and neonatal abnormalities when administered to women during the second or third trimesters of pregnancy. Adverse fetal and neonatal effects have included hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, oligohydramnios, and death. Oligohydramnios has been associated with craniofacial deformation and hypoplastic lung development. If oliguria or hypotension occurs in a neonate with a history of in utero exposure to losartan; hydrochlorothiazide, blood pressure and renal perfusion support may be required, as well as exchange transfusion or dialysis to reverse hypotension and/or support decreased renal function.[32333]

      Losartan; hydrochlorothiazide may result in ophthalmic and otic adverse reactions. Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. Discontinue hydrochlorothiazide as rapidly as possible and consider prompt medical or surgical treatment if the ocular hypertension remains uncontrolled.[42865] Transient blurred vision and xanthopsia have also been reported during hydrochlorothiazide monotherapy. Blurred vision, ocular irritation (i.e., burning/stinging in the eye), conjunctivitis, visual impairment (i.e., decrease in visual acuity), and tinnitus have been reported with losartan.[32333]

      Minor increases in blood urea nitrogen or serum creatinine were observed in 0.6% and 0.8%, respectively, of patients treated with losartan; hydrochlorothiazide for hypertension. Treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure (unspecified) and/or death in patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure). Similar outcomes have been reported with losartan.[32333] In the ELITE study, renal dysfunction (defined as a persistent increase in serum creatinine of 0.3 mg/dl) occurred in 10.5% of elderly heart failure patients treated with losartan and in 10.5% of patients treated with an ACE inhibitor (captopril).[24866] Nocturia, increased urinary frequency, and urinary tract infection have also been reported with losartan. Renal failure, renal dysfunction, and interstitial nephritis have been reported with hydrochlorothiazide.[32333]

      Hypokalemia (serum potassium less than 3.5 mEq/L) has been observed in 6.7% patients; whereas hyperkalemia (serum potassium greater than 5.7 mEq/L) has been observed in 0.4% of patients receiving losartan; hydrochlorothiazide. No patients required discontinuation of therapy from the combination product in controlled clinical trials due to changes in serum potassium. Hyponatremia has also been reported with losartan monotherapy. All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance: hyponatremia, hypochloremic alkalosis, and hypokalemia. Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis. Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.[32333]

      Hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer. An FDA Sentinel Initiative study found that increased risk was mostly for squamous cell carcinoma and in White patients taking large cumulative doses. The increased risk for the overall population was approximately 1 additional case per 16,000 patients per year. For White patients taking a cumulative dose more than 50,000 mg, the risk increased to approximately 1 additional case per 6,700 patients per year.[32333]

      Revision Date: 08/13/2021, 03:15:57 PM

      References

      24090 - Freis ED. Critique of the clinical importance of diurectic-induced hypokalemia and elevated cholesterol level. Arch Intern Med 1989;149:2640-8.24866 - Pitt B, Segal R, Martinez FA, et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997;349:747-52.32333 - Hyzaar (losartan potassium and hydrochlorothiazide tablets) package insert. White House Station, NJ: Merck & Co., Inc.; 2020 Aug.41281 - Food and Drug Administration MedWatch. Angiotensin Receptor Blockers (ARBs): Ongoing Safety Review for Cancer Risk. Retrieved July 15, 2010. htm.http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm219185.htm42865 - Amturnide (aliskiren; amlodipine; hydrochlorothiazide) package insert. East Hanover, NJ: Novartis; 2015 Mar.44483 - Food and Drug Administration MedWatch. Angiotensin Receptor Blockers (ARBs): Drug Safety Communication-Drug Safety Review Completed Retrieved June 2, 2011. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm219185.htm

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • anuria
      • sulfonamide hypersensitivity
      • thiazide diuretic hypersensitivity
      • ACE-inhibitor induced angioedema
      • angioedema
      • asthma
      • breast-feeding
      • children
      • diabetes mellitus
      • electrolyte imbalance
      • geriatric
      • gout
      • heart failure
      • hepatic disease
      • hypercalcemia
      • hyperglycemia
      • hyperkalemia
      • hyperuricemia
      • hypokalemia
      • hypomagnesemia
      • hyponatremia
      • hypotension
      • hypovolemia
      • infants
      • neonates
      • orthostatic hypotension
      • pancreatitis
      • penicillin hypersensitivity
      • pregnancy
      • renal artery stenosis
      • renal disease
      • renal failure
      • renal impairment
      • skin cancer
      • sunlight (UV) exposure
      • surgery
      • sympathectomy
      • syncope
      • systemic lupus erythematosus (SLE)

      Thiazide diuretics such as hydrochlorothiazide have been associated with a slight increase in serum cholesterol and triglyceride concentrations. Data from long-term studies, however, suggest diuretic-induced cholesterol changes are not clinically significant and do not contribute to coronary heart disease risk.[24090]

      Thiazide diuretics are contraindicated in patients with known thiazide diuretic hypersensitivity. According to the manufacturer, hydrochlorothiazide is specifically contraindicated in patients with sulfonamide hypersensitivity. Hypersensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma; however, reactions are more likely to occur in patients with such history. Although thiazide diuretics are sulfonamide derivatives, sulfonamide cross-sensitivity has rarely been documented.[23511] [26922] [32381] Until further data are available, thiazide diuretics should be used with caution in patients with sulfonamide hypersensitivity. Thiazide diuretics do not contain the N4-aromatic amine or the N1-substituent which are present in sulfonamide antibiotics.[32380] Non-arylamine sulfonamide derivatives, such as thiazide diuretics, have been proposed to have a lower risk of allergic reactions in patients with sulfonamide allergy, presumably due to lack of an arylamine group at the N4 position (a proposed structural site of action for sulfonamide allergy).[32380] [32381] One large retrospective cohort study has reported that in patients with the presence of an allergic reaction after exposure to a sulfonamide antibiotic, 9.9% had an allergic reaction after receiving a non-antibiotic sulfonamide derivative, while in patients who lacked an allergic reaction after sulfonamide antibiotic exposure, 1.6% had an allergic reaction after administration of a non-antibiotic sulfonamide derivative (adjusted odds ratio 2.8; 95% CI, 2.1 to 3.7).[32382] A causal relationship between sulfonamide hypersensitivity and allergic reactions with non-arylamine sulfonamide derivatives has not been definitively established and remains controversial.[23511] [26922] [32380] [32381] In general, patients with a documented sulfonamide allergy are considered to be predisposed for development of allergic drug reactions.[32380] [32382] Also, patients with a history of sulfonamide hypersensitivity or penicillin hypersensitivity who receive hydrochlorothiazide may also be at increased risk for the development of an idiosyncratic reaction resulting in transient myopia and acute angle-closure glaucoma. Discontinue hydrochlorothiazide promptly if this reaction occurs.[42865]

      Losartan; hydrochlorothiazide is contraindicated in patients with anuria since thiazide diuretics are considered ineffective when the creatinine clearance is less than 30 ml/minute. Hydrochlorothiazide should be used cautiously in patients with renal disease resulting in renal failure or severe renal impairment because the drug decreases the glomerular filtration rate and may precipitate azotemia in these patients. Losartan should be used with caution in patients whose renal function is critically dependent on the activity of the renin-angiotensin-aldosterone system (RAS) (e.g., patients with heart failure). Changes in renal function have been reported in susceptible individuals receiving losartan, with these changes reversible upon discontinuation of therapy in some patients. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor antagonists affect the RAS system and have caused increases in serum creatinine in susceptible individuals. Although serum creatinine returns to baseline or stabilizes in most patients with continued use, oliguria, progressive azotemia, and rarely, acute renal failure have occurred. In addition, ACEIs have been associated with azotemia in patients with unilateral or bilateral renal artery stenosis. Although losartan has not been studied in renal artery stenosis, similar effects to the ACEIs might be anticipated due to losartan's pharmacology. Renal function should be monitored in patients receiving losartan; hydrochlorothiazide.

      Losartan; hydrochlorothiazide is not recommended for titration in patients with hepatic impairment since the appropriate 25 mg starting dose of losartan cannot be administered. Losartan requires dosage adjustment in patients with hepatic disease. Patients with mild to moderate alcoholic cirrhosis demonstrated significantly increased losartan and active metabolite plasma concentrations which were 5 and 1.7 times higher, respectively, compared to normal subjects. Hydrochlorothiazide should be used with caution in patients with hepatic disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

      Losartan; hydrochlorothiazide should be used with caution in patients who have hypovolemia. Intravascular volume depletion increases the risk of symptomatic hypotension during therapy. When initiating therapy in these patients, lower doses are recommended. Losartan; hydrochlorothiazide should be used with great care in patients who exhibit signs of hypotension. Volume depletion should be corrected prior to the administration of losartan; hydrochlorothiazide. Orthostatic hypotension may occur during treatment with thiazide diuretics.[32529] Orthostatic hypotension can be exacerbated by concurrent use of alcohol, narcotics, or antihypertensive drugs. Excessive hypotension during thiazide diuretic therapy can result in syncope. An increased risk of falls has been reported for elderly patients receiving thiazide diuretics.[32527] [32528] In addition, the antihypertensive effects of thiazides may be enhanced in other patients predisposed for orthostatic hypotension, including the post-sympathectomy patient.

      Anaphylactic reactions (anaphylactoid reactions) and angioedema have been reported with angiotensin II receptor antagonists. Theoretically, angiotensin II receptor antagonists should be less likely than angiotensin converting enzyme inhibitors (ACEIs) to precipitate angioedema because angiotensin II receptor antagonists do not cause accumulation of kinins.[32325] However, angioedema (swelling of lips and eyelids, facial rash) has rarely been reported in patients receiving angiotensin II receptor antagonists, including in patients with a prior history of ACE-inhibitor induced angioedema. While angiotensin II receptor antagonists have been suggested as potential alternatives to ACE inhibitors for patients who experience angioedema due to a lower frequency of associated angioedema [32325] [32327], the safety of angiotensin II receptor antagonists in patients with a prior history of ACE-inhibitor induced angioedema has not been definitively established.[32326] [32328] [32329] [32330] It is prudent to use substantial caution when prescribing losartan; hydrochlorothiazide in patients with a history of ACE-inhibitor induced angioedema. Some authors have recommended that angiotensin II receptor antagonists should be avoided in patients with a history of angioedema, especially those with ACE-inhibitor induced angioedema.[32331]

      In patients undergoing major surgery or during anesthesia with agents that lower blood pressure, losartan may enhance hypotensive effects via angiotensin II blockade. Therefore, losartan; hydrochlorothiazide should be used with caution prior to surgery. If hypotension occurs during surgery and/or anesthesia and is considered to be due to blockade of angiotensin II formation, it can be corrected by volume expansion.

      When pregnancy is detected, discontinue losartan; hydrochlorothiazide therapy as soon as possible. Women of child-bearing age should be made aware of the potential risk and losartan; hydrochlorothiazide should only be given after careful counseling and consideration of risks and benefits. When used during the second and third trimesters, drugs that affect the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce fetal renal function and increase fetal and neonatal morbidity and death. Use of drugs that affect the renin-angiotensin system during pregnancy can cause fetal death or injury such as hypotension, neonatal skull hypoplasia, reversible or irreversible renal failure and death. Anhydramnios and oligohydramnios have also been reported. Development of oligohydramnios may be associated with decreased fetal renal function leading to anuria and renal failure and results in fetal limb contractures, craniofacial deformation, hypotension, hypoplastic lung development, and death. [32333] Retrospective data indicate that first trimester use of ACE inhibitors has been associated with a potential risk of birth defects.[32294] However, a much larger observational study (n = 465,754) found that the risk of birth defects was similar in infants exposed to ACE inhibitors during the first trimester, in infants exposed to other antihypertensives during the first trimester, and in those whose mothers were hypertensive but were not treated.[46406] Infants born to mothers with hypertension, either treated or untreated, had a higher risk of birth defects than those born to mothers without hypertension. The authors concluded that the presence of hypertension likely contributed to the development of birth defects rather than the use of medications. An observational cohort study evaluating the outcomes of angiotensin receptor blockers (ARBs) use during the first trimester of pregnancy found an increased rate of major birth defects compared to non-hypertensive pregnancies, 5.4% and 3%, respectively; the difference did not reach statistical significance. The authors noted that there was a higher risk of major birth defects with ARB therapy beyond 6 weeks of gestation compared to discontinuation of ARBs before week 6, 7.3% and 2.8%, respectively. The rates of prematurity and reduced birth weight were also increased in the ARB group. There were no statistically significant differences in the rates of major birth defects, spontaneous abortions, or preterm births between women with chronic hypertension treated with an ARB versus methyldopa.[64367] Thiazide diuretics can cross the placenta resulting in umbilical cord concentrations similar to maternal plasma concentrations and amniotic fluid concentrations that are up to 19 times greater than in the umbilical vein. Based on the results from one large study, first trimester use of thiazide and related diuretics may increase the risk for congenital defects. In addition to malformations, other fetal risks associated with thiazide use during pregnancy include hypoperfusion, fetal or neonatal jaundice, hypoglycemia, thrombocytopenia, hyponatremia, hypokalemia, and death from maternal complications. Once pregnancy is detected, ultrasound examination should be performed if losartan; hydrochlorothiazide exposure occurs beyond the first trimester. In rare cases when another antihypertensive agent cannot be used to treat a pregnant patient, serial ultrasound examinations should be performed to assess the intraamniotic environment. If oligohydramnios is observed, discontinue losartan; hydrochlorothiazide unless it is considered life-saving for the mother. It should be noted that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe newborns with histories of in utero exposure to losartan; hydrochlorothiazide for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, blood pressure and renal perfusion support may be required, as well as exchange transfusion or dialysis to reverse hypotension and/or support decreased renal function.[32333]

      Patients with pre-existing significant hyponatremia, hyperkalemia, hypokalemia, hypomagnesemia, and/or hypercalcemia should have their electrolyte imbalances corrected before losartan; hydrochlorothiazide is initiated. Thiazide diuretics such as hydrochlorothiazide have been shown to increase the urinary excretion of magnesium and decrease urinary calcium excretion. Losartan; hydrochlorothiazide may reduce, elevate or leave potassium levels unchanged in individual patients. All patients should be monitored closely for clinical signs of fluid or electrolyte imbalance. Thiazides may worsen dilutional hyponatremia, especially in elderly individuals. Greater sensitivity to the usual dosage of hydrochlorothiazide may occur in some elderly patients. In general, drug dose selection for an elderly patient should be cautious, usually starting at the low end of the adult dosage range. Losartan and active metabolite plasma concentrations are similar in elderly and younger hypertensive adults. Plasma losartan concentrations are about twice as high in females versus males, but the plasma concentrations of the active metabolite are unchanged. However, blood pressure responses to losartan are similar, regardless of age or gender.

      According to the manufacturer, because of the potential for adverse effects on the nursing infant, a decision should be made to discontinue breast-feeding or discontinue losartan; hydrochlorothiazide therapy. It is not known whether losartan is excreted into human milk. Hydrochlorothiazide has been detected in human breast milk.[32333] The American Academy of Pediatrics (AAP) has not evaluated the use of losartan in breast-feeding mothers; however, the AAP does consider hydrochlorothiazide to be usually compatible with breast-feeding.[27500] Thiazide diuretics distribute into breast milk, and it has been recommended by some manufacturers that women do not nurse while receiving selected thiazide diuretics. High doses of some thiazide diuretics have been used off-label to suppress lactation, and thus should be used with caution during establishment of breast-feeding. Some experts consider 50 mg or less to be compatible with breast-feeding. The ACE inhibitors captopril, enalapril, benazepril, and quinapril are excreted in human breast milk in very small quantities; therefore, a clinically significant risk to a breast-feeding infant is not expected unless high doses are required.[27500] [29147] [46352] [46354] [63903] If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.[32333]

      Safety and effectiveness of losartan; hydrochlorothiazide have not been established in neonates, infants, and children less than 18 years old.

      Hyperglycemia or impaired glucose tolerance can occur during hydrochlorothiazide therapy. In patients with diabetes mellitus who are receiving losartan; hydrochlorothiazide, blood glucose levels should be monitored frequently. Adjustment of insulin and/or oral hypoglycemic agents may be required.

      Thiazide diuretics have been reported to cause pancreatitis. Losartan; hydrochlorothiazide should be used with caution in patients with a history of pancreatitis.

      Losartan; hydrochlorothiazide should be administered cautiously to patients with gout or hyperuricemia since thiazide diuretics such as hydrochlorothiazide have been reported to reduce the clearance of uric acid.

      Hydrochlorothiazide has been reported to activate or exacerbate systemic lupus erythematosus (SLE).

      Instruct patients taking hydrochlorothiazide to avoid excessive sunlight (UV) exposure and undergo regular skin cancer screening. Hydrochlorothiazide has been associated with an increased risk of non-melanoma skin cancer. An FDA Sentinel Initiative study found that increased risk was mostly for squamous cell carcinoma and in White patients taking large cumulative doses. The increased risk for the overall population was approximately 1 additional case per 16,000 patients per year. For White patients taking a cumulative dose more than 50,000 mg, the risk increased to approximately 1 additional case per 6,700 patients per year.[32333] Photosensitivity has also been reported with thiazide diuretics like hydrochlorothiazide; discontinue if phototoxicity occurs.[30713]

      No overall differences in effectiveness were observed between geriatric patients and younger adults during clinical trials of losartan; hydrochlorothiazide; the reported adverse events were somewhat more frequent in the elderly compared to non-elderly patients for both the losartan; hydrochlorothiazide and control groups. Greater sensitivity to the usual dosage of hydrochlorothiazide or losartan may occur in some geriatric patients, and care should be taken in initial dose selection, usually starting at the low end of the usual adult dose range.[32333] Thiazides may worsen dilutional hyponatremia, especially in geriatric individuals. An increased risk of falls has been reported for older adult patients receiving thiazide diuretics.[32527] [32528] Monitor renal function and for clinical signs of acid/base, fluid, or electrolyte imbalances. According to the Beers Criteria, diuretics such as hydrochlorothiazide are considered potentially inappropriate medications (PIMs) in geriatric patients and should be used with caution due to the potential for causing or exacerbating SIADH or hyponatremia. Sodium levels should be closely monitored when starting or changing dosages of diuretics in older adults.[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities; antihypertensive regimens should be individualized to achieve the desired outcome while minimizing adverse effects. Antihypertensives may cause dizziness, postural hypotension, fatigue, and there is an increased risk for falls. In addition, diuretics may cause fluid and electrolyte imbalances and may precipitate or exacerbate urinary incontinence.[60742]

      Revision Date: 08/13/2021, 01:16:22 PM

      References

      23511 - Sullivan TJ. Cross-reactions among furosemide, hydrochlorothiazide, and sulfonamides. JAMA 1991;265:120-1.24090 - Freis ED. Critique of the clinical importance of diurectic-induced hypokalemia and elevated cholesterol level. Arch Intern Med 1989;149:2640-8.26922 - Knowles S, Shapiro L, Shear NH. Should celecoxib be contraindicated in patients who are allergic to sulfonamides? Revisiting the meaning of "sulfa" allergy. Drug Saf 2001;24:239-247.27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.29147 - Lotensin (benazepril) package insert. Parsippany, NJ: Validus Pharmaceuticals LLC; 2019 Jan.30713 - Moore DE. Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management. Drug Saf 2002;25:345-72.32294 - Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 2006;354:2443-51.32325 - Dykewicz MS. Cough and angioedema from angiotensin-converting enzyme inhibitors: new insights into mechanisms and management. Curr Opin Allergy Clin Immunol 2004;4:267-70.32326 - Tan EK, Grattan CE. Drug-induced urticaria. Expert Opin Drug Saf 2004;3:471-84.32327 - Cicardi M, Zingale LC, Bergamaschini L, et al. Angioedema associated with angiotensin-converting enzyme inhibitor use: outcome after switching to a different treatment. Arch Intern Med 2004;164:910-13.32328 - Abdi R, Dong VM, Lee CJ, et al. Angiotensin II receptor blocker-associated angioedema: on the heels of ACE inhibitor angioedema. Pharmacotherapy 2002;22:1173-5.32329 - Chiu AG, Krowiak EJ, Deeb ZE. Angioedema associated with angiotensin II receptor antagonists: challenging our knowledge of angioedema and its etiology. Laryngoscope 2001;111:1729-31.32330 - Howes LG, Tran D. Can angiotensin receptor antagonists be used safely in patients with previous ACE inhibitor-induced angioedema? Drug Saf 2002;25:73-6.32331 - Kyrmizakis DE, Papadakis CE, Liolios AD, et al. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists. Arch Otolaryngol Head Neck Surg 2004;130:1416-9.32333 - Hyzaar (losartan potassium and hydrochlorothiazide tablets) package insert. White House Station, NJ: Merck & Co., Inc.; 2020 Aug.32380 - Verdel BM, Souverein PC, Egberts AC, et al. Difference in risks of allergic reaction to sulfonamide drugs based on chemical structure. Ann Pharmacother 2006;40:1040-6.32381 - Johnson KK, Green DL, Rife JP, et al. Sulfonamide cross-reactivity: fact or fiction? Ann Pharmacother 2005;39:290-301.32382 - Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. New Engl J Med 2003;349:1628-35.32527 - American Geriatrics Society, British Geriatrics Society, American Academy of Orthopaedic Surgeons Panel on Falls Prevention. Guideline for the prevention of falls in older persons. J Am Geriatr Soc 2001;49:664-72.32528 - Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: II. Cardiac and analgesic drugs. J Am Geriatr Soc 1999;47:40-50.32529 - Poon IO, Braun U. High prevalence of orthostatic hypotension and its correlation with potentially causative medications among elderly veterans. J Clin Pharm Ther 2005;30:173-8.42865 - Amturnide (aliskiren; amlodipine; hydrochlorothiazide) package insert. East Hanover, NJ: Novartis; 2015 Mar.46352 - Begg EJ, Robson RA, Gardiner SJ et al. Quinapril and its metabolite quinaprilat in human milk. Br J Clin Pharmacol 2001;51:478-81.46354 - National Institutes of Health (NIH). Quinapril monograph. LactMed: Drug and Lactation Database. Available at http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~nugSBG:1. Accessed October 24, 2011.46406 - Li D, Yang C, Andrade S, et al. Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study. BMJ 2011;343:d5931.60742 - Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.63903 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin No. 203: Chronic Hypertension in Pregnancy. Obstet Gynecol 2019;133:e23-e50.63923 - The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.64367 - Hoeltzenbein M, Tissen-Diabate T, Fietz AK, et al. Pregnancy outcome after first trimester use of angiotensin AT1 receptor blockers: an observational cohort study. Clin Res Cardiol 2018;107:679-687.

      Mechanism of Action

      The effects of losartan and hydrochlorothiazide on blood pressure are additive. Thiazide diuretics lower the blood pressure by increasing the excretion of sodium; whereas losartan and its principal metabolite lower blood pressure by selectively blocking the AT1 receptor to antagonize the actions of angiotensin II, the primary vasoactive hormone of the renin-angiotensin system. Losartan tends to reverse the hypokalemia caused by the hydrochlorothiazide; this effect is related to the dose of losartan. Due to the dose-related uricosuric effects of losartan, the combination of losartan with hydrochlorothiazide partially attenuates the rise in serum uric acid and the association with hydrochlorothiazide monotherapy.

      • Losartan: Losartan and its longer acting active metabolite (E-3174) are specific and selective AT1 receptor antagonists. While ACE inhibitors inhibit the actions of angiotensin II by preventing its formation from angiotensin I, losartan interferes with the binding of formed angiotensin II to its endogenous receptor. The active metabolite, E-3174, is 10-40 times more potent than losartan and is primarily responsible for the therapeutic effects of losartan. E-3174 directly antagonizes the vasopressor and aldosterone actions of angiotensin II by reversibly and non-competitively binding at the AT1 receptor site. Losartan and its metabolite have no agonist activity at the AT1 receptor. Angiotensin II is the primary vasoactive hormone of the renin-angiotensin system and plays an important role in the pathophysiology of hypertension. Besides being a potent vasoconstrictor, angiotensin II stimulates aldosterone secretion by the adrenal gland. Thus, by blocking the effects of angiotensin II, losartan decreases systemic vascular resistance without a marked change in heart rate. Type 1 angiotensin (AT1) receptors are found in many tissues, including vascular smooth muscle and the adrenal gland. AT2 receptors are also found in many tissues, although their relationship to cardiovascular hemostasis is not known. The affinity of losartan and its metabolite is about 1000-fold greater for the AT1 receptor than for the AT2 receptor. Neither losartan or its metabolite inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels. Losartan therapy is associated with dose-related antiproteinuric effects. Losartan, but not its metabolite, has modest dose-related uricosuric properties; the mechanism of this unique effect is not known.
      • Hydrochlorothiazide, HCTZ: Thiazides increase the excretion of water by inhibiting the reabsorption of sodium and chloride ions at the distal renal tubule. The natriuretic effects are accompanied by a secondary loss of potassium and bicarbonate which can cause a mild hypokalemic, hypochloremic, metabolic alkalosis. Thiazides also decrease the elimination of calcium and uric acid. Thiazides diuretics usually do not affect normal blood pressure. When chronically administered, diuretics decrease peripheral vascular resistance. The exact mechanism responsible for the lowered peripheral resistance is not known; however, excretion of urinary sodium by the kidneys is required to achieve blood pressure reduction. Initially, diuretics lower blood pressure by decreasing cardiac output, plasma volume and extracellular fluid volume. Cardiac output eventually returns to normal, plasma and extracellular fluid values return to slightly less than normal, but peripheral vascular resistance is reduced, resulting in lower blood pressure. Thiazide diuretics also decrease the glomerular filtration rate, which contributes to the drug's lower efficacy in patients with renal impairment. The changes in plasma volume induce an elevation in plasma renin activity and aldosterone secretion which contributes to the potassium losses associated with thiazide diuretics. In general, diuretics can worsen glucose tolerance and lipid abnormalities.
      Revision Date: 08/13/2021, 11:46:23 AM

      References

      Pharmacokinetics

      Losartan; hydrochlorothiazide is administered orally. No pharmacokinetic drug interaction is observed between losartan and hydrochlorothiazide.

      • Losartan: The pharmacokinetics of losartan and its active metabolite are linear over the dose range up to 200 mg; however, the antihypertensive dose-response curve is nonlinear, with proportionally small decreases in blood pressure attained with increased dosage. Losartan and its active metabolite are highly protein bound, mainly to albumin. The free fraction in plasma of losartan is 1.3% and 0.2% for its metabolite. Losartan does not readily penetrate the blood-brain barrier. Approximately 35% an oral dose is renally excreted; overall 4% is excreted unchanged and 6% as metabolite is excreted in the urine. Approximately 60% of a dose is excreted in the feces. The terminal half-life of losartan is 2 hours and 6 hours for its active metabolite in patients without renal impairment.
      • Hydrochlorothiazide, HCTZ: Hydrochlorothiazide crosses the placenta, but not the blood-brain barrier, and is distributed into breast milk. Hydrochlorothiazide is not significantly metabolized and is excreted unchanged in the urine. At least 61% of the oral dose is eliminated unchanged within 24 hours. The elimination half-life ranges from 5.6 to 14.8 hours.

      Route-Specific Pharmacokinetics

      Oral Route

      • Losartan: Losartan is well absorbed, but undergoes substantial first-pass metabolism. The systemic bioavailability is approximately 35%; about 14% of an oral dose is carboxylated in the liver to its active metabolite. Peak serum concentrations occur at 1 hour and 3 to 4 hours, respectively for the parent drug and metabolite. Maximum serum concentrations are similar for losartan and its metabolite, but the AUC for the metabolite is approximately 4 times greater. Food decreases the maximum concentration and slightly (approximately 10%) decreases the AUC. The maximal effects of losartan usually occur within the first week of therapy, although in some studies maximal effect took 3 to 6 weeks.
      • Hydrochlorothiazide, HCTZ: Hydrochlorothiazide absorption from the GI tract varies depending on the formulation, dose, and presence of concomitant disease states. Absorption is reduced in patients with hepatic, cardiac, and/or renal disease. The bioavailability is approximately 60 to 70%.[33476] The onset of action is 2 hours following oral administration, with peak effects occurring at 4 hours. The duration of action ranges from 6 to 12 hours.

      Special Populations

      Hepatic Impairment

      • Losartan: The oral bioavailability is approximately 2 times higher in patients with hepatic impairment. Losartan is metabolized to its active and inactive metabolites by cytochrome P450 2C9 and 3A4. In 1% of patients, less than 1% of the active drug is metabolized to its active metabolite, compared to 14% in the majority of patients. Total plasma clearance of losartan was 50% lower in patients with hepatic impairment, requiring dosage adjustment. Patients with mild to moderate alcoholic cirrhosis demonstrated significantly increased losartan and active metabolite plasma concentrations which were 5 and 1.7 times higher, respectively, compared to normal subjects.
      • Hydrochlorothiazide: The absorption of hydrochlorothiazide is reduced in patients with hepatic disease.

      Renal Impairment

      • Losartan: In patients with renal impairment (creatinine clearances less than 30 mL/minute), AUCs are about 50% greater, and AUCs are doubled in hemodialysis patients. Neither losartan or its active metabolite are removed by hemodialysis. The terminal half-life of losartan is 2 hours and 6 hours for its active metabolite in patients without renal impairment.
      • Hydrochlorothiazide: Results from a study evaluating the pharmacokinetics of hydrochlorothiazide in relation to renal function indicate the elimination half life increases with varying degrees of renal failure, from 6.4 hours for patients with normal renal function to 11.5 hours for patients with mild renal impairment (30 to 90 mL/min) to 20.7 hours in patients with CrCl less than 30 mL/min.[33470]
      Revision Date: 08/13/2021, 11:51:19 AM

      References

      33470 - Neimeyer C, Hasenfuss G, Wais U, et al. Pharmacokinetics of hydrochlorothiazide in relation to renal function. Eur J Clin Pharmacol 1983;24:661-5. Abstract.33476 - Welling PG. Pharmacokinetics of the thiazide diuretics. Biopharm Drug Dispos 1986;7:501-35.

      Pregnancy/Breast-feeding

      pregnancy

      When pregnancy is detected, discontinue losartan; hydrochlorothiazide therapy as soon as possible. Women of child-bearing age should be made aware of the potential risk and losartan; hydrochlorothiazide should only be given after careful counseling and consideration of risks and benefits. When used during the second and third trimesters, drugs that affect the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce fetal renal function and increase fetal and neonatal morbidity and death. Use of drugs that affect the renin-angiotensin system during pregnancy can cause fetal death or injury such as hypotension, neonatal skull hypoplasia, reversible or irreversible renal failure and death. Anhydramnios and oligohydramnios have also been reported. Development of oligohydramnios may be associated with decreased fetal renal function leading to anuria and renal failure and results in fetal limb contractures, craniofacial deformation, hypotension, hypoplastic lung development, and death. [32333] Retrospective data indicate that first trimester use of ACE inhibitors has been associated with a potential risk of birth defects.[32294] However, a much larger observational study (n = 465,754) found that the risk of birth defects was similar in infants exposed to ACE inhibitors during the first trimester, in infants exposed to other antihypertensives during the first trimester, and in those whose mothers were hypertensive but were not treated.[46406] Infants born to mothers with hypertension, either treated or untreated, had a higher risk of birth defects than those born to mothers without hypertension. The authors concluded that the presence of hypertension likely contributed to the development of birth defects rather than the use of medications. An observational cohort study evaluating the outcomes of angiotensin receptor blockers (ARBs) use during the first trimester of pregnancy found an increased rate of major birth defects compared to non-hypertensive pregnancies, 5.4% and 3%, respectively; the difference did not reach statistical significance. The authors noted that there was a higher risk of major birth defects with ARB therapy beyond 6 weeks of gestation compared to discontinuation of ARBs before week 6, 7.3% and 2.8%, respectively. The rates of prematurity and reduced birth weight were also increased in the ARB group. There were no statistically significant differences in the rates of major birth defects, spontaneous abortions, or preterm births between women with chronic hypertension treated with an ARB versus methyldopa.[64367] Thiazide diuretics can cross the placenta resulting in umbilical cord concentrations similar to maternal plasma concentrations and amniotic fluid concentrations that are up to 19 times greater than in the umbilical vein. Based on the results from one large study, first trimester use of thiazide and related diuretics may increase the risk for congenital defects. In addition to malformations, other fetal risks associated with thiazide use during pregnancy include hypoperfusion, fetal or neonatal jaundice, hypoglycemia, thrombocytopenia, hyponatremia, hypokalemia, and death from maternal complications. Once pregnancy is detected, ultrasound examination should be performed if losartan; hydrochlorothiazide exposure occurs beyond the first trimester. In rare cases when another antihypertensive agent cannot be used to treat a pregnant patient, serial ultrasound examinations should be performed to assess the intraamniotic environment. If oligohydramnios is observed, discontinue losartan; hydrochlorothiazide unless it is considered life-saving for the mother. It should be noted that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe newborns with histories of in utero exposure to losartan; hydrochlorothiazide for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, blood pressure and renal perfusion support may be required, as well as exchange transfusion or dialysis to reverse hypotension and/or support decreased renal function.[32333]

      breast-feeding

      According to the manufacturer, because of the potential for adverse effects on the nursing infant, a decision should be made to discontinue breast-feeding or discontinue losartan; hydrochlorothiazide therapy. It is not known whether losartan is excreted into human milk. Hydrochlorothiazide has been detected in human breast milk.[32333] The American Academy of Pediatrics (AAP) has not evaluated the use of losartan in breast-feeding mothers; however, the AAP does consider hydrochlorothiazide to be usually compatible with breast-feeding.[27500] Thiazide diuretics distribute into breast milk, and it has been recommended by some manufacturers that women do not nurse while receiving selected thiazide diuretics. High doses of some thiazide diuretics have been used off-label to suppress lactation, and thus should be used with caution during establishment of breast-feeding. Some experts consider 50 mg or less to be compatible with breast-feeding. The ACE inhibitors captopril, enalapril, benazepril, and quinapril are excreted in human breast milk in very small quantities; therefore, a clinically significant risk to a breast-feeding infant is not expected unless high doses are required.[27500] [29147] [46352] [46354] [63903] If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.[32333]

      Revision Date: 08/13/2021, 01:16:22 PM

      References

      24090 - Freis ED. Critique of the clinical importance of diurectic-induced hypokalemia and elevated cholesterol level. Arch Intern Med 1989;149:2640-8.27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.29147 - Lotensin (benazepril) package insert. Parsippany, NJ: Validus Pharmaceuticals LLC; 2019 Jan.32294 - Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 2006;354:2443-51.32333 - Hyzaar (losartan potassium and hydrochlorothiazide tablets) package insert. White House Station, NJ: Merck & Co., Inc.; 2020 Aug.46352 - Begg EJ, Robson RA, Gardiner SJ et al. Quinapril and its metabolite quinaprilat in human milk. Br J Clin Pharmacol 2001;51:478-81.46354 - National Institutes of Health (NIH). Quinapril monograph. LactMed: Drug and Lactation Database. Available at http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~nugSBG:1. Accessed October 24, 2011.46406 - Li D, Yang C, Andrade S, et al. Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study. BMJ 2011;343:d5931.63903 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin No. 203: Chronic Hypertension in Pregnancy. Obstet Gynecol 2019;133:e23-e50.64367 - Hoeltzenbein M, Tissen-Diabate T, Fietz AK, et al. Pregnancy outcome after first trimester use of angiotensin AT1 receptor blockers: an observational cohort study. Clin Res Cardiol 2018;107:679-687.

      Interactions

      Level 1 (Severe)

      • Cidofovir
      • Dofetilide
      • Tranylcypromine

      Level 2 (Major)

      • Acetaminophen; Dichloralphenazone; Isometheptene
      • Aliskiren
      • Aliskiren; Amlodipine
      • Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
      • Aliskiren; Hydrochlorothiazide, HCTZ
      • Aliskiren; Valsartan
      • Amifostine
      • Amiloride
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      • Amiodarone
      • Angiotensin-converting enzyme inhibitors
      • Cisapride
      • Cocaine
      • Diethylpropion
      • Ephedrine
      • Ephedrine; Guaifenesin
      • Eplerenone
      • Halofantrine
      • Ibritumomab Tiuxetan
      • Idelalisib
      • Lithium
      • Mannitol
      • Mitotane
      • Nesiritide, BNP
      • Non-Ionic Contrast Media
      • Oprelvekin, rh-IL-11
      • Oxymetazoline
      • Porfimer
      • Potassium Phosphate
      • Potassium Phosphate; Sodium Phosphate
      • Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
      • Triamterene
      • Triamterene; Hydrochlorothiazide, HCTZ

      Level 3 (Moderate)

      • Acarbose
      • Acetaminophen; Caffeine; Dihydrocodeine
      • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
      • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
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      • Acetaminophen; Codeine
      • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
      • Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine
      • Acetaminophen; Dextromethorphan; Phenylephrine
      • Acetaminophen; Dextromethorphan; Pseudoephedrine
      • Acetaminophen; Guaifenesin; Phenylephrine
      • Acetaminophen; Hydrocodone
      • Acetaminophen; Oxycodone
      • Acetaminophen; Pentazocine
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      • Acetazolamide
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      • Amobarbital
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      • Amphotericin B
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      • Amyl Nitrite
      • Angiotensin II
      • Apomorphine
      • Aprepitant, Fosaprepitant
      • Arsenic Trioxide
      • Articaine; Epinephrine
      • Asenapine
      • Aspirin, ASA; Butalbital; Caffeine; Codeine
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      • Atracurium
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      • Carbinoxamine; Hydrocodone; Phenylephrine
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      • Carbinoxamine; Phenylephrine
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      • Chlorpheniramine; Dihydrocodeine; Phenylephrine
      • Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
      • Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
      • Chlorpheniramine; Hydrocodone
      • Chlorpheniramine; Hydrocodone; Phenylephrine
      • Chlorpheniramine; Hydrocodone; Pseudoephedrine
      • Chlorpheniramine; Ibuprofen; Pseudoephedrine
      • Chlorpheniramine; Phenylephrine
      • Chlorpheniramine; Pseudoephedrine
      • Chlorpropamide
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      • Dulaglutide
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      • Elvitegravir
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Empagliflozin
      • Empagliflozin; Linagliptin
      • Empagliflozin; Linagliptin; Metformin
      • Empagliflozin; Metformin
      • Enalapril, Enalaprilat
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      • Enalapril; Hydrochlorothiazide, HCTZ
      • Enflurane
      • Epinephrine
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      • Ertugliflozin; Metformin
      • Ertugliflozin; Sitagliptin
      • Escitalopram
      • Esomeprazole
      • Ethanol
      • Etodolac
      • Etomidate
      • Exenatide
      • Famotidine; Ibuprofen
      • Fenoprofen
      • Fentanyl
      • Fexofenadine; Pseudoephedrine
      • Finerenone
      • Fish Oil, Omega-3 Fatty Acids (Dietary Supplements)
      • Fluconazole
      • Fluocinolone; Hydroquinone; Tretinoin
      • Fluoxetine
      • Flurbiprofen
      • Fluvoxamine
      • Fosinopril
      • Fosinopril; Hydrochlorothiazide, HCTZ
      • Fospropofol
      • General anesthetics
      • Glimepiride
      • Glimepiride; Rosiglitazone
      • Glipizide
      • Glipizide; Metformin
      • Glyburide
      • Glyburide; Metformin
      • Granisetron
      • Guaifenesin; Hydrocodone
      • Guaifenesin; Hydrocodone; Pseudoephedrine
      • Guaifenesin; Phenylephrine
      • Guaifenesin; Pseudoephedrine
      • Halobetasol; Tazarotene
      • Haloperidol
      • Halothane
      • Homatropine; Hydrocodone
      • Hydralazine; Isosorbide Dinitrate, ISDN
      • Hydrochlorothiazide, HCTZ; Moexipril
      • Hydrocodone
      • Hydrocodone; Ibuprofen
      • Hydrocodone; Phenylephrine
      • Hydrocodone; Potassium Guaiacolsulfonate
      • Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
      • Hydrocodone; Pseudoephedrine
      • Hydromorphone
      • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
      • Ibuprofen
      • Ibuprofen lysine
      • Ibuprofen; Oxycodone
      • Ibuprofen; Pseudoephedrine
      • Icosapent ethyl
      • Iloperidone
      • Iloprost
      • Inamrinone
      • Incretin Mimetics
      • Indapamide
      • Indomethacin
      • Inotersen
      • Insulin Degludec; Liraglutide
      • Insulin Glargine; Lixisenatide
      • Insulins
      • Intravenous Lipid Emulsions
      • Isavuconazonium
      • Isocarboxazid
      • Isoflurane
      • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
      • Isoniazid, INH; Rifampin
      • Isoproterenol
      • Isosorbide Dinitrate, ISDN
      • Isosorbide Mononitrate
      • Ivacaftor
      • Ketamine
      • Ketoprofen
      • Ketorolac
      • Lansoprazole
      • Lansoprazole; Amoxicillin; Clarithromycin
      • Lansoprazole; Naproxen
      • Lesinurad; Allopurinol
      • Levodopa
      • Levomethadyl
      • Levomilnacipran
      • Levorphanol
      • Lidocaine; Epinephrine
      • Linagliptin
      • Linagliptin; Metformin
      • Liraglutide
      • Lisinopril
      • Lisinopril; Hydrochlorothiazide, HCTZ
      • Lixisenatide
      • Loop diuretics
      • Lopinavir; Ritonavir
      • Loratadine; Pseudoephedrine
      • Lovastatin; Niacin
      • Lumacaftor; Ivacaftor
      • Lumacaftor; Ivacaftor
      • Lurasidone
      • Magnesium Salts
      • Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate
      • Meclofenamate Sodium
      • Mefenamic Acid
      • Meglitinides
      • Meloxicam
      • Meperidine
      • Meperidine; Promethazine
      • Mequinol; Tretinoin
      • Metformin
      • Metformin; Repaglinide
      • Metformin; Rosiglitazone
      • Metformin; Saxagliptin
      • Metformin; Sitagliptin
      • Methadone
      • Methazolamide
      • Methenamine
      • Methenamine; Sodium Acid Phosphate
      • Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
      • Methenamine; Sodium Salicylate
      • Methohexital
      • Methotrexate
      • Methoxsalen
      • Methylphenidate Derivatives
      • Midodrine
      • Miglitol
      • Milnacipran
      • Milrinone
      • Mirtazapine
      • Mivacurium
      • Moexipril
      • Morphine
      • Morphine; Naltrexone
      • Nabumetone
      • Naproxen
      • Naproxen; Esomeprazole
      • Naproxen; Pseudoephedrine
      • Nateglinide
      • Neuromuscular blockers
      • Niacin, Niacinamide
      • Niacin; Simvastatin
      • Nirmatrelvir; Ritonavir
      • Nitrates
      • Nitroglycerin
      • Nitroprusside
      • Nonsteroidal antiinflammatory drugs
      • Norepinephrine
      • Octreotide
      • Olanzapine
      • Olanzapine; Fluoxetine
      • Olanzapine; Samidorphan
      • Oliceridine
      • Ombitasvir; Paritaprevir; Ritonavir
      • Omeprazole
      • Omeprazole; Amoxicillin; Rifabutin
      • Omeprazole; Sodium Bicarbonate
      • Ondansetron
      • Oxaprozin
      • Oxycodone
      • Oxymorphone
      • Paliperidone
      • Pancuronium
      • Pantoprazole
      • Paroxetine
      • Pasireotide
      • Pazopanib
      • Pentamidine
      • Pentazocine
      • Pentazocine; Naloxone
      • Pentoxifylline
      • Perindopril
      • Perindopril; Amlodipine
      • Phendimetrazine
      • Phenelzine
      • Phenobarbital
      • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
      • Phenothiazines
      • Phentermine
      • Phentermine; Topiramate
      • Phenylephrine
      • Photosensitizing agents (topical)
      • Pimozide
      • Pioglitazone
      • Pioglitazone; Glimepiride
      • Pioglitazone; Metformin
      • Piroxicam
      • Polycarbophil
      • Polyethylene Glycol; Electrolytes
      • Polyethylene Glycol; Electrolytes; Ascorbic Acid
      • Potassium
      • Pramlintide
      • Prazosin
      • Prilocaine; Epinephrine
      • Probenecid
      • Probenecid; Colchicine
      • Procainamide
      • Procaine
      • Promethazine; Phenylephrine
      • Propofol
      • Pseudoephedrine
      • Pseudoephedrine; Triprolidine
      • Quetiapine
      • Quinapril
      • Quinapril; Hydrochlorothiazide, HCTZ
      • Quinidine
      • Rabeprazole
      • Ramipril
      • Rapacuronium
      • Rasagiline
      • Remifentanil
      • Repaglinide
      • Rifampin
      • Risperidone
      • Ritonavir
      • Rocuronium
      • Rofecoxib
      • Rosiglitazone
      • Salicylates
      • Saxagliptin
      • Semaglutide
      • Serotonin norepinephrine reuptake inhibitors
      • Sertraline
      • Sevoflurane
      • SGLT2 Inhibitors
      • Silodosin
      • Simvastatin; Sitagliptin
      • Sitagliptin
      • Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous
      • Sodium picosulfate; Magnesium oxide; Anhydrous citric acid
      • Sodium Sulfate; Magnesium Sulfate; Potassium Chloride
      • Spironolactone
      • Spironolactone; Hydrochlorothiazide, HCTZ
      • St. John's Wort, Hypericum perforatum
      • Succinylcholine
      • Sufentanil
      • Sulfacetamide
      • Sulfacetamide; Sulfur
      • Sulfinpyrazone
      • Sulfonylureas
      • Sulindac
      • Sumatriptan; Naproxen
      • Tapentadol
      • Tazarotene
      • Tetrabenazine
      • Tetracaine
      • Tezacaftor; Ivacaftor
      • Thiazolidinediones
      • Thiopental
      • Thiothixene
      • Tirzepatide
      • Tizanidine
      • Tolazamide
      • Tolbutamide
      • Tolmetin
      • Tolvaptan
      • Topiramate
      • Toremifene
      • Tramadol
      • Tramadol; Acetaminophen
      • Trandolapril
      • Trandolapril; Verapamil
      • Treprostinil
      • Tretinoin, ATRA
      • Tretinoin; Benzoyl Peroxide
      • Trimethoprim
      • Tubocurarine
      • Valdecoxib
      • Vecuronium
      • Vemurafenib
      • Venlafaxine
      • Verteporfin
      • Vilazodone
      • Vitamin D
      • Vitamin D
      • Vitamin D analogs
      • Vorinostat
      • Vortioxetine
      • Yohimbine
      • Ziconotide
      • Ziprasidone

      Level 4 (Minor)

      • Aclidinium; Formoterol
      • Albuterol
      • Alprostadil
      • Amphetamine; Dextroamphetamine Salts
      • Anticholinergics
      • Apraclonidine
      • Arformoterol
      • Aripiprazole
      • Atazanavir
      • Atazanavir; Cobicistat
      • Atropine
      • Atropine; Difenoxin
      • Atropine; Edrophonium
      • Benzphetamine
      • Benztropine
      • Beta-agonists
      • Budesonide; Formoterol
      • Budesonide; Glycopyrrolate; Formoterol
      • Chlordiazepoxide; Clidinium
      • Cobicistat
      • Darunavir
      • Darunavir; Cobicistat
      • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
      • Delavirdine
      • Dicyclomine
      • Diphenoxylate; Atropine
      • Donepezil; Memantine
      • Efavirenz
      • Efavirenz; Emtricitabine; Tenofovir
      • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
      • Elbasvir; Grazoprevir
      • Erythromycin
      • Erythromycin; Sulfisoxazole
      • Estradiol
      • Estradiol Cypionate; Medroxyprogesterone
      • Fenofibric Acid
      • Flavoxate
      • Fluticasone; Salmeterol
      • Fluticasone; Umeclidinium; Vilanterol
      • Fluticasone; Vilanterol
      • Formoterol
      • Formoterol; Mometasone
      • Fosphenytoin
      • Glycopyrrolate
      • Glycopyrrolate; Formoterol
      • Hyoscyamine
      • Imatinib
      • Indacaterol
      • Indacaterol; Glycopyrrolate
      • Ipratropium; Albuterol
      • Levalbuterol
      • Lisdexamfetamine
      • Memantine
      • Mepenzolate
      • Mestranol; Norethindrone
      • Metaproterenol
      • Methamphetamine
      • Methscopolamine
      • Metoclopramide
      • Nefazodone
      • Olodaterol
      • Oxybutynin
      • Phenytoin
      • Pirbuterol
      • Propantheline
      • Salmeterol
      • Scopolamine
      • Solifenacin
      • Streptozocin
      • Sulfonamides
      • Tegaserod
      • Terbutaline
      • Tiotropium; Olodaterol
      • Tolterodine
      • Trazodone
      • Trihexyphenidyl
      • Trospium
      • Umeclidinium; Vilanterol
      • Vigabatrin
      • Voriconazole
      • Zafirlukast
      Acarbose: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. [33489] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. [29179] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Acetaminophen; Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [33654] Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended. [7820] (Moderate) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended. [31048] Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Acetaminophen; Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] Acetaminophen; Oxycodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [60634] Acetaminophen; Pentazocine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [30219] Acetaminophen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Acetazolamide: (Moderate) Acetazolamide promotes electrolyte excretion including hydrogen ions, sodium, and potassium. It can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy. [28294] [30754] [50999] Acetohexamide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Aclidinium; Formoterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Acrivastine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Albiglutide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Albuterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Aldesleukin, IL-2: (Moderate) Angiotensin II receptor antagonists may potentiate the hypotension seen with aldesleukin, IL 2. [41853] (Moderate) Thiazide diuretics may potentiate the hypotension seen with aldesleukin, IL 2. [41853] Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents. [27942] Alendronate; Cholecalciferol: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. [27970] [30166] [34775] [60895] Alfentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with alfentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [30072] Aliskiren: (Major) Aliskiren-containing products are contraindicated in combination with angiotensin II receptor antagonists (ARBs) in patients with diabetes mellitus. In general, avoid combined use of two renin-angiotensin-aldosterone system (RAAS) inhibitors, particularly in patients with CrCl less than 60 mL/minute. Combination therapy increases the risk for hyperkalemia, renal impairment, hypotension, and other side effects. Most patients receiving a comination of two RAAS inhibitors, such as ARBs and aliskiren, do not obtain any additional benefit compared to monotherapy. Closely monitor blood pressure, renal function, and electrolytes if aliskiren must be combined with another RAAS inhibitor. In the ALTITUDE trial, patients with type 2 diabetes and renal impairment, a population at high risk for cardiovascular and renal events, were given aliskiren in addition to ACE inhibitors or ARBs. The trial was stopped early because aliskiren was associated with an increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension. In the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, no additional benefit over monotherapy was seen in patients receiving the combination of losartan and lisinopril compared to monotherapy; however, there was an increased incidence of hyperkalemia and acute renal injury. [29130] [29132] [32198] [33200] [60860] [63923] Aliskiren; Amlodipine: (Major) Aliskiren-containing products are contraindicated in combination with angiotensin II receptor antagonists (ARBs) in patients with diabetes mellitus. In general, avoid combined use of two renin-angiotensin-aldosterone system (RAAS) inhibitors, particularly in patients with CrCl less than 60 mL/minute. Combination therapy increases the risk for hyperkalemia, renal impairment, hypotension, and other side effects. Most patients receiving a comination of two RAAS inhibitors, such as ARBs and aliskiren, do not obtain any additional benefit compared to monotherapy. Closely monitor blood pressure, renal function, and electrolytes if aliskiren must be combined with another RAAS inhibitor. In the ALTITUDE trial, patients with type 2 diabetes and renal impairment, a population at high risk for cardiovascular and renal events, were given aliskiren in addition to ACE inhibitors or ARBs. The trial was stopped early because aliskiren was associated with an increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension. In the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, no additional benefit over monotherapy was seen in patients receiving the combination of losartan and lisinopril compared to monotherapy; however, there was an increased incidence of hyperkalemia and acute renal injury. [29130] [29132] [32198] [33200] [60860] [63923] Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Major) Aliskiren-containing products are contraindicated in combination with angiotensin II receptor antagonists (ARBs) in patients with diabetes mellitus. In general, avoid combined use of two renin-angiotensin-aldosterone system (RAAS) inhibitors, particularly in patients with CrCl less than 60 mL/minute. Combination therapy increases the risk for hyperkalemia, renal impairment, hypotension, and other side effects. Most patients receiving a comination of two RAAS inhibitors, such as ARBs and aliskiren, do not obtain any additional benefit compared to monotherapy. Closely monitor blood pressure, renal function, and electrolytes if aliskiren must be combined with another RAAS inhibitor. In the ALTITUDE trial, patients with type 2 diabetes and renal impairment, a population at high risk for cardiovascular and renal events, were given aliskiren in addition to ACE inhibitors or ARBs. The trial was stopped early because aliskiren was associated with an increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension. In the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, no additional benefit over monotherapy was seen in patients receiving the combination of losartan and lisinopril compared to monotherapy; however, there was an increased incidence of hyperkalemia and acute renal injury. [29130] [29132] [32198] [33200] [60860] [63923] Aliskiren; Hydrochlorothiazide, HCTZ: (Major) Aliskiren-containing products are contraindicated in combination with angiotensin II receptor antagonists (ARBs) in patients with diabetes mellitus. In general, avoid combined use of two renin-angiotensin-aldosterone system (RAAS) inhibitors, particularly in patients with CrCl less than 60 mL/minute. Combination therapy increases the risk for hyperkalemia, renal impairment, hypotension, and other side effects. Most patients receiving a comination of two RAAS inhibitors, such as ARBs and aliskiren, do not obtain any additional benefit compared to monotherapy. Closely monitor blood pressure, renal function, and electrolytes if aliskiren must be combined with another RAAS inhibitor. In the ALTITUDE trial, patients with type 2 diabetes and renal impairment, a population at high risk for cardiovascular and renal events, were given aliskiren in addition to ACE inhibitors or ARBs. The trial was stopped early because aliskiren was associated with an increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension. In the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, no additional benefit over monotherapy was seen in patients receiving the combination of losartan and lisinopril compared to monotherapy; however, there was an increased incidence of hyperkalemia and acute renal injury. [29130] [29132] [32198] [33200] [60860] [63923] Aliskiren; Valsartan: (Major) Aliskiren-containing products are contraindicated in combination with angiotensin II receptor antagonists (ARBs) in patients with diabetes mellitus. In general, avoid combined use of two renin-angiotensin-aldosterone system (RAAS) inhibitors, particularly in patients with CrCl less than 60 mL/minute. Combination therapy increases the risk for hyperkalemia, renal impairment, hypotension, and other side effects. Most patients receiving a comination of two RAAS inhibitors, such as ARBs and aliskiren, do not obtain any additional benefit compared to monotherapy. Closely monitor blood pressure, renal function, and electrolytes if aliskiren must be combined with another RAAS inhibitor. In the ALTITUDE trial, patients with type 2 diabetes and renal impairment, a population at high risk for cardiovascular and renal events, were given aliskiren in addition to ACE inhibitors or ARBs. The trial was stopped early because aliskiren was associated with an increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension. In the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, no additional benefit over monotherapy was seen in patients receiving the combination of losartan and lisinopril compared to monotherapy; however, there was an increased incidence of hyperkalemia and acute renal injury. [29130] [29132] [32198] [33200] [60860] [63923] Allopurinol: (Moderate) The occurrence of certain hypersensitivity reactions may be increased in patients with renal impairment who receive allopurinol and thiazide diuretics in combination. The precise mechanism for such events is unclear but likely immune-mediated and may be related to an effect of oxypurinol; elevated oxypurinol concentrations appear to be associated with hypersensitivity reactions; decreased clearance of this metabolite may occur with renal impairment and with the concurrent use of thiazide diuretics. Severe skin reactions include exfoliative dermatitis, toxic epidermal necrolysis and Steven's Johnson syndrome; some reactions have been fatal. In addition, thiazide diuretics, like hydrochlorothiazide, can cause hyperuricemia. Since thiazides reduce the clearance of uric acid, patients with gout or hyperuricemia may have exacerbations of their disease. [28048] [33874] [40304] Alogliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Alogliptin; Metformin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Alogliptin; Pioglitazone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Alpha-glucosidase Inhibitors: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. [33489] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as angiotensin II receptor antagonists (angiotensin receptor blockers, or ARBs), may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil. [30847] [30849] [55990] (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as thiazide diuretics, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil. [30847] [30849] [55990] Amifostine: (Major) Patients receiving angiotensin II receptor antagonists should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine. [49124] (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses. [5937] Amiloride: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients. [29135] [43532] [60860] Amiloride; Hydrochlorothiazide, HCTZ: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients. [29135] [43532] [60860] Aminolevulinic Acid: (Moderate) Thiazide diuretics may cause photosensitivity and may increase the photosensitization effects of photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin. [29179] [30713] Amiodarone: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics. [3085] [4950] [6115] (Minor) Coadministration of losartan with amiodarone may result in increased exposure to losartan but decreased concentrations of the active metabolite. The conversion of losartan to its active metabolite is primarily mediated by CYP2C9; amiodarone is an inhibitor of CYP2C9. When coadministered with another inhibitor of CYP2C9, the AUC of the active metabolite of losartan was decreased by 40%, but the AUC of losartan increased by 70%. [27491] [28608] [28896] Amlodipine; Benazepril: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Amlodipine; Celecoxib: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration. [6532] Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [43594] Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. [29332] [53320] [60070] (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. [29332] [31563] [46053] [60070] [60232] Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [28333] [29179] Amphotericin B lipid complex (ABLC): (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [28333] [29179] Amphotericin B liposomal (LAmB): (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [28333] [29179] Amphotericin B: (Moderate) The risk of developing severe hypokalemia can be increased when amphotericin B is coadministered with thiazide diuretics. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [28333] [29179] Amyl Nitrite: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29206] [29386] (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29386] [29551] Angiotensin II: (Moderate) Angiotensin II receptor antagonists (angiotensin receptor blockers, or ARBs) may decrease the response to angiotensin II. Angiotensin II is a naturally occurring peptide hormone of the renin-angiotensin-aldosterone system (RAAS) that causes vasoconstriction and an increase in blood pressure. ARBs block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the angiotensin receptor in many tissues. [62722] Angiotensin-converting enzyme inhibitors: (Major) Most patients receiving the combination of two renin-angiotensin-aldosterone system (RAAS) inhibitors, such as angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor antagonists (ARBs) do not obtain any additional benefit compared to monotherapy. Combination therapy has been associated with an increased risk of diarrhea, hypotension, syncope, hyperkalemia, and renal dysfunction resulting in dialysis, doubling of serum creatinine, and death in clinical studies. The risk of hyperkalemia is particularly high in patients with renal impairment (stage 3a or higher kidney disease). In general, avoid combined use of these drugs together. Patients who must receive concomitant therapy with ACE inhibitors and ARBs should be closely monitored for renal dysfunction, hypotension, and hyperkalemia. Closely monitor blood pressure, renal function, and electrolytes. [27991] [28608] [29147] [34997] [34998] [63923] (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Anticholinergics: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Apomorphine: (Moderate) Use of angiotensin II receptor antagonists and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination. [28661] (Moderate) Use of thiazide diuretics and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination. [28661] Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically. [6224] Aprepitant, Fosaprepitant: (Moderate) Use caution if losartan and aprepitant, fosaprepitant are used concurrently, and monitor for an increase in losartan-related adverse effects for several days after administration of a multi-day aprepitant regimen. Losartan is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of losartan. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Aprepitant is also a CYP2C9 inducer and losartan is a CYP2C9 substrate. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. [28608] [30676] [40027] Arformoterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. [31327] Arsenic Trioxide: (Moderate) Concomitant use of thiazide diuretics and arsenic trioxide should be done cautiously. Electrolyte abnormalities, such as hypokalemia and hypomagnesemia, may increase the risk for QT prolongation and torsade de pointes. [26417] [59438] Articaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known. [36343] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [33654] Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. [29179] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [33654] Aspirin, ASA; Omeprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [43594] Aspirin, ASA; Oxycodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [60634] Atazanavir: (Minor) Caution is warranted when atazanavir is administered with losartan as there is a potential for elevated losartan concentrations. Losartan is a substrate of CYP3A4; atazanavir is an inhibitor of CYP3A4. [28142] [28608] Atazanavir; Cobicistat: (Minor) Caution is warranted when atazanavir is administered with losartan as there is a potential for elevated losartan concentrations. Losartan is a substrate of CYP3A4; atazanavir is an inhibitor of CYP3A4. [28142] [28608] (Minor) Caution is warranted when cobicistat is administered with losartan as there is a potential for increased losartan concentrations. Losartan is a substrate of CYP3A4; cobicistat is an inhibitor of CYP3A4. [28608] [51664] [58000] Atracurium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane. [52452] [52503] [65487] Atropine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. [40708] (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Atropine; Difenoxin: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Atropine; Edrophonium: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required. [30582] [57272] Barbiturates: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. [29179] Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Phenobarbital causes a reduction of approximately 20 percent in the AUC of losartan and its metabolite. The clinical significance of this interaction is unknown. [28608] (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Belladonna; Opium: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with opium. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [57409] (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Benazepril: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Benzhydrocodone; Acetaminophen: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with benzhydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [62889] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. [40708] (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Benzphetamine: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. [28456] (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. [28456] [28477] Benztropine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Beta-agonists: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Boceprevir: (Moderate) Close clinical monitoring is advised when administering losartan with boceprevir due to an increased potential for losartan-related adverse events. If losartan dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of losartan. Losartan is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated losartan plasma concentrations. [44314] [5339] Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients. [5113] Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. [59949] Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Brompheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Brompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Budesonide; Formoterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Budesonide; Glycopyrrolate; Formoterol: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Bupivacaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Bupivacaine; Meloxicam: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Buprenorphine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with buprenorphine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [41235] [55234] [60826] Buprenorphine; Naloxone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with buprenorphine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [41235] [55234] [60826] Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [33654] Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including angiotensin II receptor antagonists. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure. [27964] (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including thiazide diuretics. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure. [27964] Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as angiotensin II receptor antagonists, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. [32159] [32160] (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. [32159] [32160] Calcium: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended. [29179] Calcium; Vitamin D: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. [27970] [30166] [34775] [60895] Canagliflozin: (Moderate) When canagliflozin is initiated in patients already receiving diuretics, symptomatic hypotension can occur. Patients with impaired renal function (eGFR < 60 ml/min/1.73 m2), low systolic blood pressure, or who are elderly may also be at a greater risk. Before initiating canagliflozin in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. In addition, thiazide diuretics, can also decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. Thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients receiving canagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Canagliflozin; Metformin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) When canagliflozin is initiated in patients already receiving diuretics, symptomatic hypotension can occur. Patients with impaired renal function (eGFR < 60 ml/min/1.73 m2), low systolic blood pressure, or who are elderly may also be at a greater risk. Before initiating canagliflozin in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. In addition, thiazide diuretics, can also decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. Thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients receiving canagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Captopril: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Carbamazepine: (Moderate) Both thiazide diuretics and carbamazepine are associated with hyponatremia. Coadministration may result in an additive risk of developing hyponatremia. When concurrent therapy with a thiazide diuretic and carbamazepine is necessary, monitor patients for hyponatremia. [34270] [34271] Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Carbetapentane; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Carbetapentane; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. [28521] (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. [5251] Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. [28521] (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. [5251] Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Carbinoxamine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Carbinoxamine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Cardiac glycosides: (Moderate) Thiazide diuretics can cause hypokalemia, hypomagnesemia, or hypercalcemia which may increase digoxin's pharmacologic effect. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity. It is also recommended that serum potassium, magnesium, and calcium be monitored regularly in patients receiving digoxin. [26417] [28272] [28489] Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs. [60164] Celecoxib: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Celecoxib; Tramadol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with tramadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [28314] (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Cetirizine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Chlordiazepoxide; Clidinium: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. [28996] Chlorpheniramine; Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [33654] Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. [29179] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. [29179] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Chlorpheniramine; Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Chlorpheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Chlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Chlorpropamide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Cholestyramine: (Moderate) Cholestyramine, an ion exchange resin, binds hydrochlorothiazide and reduces its absorption from the gastrointestinal tract by up to 85% when co-administered as single doses. Although the manufacturer for Questran recommends that other medicines be taken at least 1 hour before or 4-6 hours after cholestyramine, it has been recommended that thiazides be administered at least 4 hours before or after cholestyramine to minimize the reduction in absorption. By administering hydrochlorothiazide at least 4 hours before cholestyramine, the decrease in absorption of hydrochlorothiazide is approximately 30-35%. [28070] [29179] [29414] [29415] Cidofovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir. [28388] Cisapride: (Major) Cisapride should be used with great caution in patients receiving thiazide diuretics. Drugs that are associated with depletion of electrolytes may cause cisapride-induced cardiac arrhythmias. Serum electrolytes and creatinine should be assessed prior to administration of cisapride and whenever conditions develop that may affect electrolyte imbalance or renal function. [28407] [28978] Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane. [52452] [52503] [65487] Citalopram: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia. [28269] Clindamycin; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. [28570] Clozapine: (Moderate) Caution is advisable during concurrent use of clozapine and thiazide diuretics as concurrent use may increase the risk and severity of hypotension. In addition, electrolyte imbalance caused by thiazide diuretics may increase the risk of QT prolongation by clozapine. [28262] [29397] (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug. [28262] Cobicistat: (Minor) Caution is warranted when cobicistat is administered with losartan as there is a potential for increased losartan concentrations. Losartan is a substrate of CYP3A4; cobicistat is an inhibitor of CYP3A4. [28608] [51664] [58000] Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation. [6289] Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [33654] Codeine; Guaifenesin: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [33654] Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [33654] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [33654] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Codeine; Promethazine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [33654] Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10. [34900] Colestipol: (Moderate) Although to a lesser extent than cholestyramine, colestipol also has been shown to inhibit the GI absorption and therapeutic response of thiazide diuretics. Single doses of colestipol resins reduce the absorption of HCTZ by up to 43%. Administering thiazide diuretics at least 2 hours before colestipol has been suggested to minimize the interaction. [28071] [29179] [29414] Corticosteroids: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Cosyntropin: (Moderate) Use cosyntropin cautiously in patients receiving diuretics. Cosyntropin may accentuate the electrolyte loss associated with diuretic therapy. [43709] Cyclophosphamide: (Moderate) Closely monitor complete blood counts if coadministration of cyclophosphamide with thiazide diuretics is necessary as there is an increased risk of hematologic toxicity and immunosuppression. [65780] [65781] [65782] Cyclosporine: (Moderate) Coadministration of cyclosporine and an angiotensin II receptor antagonist, like losartan, may increase the risk of hyperkalemia and reduced renal function. In response to cyclosporine-induced renal afferent vasoconstriction and glomerular hypoperfusion, angiotensin II is required to maintain an adequate glomerular filtration rate. Inhibition of angiotensin-converting enzyme (ACE) could reduce renal function acutely. Several cases of acute renal failure have been associated with the addition of enalapril to cyclosporine therapy in renal transplant patients. Also, cyclosporine can cause hyperkalemia, and inhibition of angiotensin II leads to reduced aldosterone concentrations, which can increase the serum potassium concentration. Closely monitor renal function and serum potassium concentrations in patients receiving cyclosporine concurrently with losartan. [28404] [29323] [29324] [39870] Dabrafenib: (Moderate) The concomitant use of dabrafenib, a CYP29 inducer and losartan, a CYP2C9 substrate, may result in decreased levels of losartan; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for loss of losartan efficacy. [5339] [54802] Dapagliflozin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Dapagliflozin; Metformin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Dapagliflozin; Saxagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Darunavir: (Minor) Caution is warranted when darunavir is administered with losartan as there is a potential for elevated losartan concentrations. Losartan is a substrate of CYP3A4; darunavir is an inhibitor of CYP3A4. [28608] [32432] Darunavir; Cobicistat: (Minor) Caution is warranted when cobicistat is administered with losartan as there is a potential for increased losartan concentrations. Losartan is a substrate of CYP3A4; cobicistat is an inhibitor of CYP3A4. [28608] [51664] [58000] (Minor) Caution is warranted when darunavir is administered with losartan as there is a potential for elevated losartan concentrations. Losartan is a substrate of CYP3A4; darunavir is an inhibitor of CYP3A4. [28608] [32432] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Minor) Caution is warranted when cobicistat is administered with losartan as there is a potential for increased losartan concentrations. Losartan is a substrate of CYP3A4; cobicistat is an inhibitor of CYP3A4. [28608] [51664] [58000] (Minor) Caution is warranted when darunavir is administered with losartan as there is a potential for elevated losartan concentrations. Losartan is a substrate of CYP3A4; darunavir is an inhibitor of CYP3A4. [28608] [32432] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of losartan with ritonavir may result in elevated losartan plasma concentrations. Losartan is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together. [47165] [5339] [58664] Delavirdine: (Minor) Inhibitors of the hepatic CYP2C9 isoenzyme, such as delavirdine, have potential to inhibit the conversion of losartan to its active metabolite E-3174. The importance of theoretical CYP2C9 interactions has not been established; monitor therapeutic response to individualize losartan dosage. [4718] Desloratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Desvenlafaxine: (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia. [11625] [28275] [29934] [34940] [55469] Dexbrompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Dexlansoprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [43594] Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension. [28249] Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving beta-blockers, hydralazine, methyldopa, minoxidil, nitrites, prazosin, reserpine, or other antihypertensive agents. [29537] (Moderate) Enhanced hyperglycemia is possible during concurrent use of diazoxide and thiazide diuretics. Additive hypotensive effects can also occur with the concomitant administration of diazoxide with thiazide diuretics. [29537] Dichlorphenamide: (Moderate) Use dichlorphenamide and diuretics together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including loop diuretics and thiazide diuretics. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy. [60122] Diclofenac: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Diclofenac; Misoprostol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Dicyclomine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Diethylpropion: (Major) Diethylpropion has vasopressor effects and may limit the benefit of thiazide diuretics. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications. [5851] (Moderate) Diethylpropion has vasopressor effects and may limit the benefit of angiotensin II receptor antagonists. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications. [29114] Diflunisal: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Digitoxin: (Moderate) Thiazide diuretics can cause hypokalemia, hypomagnesemia, or hypercalcemia which may increase digoxin's pharmacologic effect. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity. It is also recommended that serum potassium, magnesium, and calcium be monitored regularly in patients receiving digoxin. [26417] [28272] [28489] Digoxin: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity. [28272] (Moderate) Thiazide diuretics can cause hypokalemia, hypomagnesemia, or hypercalcemia which may increase digoxin's pharmacologic effect. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity. It is also recommended that serum potassium, magnesium, and calcium be monitored regularly in patients receiving digoxin. [26417] [28272] [28489] Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. [29179] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Diphenhydramine; Ibuprofen: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Diphenhydramine; Naproxen: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Diphenoxylate; Atropine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Dobutamine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives such as metolazone when administered concomitantly. [6234] Dofetilide: (Contraindicated) Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for dofetilide-induced torsade de pointes. Additionally, in patients treated with either hydrochlorothiazide 50 mg or hydrochlorothiazide/triamterene 50 mg/100 mg daily in combination with dofetilide 500 mcg twice daily for 5 days, dofetilide AUC and Cmax concentrations increased by 27% and 21%, respectively, for the hydrochlorothiazide alone group and by 30% and 16%, respectively, for the hydrochlorothiazide/triamterene group. Furthermore, a 197% and 190% QTc increase over time was seen in the hydrochlorothiazide and hydrochlorothiazide/triamterene groups, respectively. Based on these findings, the manufacturer of dofetilide contraindicates the concomitant use of hydrochlorothiazide (alone or in combination with other drugs such as triamterene); these findings can be explained both by an increase in the plasma concentration of dofetilide and a reduction in the serum potassium concentration. In a population pharmacokinetic analysis of plasma dofetilide concentrations, the mean dofetilide clearance of dofetilide was 16% lower in patients on thiazide diuretics. It is prudent to avoid the use of any thiazide diuretic in combination with dofetilide. [26417] [28221] Dolasetron: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron. [28308] Donepezil; Memantine: (Minor) Memantine reduced the bioavailability of hydrochlorothiazide by roughly 20% in a drug interaction study. The clinical significance of this pharmacokinetic interaction, if any, is unknown. [5905] [8204] Dopamine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives such as metolazone when administered concomitantly. [6234] Doxacurium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane. [52452] [52503] [65487] Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A. Losartan is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution. [36101] Droperidol: (Moderate) Caution is advised when using droperidol in combination with thiazide diuretics which may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias. [28737] Drospirenone: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function. [31698] [40219] [41929] [42068] [42851] Drospirenone; Estetrol: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function. [31698] [40219] [41929] [42068] [42851] Drospirenone; Estradiol: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function. [31698] [40219] [41929] [42068] [42851] Drospirenone; Ethinyl Estradiol: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function. [31698] [40219] [41929] [42068] [42851] Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of angiotensin II receptor antagonists (ARBs) may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if ARBs are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function. [31698] [40219] [41929] [42068] [42851] Dulaglutide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. Monitor blood pressure if the combination is necessary. [29934] (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia. [11625] [28275] [29934] [34940] [55469] Efavirenz: (Minor) Efavirenz inhibits CYP2C9 and CYP2C19 and may inhibit the metabolism of drugs that are substrates for CYP2C9 or CYP2C19 including losartan. [4718] [5172] Efavirenz; Emtricitabine; Tenofovir: (Minor) Efavirenz inhibits CYP2C9 and CYP2C19 and may inhibit the metabolism of drugs that are substrates for CYP2C9 or CYP2C19 including losartan. [4718] [5172] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Efavirenz inhibits CYP2C9 and CYP2C19 and may inhibit the metabolism of drugs that are substrates for CYP2C9 or CYP2C19 including losartan. [4718] [5172] Elbasvir; Grazoprevir: (Minor) Administering losartan with grazoprevir may result in elevated losartan plasma concentrations. Losartan is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events. [28608] [60523] Elexacaftor; tezacaftor; ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as losartan. Ivacaftor is an inhibitor of CYP3A and a weak inhibitor of CYP2C9; losartan is metabolized by CYP3A and CYP2C9. Co-administration of ivacaftor with CYP3A and CYP2C9 substrates,such as losartan, can theoretically increase losartan exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined. [28608] [48524] Elvitegravir: (Moderate) Caution is warranted when elvitegravir is administered with losartan as there is a potential for decreased losartan concentrations. Losartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer. [28608] [51664] [58001] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when elvitegravir is administered with losartan as there is a potential for decreased losartan concentrations. Losartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer. [28608] [51664] [58001] (Minor) Caution is warranted when cobicistat is administered with losartan as there is a potential for increased losartan concentrations. Losartan is a substrate of CYP3A4; cobicistat is an inhibitor of CYP3A4. [28608] [51664] [58000] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when elvitegravir is administered with losartan as there is a potential for decreased losartan concentrations. Losartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer. [28608] [51664] [58001] (Minor) Caution is warranted when cobicistat is administered with losartan as there is a potential for increased losartan concentrations. Losartan is a substrate of CYP3A4; cobicistat is an inhibitor of CYP3A4. [28608] [51664] [58000] Empagliflozin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Empagliflozin; Linagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Empagliflozin; Linagliptin; Metformin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Empagliflozin; Metformin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Enalapril, Enalaprilat: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Enalapril; Felodipine: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Enflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. [28325] Ephedrine: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by thiazide diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. [26181] [29548] (Moderate) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. [26181] [29548] Ephedrine; Guaifenesin: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by thiazide diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. [26181] [29548] (Moderate) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. [26181] [29548] Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Eplerenone: (Major) Monitor serum potassium and serum creatinine concentrations within 3 to 7 days of initiating coadministration of eplerenone and angiotensin II receptor antagonists (ARBs). Hyperkalemia risk is increased when eplerenone is used with ARBs. Patients who develop hyperkalemia may continue eplerenone with proper dose adjustment; eplerenone dose reduction decreases potassium concentrations. [27990] Epoprostenol: (Moderate) Angiotensin II receptor antagonists can enhance the hypotensive effects of antihypertensive agents if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. [4892] Ertugliflozin; Metformin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Ertugliflozin; Sitagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Erythromycin: (Minor) Losartan is metabolized to an active metabolite E-3174. The AUC of this active metabolite of oral losartan is not affected by erythromycin, a CYP3A4 inhibitor; however, the AUC of losartan is increased by 30%. [5339] Erythromycin; Sulfisoxazole: (Minor) Losartan is metabolized to an active metabolite E-3174. The AUC of this active metabolite of oral losartan is not affected by erythromycin, a CYP3A4 inhibitor; however, the AUC of losartan is increased by 30%. [5339] Escitalopram: (Moderate) Patients receiving a diuretic during treatment with escitalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of escitalopram should be considered in patients who develop symptomatic hyponatremia. [28270] Esomeprazole: (Moderate) Proton pump inhibitors, such as esomeprazole, have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [29524] [43594] Estradiol Cypionate; Medroxyprogesterone: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored for antihypertensive effectiveness. [805] (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness. [805] Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored for antihypertensive effectiveness. [805] (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness. [805] Ethanol: (Moderate) Patients should be cautioned that ingesting alcohol can increase the chance of low blood pressure and dizziness when taking a thiazide diuretic or the related drug, metolazone. Patients may wish to limit alcohol ingestion while taking one of these diuretics and should be monitored for signs or symptoms of hypotension, including postural hypotension and dizziness. [29179] [29397] [46260] [48546] [48850] [51396] [52261] [52335] Etodolac: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. [28325] Exenatide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Famotidine; Ibuprofen: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as losartan, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of losartan during coadministration with fenofibric acid. [49952] [5339] Fenoprofen: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Fentanyl: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with fentanyl. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29623] [29763] [32731] [40943] Fexofenadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Finerenone: (Moderate) Monitor serum potassium concentrations closely if finerenone and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia. [28608] [29134] [60860] [66793] Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. [30536] [30537] [30538] [30539] [30540] Flavoxate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Fluconazole: (Moderate) Hydrochlorothiazide may decrease the renal clearance of fluconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n=13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. There was a mean +/- SD increase in fluconazole AUC and Cmax of 45 +/- 31% and 43 +/- 31%, respectively. These changes are attributed to a mean +/- SD reduction in fluconazole renal clearance of 30% +/- 12%. [28674] [42865] (Moderate) Inhibitors of the hepatic CYP2C9 isoenzyme have potential to inhibit the conversion of losartan to its active metabolite E-3174. Fluconazole has been shown to increase the AUC of losartan and E-3174 by 69% and 41%, respectively. Monitor therapeutic response to individualize losartan dosage. [4192] Fluocinolone; Hydroquinone; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. [28570] Fluoxetine: (Moderate) Patients receiving a diuretic during treatment with fluoxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluoxetine should be considered in patients who develop symptomatic hyponatremia. [32127] (Minor) Inhibitors of the hepatic CYP2C9 isoenzyme, such as fluoxetine, have potential to inhibit the conversion of losartan to its active metabolite. Monitor therapeutic response to individualize losartan dosage. [4192] Flurbiprofen: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Fluticasone; Salmeterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Fluticasone; Umeclidinium; Vilanterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Fluticasone; Vilanterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Fluvoxamine: (Moderate) Inhibitors of the hepatic CYP2C9 isoenzyme, such as fluvoxamine, have the potential to inhibit the conversion of losartan, a prodrug, to its active metabolite. No specific management recommendations are currently available. Monitor therapeutic response to individualize losartan dosage to desired blood pressure or other therapeutic goals. [27491] [28608] [62559] (Moderate) Patients receiving a diuretic during treatment with fluvoxamine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/L have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluvoxamine should be considered in patients who develop symptomatic hyponatremia. [47184] [50507] Formoterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Formoterol; Mometasone: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Fosinopril: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Fosphenytoin: (Minor) In a study of 16 healthy volunteers, phenytoin inhibited the CYP2C9-mediated conversion of losartan to its active metabolite. The clinical significance of this interaction is not known; however, a reduced clinical effect of losartan is possible via reduced formation of a metabolite which significantly contributes to the efficacy of losartan. A similar interaction might be expected with fosphenytoin. [4060] Fospropofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. [28325] General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. [28325] Glimepiride: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Glimepiride; Rosiglitazone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Glipizide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Glipizide; Metformin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Glyburide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Glyburide; Metformin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Glycopyrrolate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Glycopyrrolate; Formoterol: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Granisetron: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias. [31723] Guaifenesin; Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Halobetasol; Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. [28587] [28588] Halofantrine: (Major) Due to the risks of cardiac toxicity of halofantrine in patients with hypokalemia and/or hypomagnesemia, the use of halofantrine should be avoided when feasible in those patients receiving thiazide diuretics. Electrolyte imbalances may occur while on these diuretics, which may in turn predispose patients to the cardiac effects of halofantrine. [26417] [28241] Haloperidol: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. [28307] (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. [5036] Halothane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. [28325] Homatropine; Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29206] [29386] (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29386] [29551] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] Hydrocodone; Ibuprofen: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Hydrocodone; Phenylephrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Hydromorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with hydromorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [39635] Hyoscyamine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. [40708] (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Ibritumomab Tiuxetan: (Major) Avoid coadministration of potassium phosphate and angiotensin II receptor antagonists as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations. [49592] Ibuprofen lysine: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment. [32402] Ibuprofen: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Ibuprofen; Oxycodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [60634] (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Ibuprofen; Pseudoephedrine: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Icosapent ethyl: (Moderate) Thiazide diuretics may exacerbate hypertriglyceridemia and should be discontinued or changed to alternate therapy, if possible, prior to initiation of icosapent ethyl. [51323] Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with losartan, a CYP3A substrate, as losartan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. [5339] [57675] Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known. [36146] Iloprost: (Moderate) Angiotensin II receptor antagonists can enhance the hypotensive effects of antihypertensive agents if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. [7537] Imatinib: (Minor) Imatinib, STI-571 is a potent inhibitor of the hepatic CYP2C9 isoenzyme and may inhibit the conversion of losartan to its more active metabolite E-3174. Monitor patients response to therapy closely if imatinib is added or discontinued in a patient receiving losartan. [4966] Inamrinone: (Moderate) Hypokalemia may occur due to excessive diuresis during inamrinone therapy. Fluid and electrolyte changes and renal function should be carefully monitored during inamrinone therapy. [29483] Incretin Mimetics: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control. [33489] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Indacaterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Indacaterol; Glycopyrrolate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Indapamide: (Moderate) The effects of indapamide may be additive when administered with other antihypertensive agents or diuretics. In some patients, this may be desirable, but orthostatic hypotension may occur. Angiotensin II receptor antagonists tend to reverse the potassium loss, but not the serum uric acid rise associated with thiazide diuretic monotherapy. [7737] Indomethacin: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Inotersen: (Moderate) Use caution with concomitant use of inotersen and diuretics due to the risk of glomerulonephritis and nephrotoxicity. [63624] Insulin Degludec; Liraglutide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Insulin Glargine; Lixisenatide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Insulins: (Moderate) Monitor patients receiving angiotensin II receptor antagonists concomitantly with insulin for changes in glycemic control. Angiotensin II receptor antagonists may enhance the hypoglycemic effects of insulin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. [33489] [42591] [60172] (Moderate) Monitor patients receiving insulin closely for changes in diabetic control when thiazide diuretics are instituted or discontinued; dosage adjustments may be required. Thiazide diuretics can decrease the hypoglycemic effects of insulin by producing an increase in blood glucose levels. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. [29403] [30489] Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. [30536] [30537] [30538] [30539] [30540] Ipratropium; Albuterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with losartan may result in increased serum concentrations of losartan. Losartan is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. [28608] [59042] Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when isocarboxazid is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of isocarboxazid with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of isocarboxazid and an angiotensin II receptor antagonist. [27957] [29656] (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. [27957] [29656] Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. [28325] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin significantly induces the metabolism of losartan and its more potent metabolite, E-3174, resulting in a decrease in the AUC and half-life of both compounds; monitor for potential loss of losartan activity. [28608] [62183] Isoniazid, INH; Rifampin: (Moderate) Rifampin significantly induces the metabolism of losartan and its more potent metabolite, E-3174, resulting in a decrease in the AUC and half-life of both compounds; monitor for potential loss of losartan activity. [28608] [62183] Isoproterenol: (Moderate) The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents. [28004] Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29206] [29386] (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29386] [29551] Isosorbide Mononitrate: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29206] [29386] (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29386] [29551] Ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as losartan. Ivacaftor is an inhibitor of CYP3A and a weak inhibitor of CYP2C9; losartan is metabolized by CYP3A and CYP2C9. Co-administration of ivacaftor with CYP3A and CYP2C9 substrates,such as losartan, can theoretically increase losartan exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined. [28608] [48524] Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. [28325] Ketoprofen: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Ketorolac: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Lansoprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [43594] Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [43594] Lansoprazole; Naproxen: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [43594] Lesinurad; Allopurinol: (Moderate) The occurrence of certain hypersensitivity reactions may be increased in patients with renal impairment who receive allopurinol and thiazide diuretics in combination. The precise mechanism for such events is unclear but likely immune-mediated and may be related to an effect of oxypurinol; elevated oxypurinol concentrations appear to be associated with hypersensitivity reactions; decreased clearance of this metabolite may occur with renal impairment and with the concurrent use of thiazide diuretics. Severe skin reactions include exfoliative dermatitis, toxic epidermal necrolysis and Steven's Johnson syndrome; some reactions have been fatal. In addition, thiazide diuretics, like hydrochlorothiazide, can cause hyperuricemia. Since thiazides reduce the clearance of uric acid, patients with gout or hyperuricemia may have exacerbations of their disease. [28048] [33874] [40304] Levalbuterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. [28521] (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. [5251] Levomethadyl: (Moderate) Caution is advised when using levomethadyl in combination with other agents that may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia. Agents that require monitoring for potential hypokalemia include thiazide diuretics. [3085] Levomilnacipran: (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia. [11625] [28275] [29934] [34940] [55469] Levorphanol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with levorphanol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [60958] Lidocaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Linagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Linagliptin; Metformin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Liraglutide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Lisdexamfetamine: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. [33263] (Minor) Lisdexamfetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. [33263] Lisinopril: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Lithium: (Major) Concurrent use of lithium and thiazide diuretics may result in lithium toxicity. Therapeutic doses of thiazide diuretics can result in an approximate 25% to 40% decrease in lithium clearance, potentially leading to significant toxicity. Lithium is primarily re-absorbed from the proximal tubules, and thiazide diuretics block sodium reabsorption at the distal tubule, which results in sodium depletion and subsequent compensatory reabsorption of sodium and lithium at the proximal tubules. If treatment with lithium and a thiazide diuretic cannot be avoided, patients should have their serum lithium concentrations closely monitored, and the lithium dosage adjusted if necessary. Monitoring for changes in lithium effectiveness as well as careful assessment of lithium concentrations is advisable, particularly during initial co-administration and after dose changes or discontinuation of the diuretic. In some cases, thiazide diuretics may be used to counteract lithium-induced polyuria, although close monitoring is necessary if such treatment is initiated. There is a lack of evidence to evaluate the safety of lithium and metolazone, a thiazide-like diuretic. The manufacturer of metolazone recommends general avoidance of diuretics and lithium due to the potential for lithium toxicity. [24610] [28654] [47399] [61085] (Moderate) Angiotensin II receptor antagonists (Angiotensin Receptor Blockers, or ARBs) should be used very cautiously, if at all, in patients already receiving lithium. The risk of lithium toxicity may be increased in patients receiving ARBs. ARBs decrease lithium clearance, possibly as a result of sodium depletion which leads to increased renal tubular reabsorption of lithium. Start with lower doses of lithium or reduce dosage, while frequently monitoring serum lithium concentrations and for signs/symptoms of lithium toxicity. [27991] [28654] [47399] Lixisenatide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Loop diuretics: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. [28429] [48546] (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated. [5159] [6135] Lopinavir; Ritonavir: (Moderate) Concurrent administration of losartan with ritonavir may result in elevated losartan plasma concentrations. Losartan is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together. [47165] [5339] [58664] Loratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Lovastatin; Niacin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. [44027] Lumacaftor; Ivacaftor: (Moderate) Concomitant use of losartan and lumacaftor; ivacaftor may alter the therapeutic effects of losartan; caution and close monitoring of blood pressure are advised if these drugs are used together. Losartan is primarily metabolized by CYP2C9 and is also a substrate of CYP3A4. Lumacaftor is a strong CYP3A inducer; in vitro data suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C9. Although induction of losartan through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on CYP2C9-mediated metabolism is not clear. Monitor the patient for decreased losartan efficacy or increased or prolonged therapeutic effects and adverse events. [28608] [59891] Lumacaftor; Ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as losartan. Ivacaftor is an inhibitor of CYP3A and a weak inhibitor of CYP2C9; losartan is metabolized by CYP3A and CYP2C9. Co-administration of ivacaftor with CYP3A and CYP2C9 substrates,such as losartan, can theoretically increase losartan exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined. [28608] [48524] Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known. [42227] Magnesium Salts: (Moderate) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of thiazide diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia. In addition, use caution when prescribing sulfate salt bowel preps in patients taking medications that may affect renal function such as diuretics. [30361] [41573] Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists. [41573] (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics. [41573] Mannitol: (Major) Avoid use of other diuretics with mannitol, if possible. Concomitant administration may potentiate the renal toxicity of mannitol. [33007] Meclofenamate Sodium: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Mefenamic Acid: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Meglitinides: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. [33489] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [28550] [29179] [29403] [30489] Meloxicam: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Memantine: (Minor) Memantine reduced the bioavailability of hydrochlorothiazide by roughly 20% in a drug interaction study. The clinical significance of this pharmacokinetic interaction, if any, is unknown. [5905] [8204] Mepenzolate: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Meperidine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with meperidine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [51182] Meperidine; Promethazine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with meperidine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [51182] Mequinol; Tretinoin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. [28570] Mestranol; Norethindrone: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients; monitor patients receiving concurrent therapy to confirm that the desired antihypertensive effect is being obtained. [805] Metaproterenol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Metformin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] Metformin; Repaglinide: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. [33489] [42591] (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [28550] [29179] [29403] [30489] Metformin; Rosiglitazone: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Metformin; Saxagliptin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Metformin; Sitagliptin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Methadone: (Moderate) Diuretics can cause electrolyte disturbances such as hypomagnesemia and hypokalemia, which may prolong the QT interval. As methadone may also prolong the QT interval, cautious coadministration with diuretics is needed. In addition, opiate agonists may potentiate orthostatic hypotension when used concurrently with diuretics. [29179] [33136] Methamphetamine: (Minor) Amphetamines may counteract the activity of some antihypertensive agents, such as thiazide diuretics. Close monitoring of blood pressure is advised. Thiazide diuretics may also increase and prolong the actions of amphetamines by increasing the urinary pH. [33363] (Minor) Methamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as angiotensin II receptor antagonists. Close monitoring of blood pressure is advised. [33363] Methazolamide: (Moderate) Thiazide diuretics may increase the risk of hypokalemia if used concurrently with methazolamide. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. There may also be an additive diuretic or hyperuricemic effect. [26417] [28294] Methenamine: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. [40708] Methenamine; Sodium Acid Phosphate: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. [40708] Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. [40708] (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Methenamine; Sodium Salicylate: (Moderate) Thiazide diuretics may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde. [40708] Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension. [28277] Methotrexate: (Moderate) Coadministration of thiazide diuretics and antineoplastic agents such as methotrexate may result in reduced renal excretion of the antineoplastic agent and therefore increased myelosuppressive effects. [33738] Methoxsalen: (Moderate) Concomitant administration of methoxsalen and other photosensitizing agents, such as thiazide diuretics, can increase the incidence or severity of photsensitization from either compound. [7478] Methscopolamine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Methylphenidate Derivatives: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as thiazide diuretics. [28518] [66501] (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents such as angiotensin II receptor antagonists. [28518] [66501] Metoclopramide: (Minor) Coadministration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic. [33738] Midodrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] Miglitol: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. [33489] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Milnacipran: (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia. [11625] [28275] [29934] [34940] [55469] Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response. [30865] Mirtazapine: (Moderate) Hyponatremia has been reported very rarely during mirtazapine administration. Caution is advisable in patients receiving medications known to cause hyponatremia, such as diuretics. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of mirtazapine, as well as implementation of the appropriate medical interventions. [40942] Mitotane: (Major) Use caution if mitotane and losartan are used concomitantly, and monitor for decreased efficacy of losartan and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and losartan is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of losartan. Another strong CYP3A inducer, rifampin, decreased the AUC and half-life of losartan by 35% and 50%, respectively. In addition, rifampin decreased the AUC and half-life for the active metabolite of losartan, E-3174, by 40% and 50%, respectively. [28608] [41934] Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane. [52452] [52503] [65487] Moexipril: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Morphine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with morphine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. Morphine may also cause acute urinary retention by causing a spasm of the bladder sphincter; men with enlarged prostates may have a higher risk of this reaction. [29179] [40951] Morphine; Naltrexone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a thiazide diuretic is administered with morphine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. Morphine may also cause acute urinary retention by causing a spasm of the bladder sphincter; men with enlarged prostates may have a higher risk of this reaction. [29179] [40951] Nabumetone: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Naproxen: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Naproxen; Esomeprazole: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] (Moderate) Proton pump inhibitors, such as esomeprazole, have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [29524] [43594] Naproxen; Pseudoephedrine: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Nateglinide: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. [33489] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [28550] [29179] [29403] [30489] Nefazodone: (Minor) Although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring and dosage adjustments of either drug may be necessary. [5414] (Minor) Although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring is recommended. Dependent upon clinical response, dosage adjustments of either drug may be necessary. [5414] Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents. [29061] (Moderate) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents. [29061] Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane. [52452] [52503] [65487] Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. [44027] Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. [44027] Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of losartan with ritonavir may result in elevated losartan plasma concentrations. Losartan is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together. [47165] [5339] [58664] Nitrates: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29206] [29386] (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29386] [29551] Nitroglycerin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29206] [29386] (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary. [29386] [29551] Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure. [29571] (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure. [49213] Non-Ionic Contrast Media: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure. [28963] [49612] Nonsteroidal antiinflammatory drugs: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] (Moderate) Nonsteroidal antiinflammatory drugs (NSAIDs) (including selective COX-2 inhibitors) may alter the response to Angiotensin II receptor blockers due to inhibition of vasodilatory prostaglandins. Among NSAIDs, indomethacin, naproxen, and piroxicam may have the greatest pressor effect, while the effects of sulindac and nabumetone may be significantly less. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function who are being treated with NSAIDs, coadministration of angiotensin II receptor antagonists may result in further deterioration of renal function, including acute renal failure. These effects are usually reversible. [24233] [27388] [27991] [28608] [29130] [60860] Norepinephrine: (Moderate) Thiazide diuretics can cause decreased arterial responsiveness to norepinephrine, but the effect is not sufficient to preclude their coadministration. [29179] Octreotide: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects. [29113] Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents. [5517] Olanzapine; Fluoxetine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents. [5517] (Moderate) Patients receiving a diuretic during treatment with fluoxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluoxetine should be considered in patients who develop symptomatic hyponatremia. [32127] (Minor) Inhibitors of the hepatic CYP2C9 isoenzyme, such as fluoxetine, have potential to inhibit the conversion of losartan to its active metabolite. Monitor therapeutic response to individualize losartan dosage. [4192] Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents. [5517] Oliceridine: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [65809] Olodaterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of losartan with ritonavir may result in elevated losartan plasma concentrations. Losartan is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together. [47165] [5339] [58664] Omeprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [43594] Omeprazole; Amoxicillin; Rifabutin: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [43594] Omeprazole; Sodium Bicarbonate: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [43594] Ondansetron: (Moderate) The coadministration of ondansetron with diuretics associated with hypokalemia could increase the risk of QT prolongation. Potassium levels should be within the normal range prior to and during therapy with ondansetron. [31266] Oprelvekin, rh-IL-11: (Major) Patients receiving thiazide diuretics during oprelvekin, rh-IL-11 therapy are at increased risk for developing severe hypokalemia; close monitoring of fluid and electrolyte status is warranted during concurrent diuretic and oprelvekin therapy. [26656] [3330] Oxaprozin: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Oxybutynin: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Oxycodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [60634] Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. If these drugs are used together, closely monitor for changes in blood pressure. [26181] [61733] (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by diuretics. If these drugs are used together, closely monitor for changes in blood pressure. [26181] [61733] Oxymorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with oxymorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [32438] Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and angiotensin II receptor antagonists who are susceptible to hypotension. [32936] [40936] (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and thiazide diuretics who are susceptible to hypotension. [32936] [40936] Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane. [52452] [52503] [65487] Pantoprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [43594] Paroxetine: (Moderate) Patients receiving a diuretic during treatment with paroxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of paroxetine should be considered in patients who develop symptomatic hyponatremia. [28260] Pasireotide: (Moderate) Cautious use of pasireotide and thiazide diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt. [52611] Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and losartan, a CYP3A4 substrate, may cause an increase in systemic concentrations of losartan. Use caution when administering these drugs concomitantly. [28608] [37098] Pentamidine: (Moderate) Drugs that are associated with hypokalemia and/or hypomagnesemia such as thiazide diuretics should be used with caution in patients also receiving pentamidine. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss. Closely monitor serum electrolytes during pentamidine therapy. [24022] [26417] [28879] Pentazocine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [30219] Pentazocine; Naloxone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [30219] Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced. [6316] Perindopril: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Perindopril; Amlodipine: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Phendimetrazine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] Phenelzine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. [27957] [29656] (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists. [27957] [29656] Phenobarbital: (Moderate) Phenobarbital causes a reduction of approximately 20 percent in the AUC of losartan and its metabolite. The clinical significance of this interaction is unknown. [28608] Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Phenobarbital causes a reduction of approximately 20 percent in the AUC of losartan and its metabolite. The clinical significance of this interaction is unknown. [28608] (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Phenothiazines: (Moderate) Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, and electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes), particularly with mesoridazine, thioridazine, or chlorpromazine. In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics. [26417] [28997] [29179] [30713] Phentermine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Phentermine; Topiramate: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Phenytoin: (Minor) Phenytoin may inhibit the CYP2C9-mediated conversion of losartan to its active metabolite. A reduced clinical effect of losartan is possible via reduced formation of a metabolite which significantly contributes to the efficacy of losartan. [4060] Photosensitizing agents (topical): (Moderate) Thiazide diuretics may cause photosensitivity and may increase the photosensitization effects of photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin. [29179] [30713] Pimozide: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment. [43463] Pioglitazone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Pioglitazone; Glimepiride: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Pioglitazone; Metformin: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of metformin by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. ARBs may rarely reduce renal function, a risk factor for reduced renal clearance of metformin. Patients receiving these drugs together should be monitored for changes in renal function and glycemic control. [28550] [33489] [42591] (Moderate) Certain drugs, such as thiazide diuretics, tend to produce hyperglycemia and may lead to loss of glycemic control. The effects of thiazide diuretics on glycemic control appear to be dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, thiazide diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. Patients receiving metformin should be monitored for changes in blood glucose control if any of these diuretics are added or deleted. Dosage adjustments may be necessary in some patients. [29403] [30489] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Pirbuterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Piroxicam: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Polycarbophil: (Moderate) Coadministration may lead to hypercalcemia because thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium polycarbophil is used concomitantly, monitoring of serum calcium may be prudent. [29179] Polyethylene Glycol; Electrolytes: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists. [41573] (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics. [41573] Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists. [41573] (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics. [41573] Porfimer: (Major) Avoid coadministration of porfimer with thiazide diuretics due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like thiazide diuretics may increase the risk of a photosensitivity reaction. [42968] Potassium Phosphate: (Major) Avoid coadministration of potassium phosphate and angiotensin II receptor antagonists as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations. [49592] Potassium Phosphate; Sodium Phosphate: (Major) Avoid coadministration of potassium phosphate and angiotensin II receptor antagonists as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations. [49592] Potassium: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and angiotensin II receptor antagonists are used together. Concomitant use may increase the risk of hyperkalemia. [28608] [29130] [30272] [57713] Pramlintide: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of pramlintide by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with pramlintide should be monitored for changes in glycemic control. [33489] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used. [29327] (Moderate) razosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used. [6065] Prilocaine; Epinephrine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Probenecid: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid. [29397] Probenecid; Colchicine: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid. [29397] Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects. [28250] (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects. [4977] Procaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. [28996] [29080] (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. [5731] [5815] Promethazine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Well-controlled hypertensive patients receiving phenylephrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients. [24172] [26181] [27369] (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients. [2843] [4065] [741] Propantheline: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. [28325] Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Pseudoephedrine; Triprolidine: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [6234] (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by angiotensin II receptor antagonists. Monitor heart rate and blood pressure. [26181] [29548] Quetiapine: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine. [29118] Quinapril: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension. [28249] Rabeprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. [40337] [43594] Ramipril: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Rapacuronium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane. [52452] [52503] [65487] Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. [27957] [29656] (Moderate) Additive hypotensive effects may be seen when rasagiline is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during coadministration. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. [27957] [29656] Remifentanil: (Moderate) Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. [29179] Repaglinide: (Moderate) Angiotensin II receptor antagonists (ARB) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. [33489] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [28550] [29179] [29403] [30489] Rifampin: (Moderate) Rifampin significantly induces the metabolism of losartan and its more potent metabolite, E-3174, resulting in a decrease in the AUC and half-life of both compounds; monitor for potential loss of losartan activity. [28608] [62183] Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of angiotensin II receptor antagonists. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving angiotensin II receptor antagonists concomitantly. [28414] (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly. [28414] Ritonavir: (Moderate) Concurrent administration of losartan with ritonavir may result in elevated losartan plasma concentrations. Losartan is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together. [47165] [5339] [58664] Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane. [52452] [52503] [65487] Rofecoxib: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Rosiglitazone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Salicylates: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Salmeterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Saxagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Scopolamine: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Semaglutide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Serotonin norepinephrine reuptake inhibitors: (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia. [11625] [28275] [29934] [34940] [55469] Sertraline: (Moderate) Patients receiving a diuretic during treatment with sertraline may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of sertraline should be considered in patients who develop symptomatic hyponatremia. [28343] Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. [28325] SGLT2 Inhibitors: (Moderate) Patients receiving these drugs concomitantly should be monitored for changes in blood pressure, volume status, renal function, serum potassium and other electrolytes, and for glycemic control. When an SGLT2 inhibitor is initiated, mild diuresis and naturesis occurs, producing intravascular volume contraction. These effects may be additive to certain antihypertensive medications, such as the angiotensin II receptor antagonists (also known as angiotensin receptor blockers or ARBs). Patients with impaired renal function (eGFR less than 60 mL/minute/1.73 m2), low systolic blood pressure, or who are elderly may also be at a greater risk. Volume status should be assessed and corrected. In addition, some SGLT2 inhibitors, like canagliflozin, can increase serum potassium. Monitor serum potassium levels periodically and monitor for hyperkalemia. ARBs may also enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. [29403] [30585] [33489] [42591] [53972] [56603] [57718] [62718] Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. [11340] (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. [34483] Simvastatin; Sitagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Sitagliptin: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29179] [29403] [30489] Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as angiotensin II receptor antagonists, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. [32159] [32160] (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics, may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. [32159] [32160] Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as angiotensin II receptor antagonists. In addition, use caution in patients receiving drugs where hypokalemia is a particular risk. [51258] (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as diuretics. In addition, use caution in patients receiving drugs where hypokalemia is a particular risk. [51258] Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of thiazide diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia. In addition, use caution when prescribing sulfate salt bowel preps in patients taking medications that may affect renal function such as diuretics. [30361] [41573] Solifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. Risk versus benefit should be addressed in patients receiving diuretics and solifenacin. [30361] Spironolactone: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients. [28608] [29016] [29134] [60860] Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium concentrations closely if angiotensin II receptor antagonists and spironolactone are used together. Concomitant use may increase the risk of hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients. [28608] [29016] [29134] [60860] St. John's Wort, Hypericum perforatum: (Moderate) St. John's Wort appears to induce several isoenzymes of the hepatic cytochrome P450 enzyme system and could decrease the efficacy of some medications metabolized by these enzymes including losarten. [4935] Streptozocin: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g,. aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult. [6757] Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane. [52452] [52503] [65487] Sufentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [29179] [30966] Sulfacetamide: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of thiazide diuretics. [7114] [7476] Sulfacetamide; Sulfur: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of thiazide diuretics. [7114] [7476] Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. [43890] (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors. [43890] [55864] [67024] [67025] Sulfinpyrazone: (Moderate) Sulfinpyrazone facilitates urinary excretion of uric acid and thereby decreases plasma urate concentrations. Thiazide diuretics can cause hyperuricemia. Dosage adjustments of sulfinpyrazone may be necessary if thiazides are administered concurrently. [31054] Sulfonamides: (Minor) Inhibitors of the hepatic CYP2C9 isoenzyme, such as sulfonamides, have potential to inhibit the conversion of losartan to its active metabolite. Monitor therapeutic response to individualize losartan dosage. [4192] Sulfonylureas: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. [33489] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Sulindac: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Sumatriptan; Naproxen: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Tapentadol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with tapentadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [36077] Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. [28587] [28588] Tegaserod: (Minor) Coadminisitration of thiazides and prokinetic agents may result in decreased bioavailability of the thiazide diuretic. [33738] Terbutaline: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly. [34389] Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents. [28996] [29080] Tezacaftor; Ivacaftor: (Moderate) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as losartan. Ivacaftor is an inhibitor of CYP3A and a weak inhibitor of CYP2C9; losartan is metabolized by CYP3A and CYP2C9. Co-administration of ivacaftor with CYP3A and CYP2C9 substrates,such as losartan, can theoretically increase losartan exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined. [28608] [48524] Thiazolidinediones: (Moderate) Angiotensin II receptor antagonists (ARBs) may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving an ARB in combination with antidiabetic agents should be monitored for changes in glycemic control. [33489] [42591] (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Thiopental: (Moderate) Concurrent use of thiopental and alpha-blockers or antihypertensive agents increases the risk of developing hypotension. [30143] Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible. [5732] [5750] [5888] [7932] [7933] [7934] Tiotropium; Olodaterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Tirzepatide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. [29403] Tizanidine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy. [30150] Tolazamide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Tolbutamide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. [29179] [29403] [30489] Tolmetin: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Tolterodine: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. [30361] Tolvaptan: (Moderate) Monitor serum potassium concentrations closely if tolvaptan and angiotensin II receptor blockers are used together. In clinical studies, hyperkalemia was reported at a rate 1% to 2% higher when tolvaptan was administered with angiotensin II receptor blockers compared to administration of these medications with placebo. [35780] (Moderate) Monitor serum sodium closely if tolvaptan and thiazide diuretics are used together. Coadministration increases the risk of too rapid correction of serum sodium. [35780] Topiramate: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] Toremifene: (Moderate) Monitor serum calcium levels in patients receiving concomitant treatment with toremifene and thiazide diuretics. Thiazide diuretics decrease renal calcium excretion and may increase the risk of hypercalcemia in patients receiving toremifene. [28822] Tramadol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with tramadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [28314] Tramadol; Acetaminophen: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when thiazide diuretics are administered with tramadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. [28314] Trandolapril: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Trandolapril; Verapamil: (Moderate) Patients with hyponatremia or hypovolemia are more susceptible to developing reversible renal insufficiency when given angiotensin converting enzyme (ACE) inhibitors and diuretics concomitantly. [29147] [29179] Tranylcypromine: (Contraindicated) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated. [29656] Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone. [28719] Treprostinil: (Moderate) Thiazide diuretics can enhance the hypotensive effects of antihypertensive agents or diuretics if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. [5917] [6960] Tretinoin, ATRA: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. [28570] Tretinoin; Benzoyl Peroxide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas. [28570] Triamterene: (Major) Potassium-sparing diuretics, such as triamterene, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients. [28608] [29160] [43532] [60860] Triamterene; Hydrochlorothiazide, HCTZ: (Major) Potassium-sparing diuretics, such as triamterene, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients. [28608] [29160] [43532] [60860] Trihexyphenidyl: (Minor) Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms. [29247] [33738] Trimethoprim: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. Avoid concomitant use and consider alternative antibiotic therapy in patients with additional risk factors for hyperkalemia, including patients older than 65 years, those with underlying disorders of potassium metabolism, renal insufficiency, or those requiring high doses of trimethoprim. Amongst patients older than 65 years, concomitant use has been associated with a 2- to 7-fold increased risk of significant hyperkalemia compared to other antibiotics. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors. [43890] [55864] [67024] [67025] Trospium: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. [5985] Tubocurarine: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane. [52452] [52503] [65487] Umeclidinium; Vilanterol: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Valdecoxib: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and thiazide diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane. [52452] [52503] [65487] Vemurafenib: (Moderate) Concomitant use of vemurafenib and losartan may result in altered concentrations of losartan. Vemurafenib is an inhibitor of CYP2C9 and an inducer of CYP3A4. Losartan is a substrate of CYP2C9 and CYP3A4. Use caution and monitor patients for toxicity and efficacy. [45335] [5339] Venlafaxine: (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia. [11625] [28275] [29934] [34940] [55469] Verteporfin: (Moderate) Use caution if coadministration of verteporfin with thiazide diuretics is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like thiazide diuretics may increase the risk of a photosensitivity reaction. [30003] Vigabatrin: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as losartan, may occur during concurrent use of vigabatrin. [36250] Vilazodone: (Moderate) Patients receiving vilazodone with medications known to cause hyponatremia, such as diuretics, may be at increased risk of developing hyponatremia. Hyponatremia has occurred in association with the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of vilazodone, as well as implementation of the appropriate medical interventions. [40942] [43177] Vitamin D analogs: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. [27970] [30166] [34775] [60895] Vitamin D: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. [27970] [30166] [34775] [60895] Vitamin D: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. [27970] [30166] [34775] [60895] Voriconazole: (Minor) Coadministration of losartan with voriconazole may result in increased exposure to losartan but decreased concentrations of the active metabolite. The conversion of losartan to its active metabolite is primarily mediated by CYP2C9; voriconazole is an inhibitor of CYP2C9. When coadministered with another inhibitor of CYP2C9, the AUC of the active metabolite of losartan was decreased by 40%, but the AUC of losartan increased by 70%. [27491] [28608] Vorinostat: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary. [26417] [32789] Vortioxetine: (Moderate) Patients receiving a diuretic during treatment with vortioxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Clinically significant hyponatremia has been reported during therapy with vortioxetine. One case involving serum sodium levels lower than 110 mmol/l has occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of vortioxetine should be considered in patients who develop symptomatic hyponatremia. [56041] Yohimbine: (Moderate) Yohimbine can increase blood pressure and therefore can antagonize the therapeutic action of antihypertensive agents. Use with particular caution in hypertensive patients with high or uncontrolled blood pressure. [28863] [29542] Zafirlukast: (Minor) Zafirlukast inhibits the CYP2C9 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP2C9, such as losartan. [4718] [4948] Ziconotide: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation. [30603] Ziprasidone: (Moderate) Monitor potassium and magnesium levels when thiazide diuretics are used during ziprasidone therapy. The risk of QT prolongation from ziprasidone is increased in the presence of hypokalemia or hypomagnesemia. [28233] (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents. [28233]
      Revision Date: 05/20/2022, 02:28:00 AM

      References

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      Monitoring Parameters

      • blood glucose
      • blood pressure
      • LFTs
      • serum bilirubin (total and direct)
      • serum creatinine/BUN
      • serum electrolytes
      • serum uric acid

      US Drug Names

      • Hyzaar
      ;