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TRANSFORMAR COMO VOCÊ USA INFORMAÇÕES SOBRE DROGAS

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Mar.29.2022

Hydroxychloroquine

Indications/Dosage

Labeled

  • discoid lupus erythematosus
  • malaria
  • malaria prophylaxis
  • rheumatoid arthritis
  • systemic lupus erythematosus (SLE)

Off-Label

  • lupus nephritis
  • polymorphous light eruption
  • coronavirus disease 2019 (COVID-19)
  • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
† Off-label indication

INVESTIGATIONAL USE: For the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection†, the virus that causes coronavirus disease 2019 (COVID-19)†

Oral dosage

Adults weighing 50 kg or more

Available data are limited and inconclusive. The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of hydroxychloroquine for the treatment of COVID-19 patients.[65314] The FDA has revoked the Emergency Use Authorization (EUA) of hydroxychloroquine.[65586] Previously, the EUA suggested 800 mg (620 mg base) PO on day 1 then 400 mg (310 mg base) PO daily for 4 to 7 days.[65171] [65173] Other dosing regimens, alone and in combination, are being evaluated.[65844]

Adolescents weighing 50 kg or more

Available data are limited and inconclusive. The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of hydroxychloroquine for the treatment of COVID-19 patients.[65314] The FDA has revoked the Emergency Use Authorization (EUA) of hydroxychloroquine.[65586] Previously, the EUA suggested 800 mg (620 mg base) PO on day 1 then 400 mg (310 mg base) PO daily for 4 to 7 days.[65171] [65173]

For the treatment of uncomplicated malaria due to susceptible strains of P. falciparum, P. knowlesi†, P. malariae, P. ovale, and P. vivax

Oral dosage

Adults

800 mg (620 mg base) PO, then 400 mg (310 mg base)/dose PO at 6, 24, and 48 hours after the initial dose for a total dose of 2,000 mg (1,550 mg base). For P. vivax or P. ovale, give in combination with primaquine phosphate or tafenoquine. Guidelines recommend hydroxychloroquine for uncomplicated malaria in patients with chloroquine-sensitive P. falciparum or P. vivax or in all patients with P. malariae, P. knowlesi, or P. ovale.[41806] [64059]

Children and Adolescents weighing 31 kg or more

13 mg (10 mg base)/kg/dose [Max: 800 mg (620 mg base)/dose] PO, then 6.5 mg (5 mg base)/kg/dose [Max: 400 mg (310 mg base)/dose] PO at 6, 24, and 48 hours after the initial dose for a total dose of 32.5 mg (25 mg base)/kg [Max: 2,000 mg (1,550 mg base)]. For P. vivax or P. ovale, give in combination with primaquine phosphate or tafenoquine (16 years and older). Guidelines recommend hydroxychloroquine for uncomplicated malaria in patients with chloroquine-sensitive P. falciparum or P. vivax or in all patients with P. malariae, P. knowlesi, or P. ovale.[41806] [64059]

Infants, Children, and Adolescents weighing less than 31 kg†

13 mg (10 mg base)/kg/dose [Max: 800 mg (620 mg base)/dose] PO, then 6.5 mg (5 mg base)/kg/dose [Max: 400 mg (310 mg base)/dose] PO at 6, 24, and 48 hours after the initial dose for a total dose of 32.5 mg (25 mg base)/kg [Max: 2,000 mg (1,550 mg base)]. For P. vivax or P. ovale, give in combination with primaquine phosphate or tafenoquine (16 years and older). Guidelines recommend hydroxychloroquine for uncomplicated malaria in patients with chloroquine-sensitive P. falciparum or P. vivax or in all patients with P. malariae, P. knowlesi, or P. ovale.[41806] [64059]

For malaria prophylaxis in areas where chloroquine-resistance has not been reported

Oral dosage

Adults

400 mg (310 mg base)/dose PO weekly on the same day of each week, starting 1 to 2 weeks before entering the endemic area and continuing for 4 weeks after leaving the area. Guidelines suggest hydroxychloroquine as an alternative to chloroquine.[41806] [63990]

Children and Adolescents weighing 31 kg or more

6.5 mg (5 mg base)/kg/dose [Max: 400 mg (310 mg base)/dose] PO weekly on the same day of each week, starting 1 to 2 weeks before entering the endemic area and continuing for 4 weeks after leaving the area. Guidelines suggest hydroxychloroquine as an alternative to chloroquine.[41806] [63990] [66745]

Infants, Children, and Adolescents weighing less than 31 kg†

6.5 mg (5 mg base)/kg/dose [Max: 400 mg (310 mg base)/dose] PO weekly on the same day of each week, starting 1 to 2 weeks before entering the endemic area and continuing for 4 weeks after leaving the area. Guidelines suggest hydroxychloroquine as an alternative to chloroquine.[63990] [66745]

For the treatment of rheumatoid arthritis

for the initial treatment of rheumatoid arthritis

Oral dosage

Adults

400 to 600 mg (310 to 465 mg base) PO once daily or in 2 divided doses as monotherapy or part of combination therapy. Side effects may require a temporary initial dose reduction. After a clinical response is obtained, reduce the chronic dose.[41806] [65215]

for the chronic maintenance treatment of rheumatoid arthritis

Oral dosage

Adults

200 mg (155 mg base) PO once daily or 400 mg (310 mg base) PO once daily or in 2 divided doses.[41806] [65215]

For the treatment of systemic lupus erythematosus (SLE)

Oral dosage

Adults

200 mg (155 mg base) PO once daily or 400 mg (310 mg base) PO once daily or in 2 divided doses.[41806]

Children† and Adolescents†

4 to 6 mg (3.1 to 4.6 mg base)/kg/day PO.[64633] [65218] [65219] [65220]

For the treatment of discoid lupus erythematosus

Oral dosage

Adults

200 mg (155 mg base) PO once daily or 400 mg (310 mg base) PO once daily or in 2 divided doses.[41806] May add quinacrine if a patient fails monotherapy.[62154] [65216]

For the treatment of lupus nephritis†

Oral dosage

Adults

200 to 400 mg/day (155 to 310 mg/day base) PO. Max: 5 mg/kg/day.[52522] [65217]

For the suppression of polymorphous light eruption†

Oral dosage

Adults

200 to 400 mg (155 to 310 mg base) PO once daily or in 2 divided doses.[61732]

Therapeutic Drug Monitoring

The following recommendations are for baseline and continuous monitoring when using hydroxychloroquine with azithromycin:

  • Obtain a pre-treatment QTc using a standard 12-lead ECG, telemetry, or mobile ECG device.
  • Obtain baseline electrolytes, including calcium, magnesium, and potassium; correct abnormalities.
  • Determine if the patient is currently on any QT-prolonging medications that can be discontinued.[65170]
  • Document high-risk cardiovascular and comorbid conditions.[65170] Assess and adjust for hepatic and renal dysfunction.[65242]

 

Inpatient Use

  • Place telemetry prior to initiation, if possible.
  • Monitor and optimize serum electrolytes daily.[65242]
  • If the baseline QTc is 500 msec or more and/or the patient has an inherent tendency to develop an exaggerated QTc response (i.e., change of 60 msec or more), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and proceed with close QTc surveillance.[65170] Some experts recommend withholding treatment for patients with a baseline QTc of 500 msec or more (or more than 530 to 550 msec in patients with a QRS interval more than 120 msec) or in those with congenital long QT syndrome.[65242]
  • If the baseline QTc is 460 to 499 msec (prepubertal), 470 to 499 msec (postpubertal males), or 480 to 499 msec (postpubertal females), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and obtain an initial on-therapy QTc daily (or 48 and 96 hours after treatment initiation).[65170] [65242]
  • If the baseline QTc is less than 460 msec (prepubertal), less than 470 msec (postpubertal males), or less than 480 msec (postpubertal females), correct electrolyte abnormalities and obtain an initial on-therapy QTc daily (or 48 and 96 hours after treatment initiation).[65170] [65242]
  • Obtain an initial on-therapy QTc approximately 2 to 4 hours after the first dose and then daily (some recommend 48 and 96 hours after treatment initiation).[65170] [65242]
  • Discontinue azithromycin and/or reduce the antimalarial dose if the subsequent QTc is prolonged or significantly increased above the specified parameters. If the QTc remains prolonged or significantly increased, reevaluate the risk/benefit of therapy, consider consultation with an electrophysiologist, and consider hydroxychloroquine/chloroquine discontinuation.[65242]

 

Outpatient Use

  • Do not initiate outpatient therapy in the setting of acute renal or hepatic failure.[65242]
  • If the baseline QTc is 500 msec or more and/or the patient has an inherent tendency to develop an exaggerated QTc response (i.e., change of 60 msec or more), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and proceed with close QTc surveillance.[65170] Some experts recommend withholding treatment in patients with a baseline QTc of 480 msec or more (or more than 510 to 530 msec in patients with a QRS interval more than 120 msec), congenital long QT syndrome, or a Tisdale risk score of 11 or more.[65242]
  • Consider no further ECG/telemetry assessment for patients with a Tisdale risk score of 6 or less, if resource or quarantine constraints are prohibitive of monitoring. Otherwise, repeat the ECT 2 to 3 hours after dosing on day 3 of therapy. If the QTc exceeds 500 msec (or 530 to 550 msec if QRS is more than 120 msec) or increases by more than 30 to 60 msec, consider discontinuing therapy.[65242]

Maximum Dosage Limits

  • Adults

    800 mg/dose (620 mg base/dose) PO for malaria up to a total of 2,000 mg (1,550 mg base) PO in 48 hours; 400 mg/week (310 mg base/week) PO for malaria prophylaxis; 600 mg/day (465 mg base/day) PO for rheumatoid arthritis; 400 mg/day (310 mg base/day) PO for systemic lupus erythematosus and chronic discoid lupus erythematosus

  • Geriatric

    800 mg/dose (620 mg base/dose) PO for malaria up to a total of 2,000 mg (1,550 mg base) PO in 48 hours; 400 mg/week (310 mg base/week) PO for malaria prophylaxis; 600 mg/day (465 mg base/day) PO for rheumatoid arthritis; 400 mg/day (310 mg base/day) PO for systemic lupus erythematosus and chronic discoid lupus erythematosus

  • Adolescents

    weighing 31 kg or more: 13 mg/kg/dose (10 mg base/kg/dose) [Max: 800 mg (620 mg base)] PO for malaria up to a total of 32.5 mg/kg (25 mg base/kg) [Max: 2,000 mg (1,550 mg base)] PO in 48 hours; 6.5 mg/kg/week (5 mg base/kg/week) [Max: 400 mg/week (310 mg base/week)] PO for malaria prophylaxis.

    weighing less than 31 kg: 13 mg/kg/dose (10 mg base/kg/dose) PO for malaria up to a total of 32.5 mg/kg (25 mg base/kg) PO in 48 hours has been used off-label; 6.5 mg/kg/week (5 mg base/kg/week) PO for malaria prophylaxis has been used off-label.

  • Children

    weighing 31 kg or more: 13 mg/kg/dose (10 mg base/kg/dose) [Max: 800 mg (620 mg base)] PO for malaria up to a total of 32.5 mg/kg (25 mg base/kg) [Max: 2,000 mg (1,550 mg base)] PO in 48 hours; 6.5 mg/kg/week (5 mg base/kg/week) [Max: 400 mg/week (310 mg base/week)] PO for malaria prophylaxis.

    weighing less than 31 kg: 13 mg/kg/dose (10 mg base/kg/dose) PO for malaria up to a total of 32.5 mg/kg (25 mg base/kg) PO in 48 hours has been used off-label; 6.5 mg/kg/week (5 mg base/kg/week) PO for malaria prophylaxis has been used off-label.

  • Infants

    13 mg/kg/dose (10 mg base/kg/dose) PO for malaria up to a total of 32.5 mg/kg (25 mg base/kg) PO in 48 hours has been used off-label; 6.5 mg/kg/week (5 mg base/kg/week) PO for malaria prophylaxis has been used off-label.

  • Neonates

    Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

A dosage reduction may be necessary in patients with hepatic disease or those taking concomitant medications known to affect the liver. However, no specific dosage adjustment guidelines are available for patients with hepatic impairment.[41806]

Patients with Renal Impairment Dosing

A dosage adjustment is not required in patients with renal impairment. However, a dosage reduction may be necessary in patients with renal disease or those taking concomitant medications known to affect the kidney. No specific dosage adjustment guidelines are available for patients with renal impairment.[41806]

† Off-label indication
Revision Date: 03/29/2022, 02:20:39 PM

References

41806 - Plaquenil (hydroxychloroquine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, Inc.; 2022 May.52522 - Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care and Research 2012;64(6):797-808.61732 - Ben-Zvi H, Kivity S, Langevitz P, et al. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol 2012;42:145-53.62154 - Okon LG, Werth VP. Cutaneous lupus erythematosus: diagnosis and treatment. Best Pract Res Clin Rheumatol 2013;27:391-404.63990 - Arguin PM, Tan KR. Chapter 3. Infectious diseases related to travel. Malaria. In. Centers for Disease Control and Prevention. 2018 Yellow Book - Traveler's Health. Atlanta: U.S. Department of Health and Human Services, Public Health Service. https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/malaria64059 - Centers for Disease Control and Prevention. Treatment of malaria (guidelines for clinicians). Atlanta, GA: US Department of Health and Human Services; 2019. https://www.cdc.gov/malaria/diagnosis_treatment/treatment.html.64633 - Fanouriakis A, Kostopoulou M, Alunno A et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 2019;78:736-745.65170 - Giudicessi JR, Noseworthy PA, Friedman PA, Ackerman MJ. Urgent guidance for navigating and circumventing the QTc prolonging and torsadogenic potential of possible pharmacotherapies for COVID-19 [published online ahead of print, March 25, 2020]. Mayo Clin Proc 2020;95.65171 - Food and Drug Administration (FDA). Chloroquine phosphate or hydroxychloroquine sulfate supplied from the strategic national stockpile for treatment of 2019 coronavirus disease: emergency use authorization letter. Retrieved March 30, 2020. Available on the World Wide Web at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#2019-ncov.65173 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of hydroxychloroquine sulfate supplied from the strategic national stockpile for treatment of COVID-19 in certain hospitalized patients. Retrieved March 30, 2020. Available on the World Wide Web at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#2019-ncov.65215 - Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2016;68:1-26.65216 - Garza-Mayers AC, McClurkin M, Smith GP. Review of treatment for discoid lupus erythematosus. Dermatologic Therapy 2016;29:274-83.65217 - Fanouriakis An, Kostopoulou M, Cheema K, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA–EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis 2020.65218 - Thakral A, Klein-Gitelman MS. An update on the treatment and management of pediatric systemic lupus erythematosus. Rheumatol Ther 2016;3:209-19.65219 - Groot N, de Graeff N, Avcin T, et al. European evidence-based recommendations for diagnosis and treatment of childhood-onset systemic lupus erythematosus: the SHARE initiative. Ann Rheum Dis 2017;76:1788-96.65220 - Smith EMD, Lythgoe H, Midgley A, et al. Juvenile-onset systemic lupus erythematosus: update on clinical presentation, pathophysiology, and treatment options. Clin Immunol 2019;209:108274.65242 - Simpson TF, Kovacs RJ, Stecker EC. Ventricular arrhythmia risk due to hydroxychloroquine-azithromycin treatment for COVID-19. Accessed April 10, 2020. Available at: https://www.acc.org/latest-in-cardiology/articles/2020/03/27/14/00/ventricular-arrhythmia-risk-due-to-hydroxychloroquine-azithromycin-treatment-for-covid-1965314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed November 10, 2022. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.65586 - Food and Drug Administration (FDA). Coronavirus (COVID-19) update: FDA revokes emergency use authorization for chloroquine and hydroxychloroquine. Retrieved June 15, 2020. Available on the World Wide Web at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and65844 - ClinicalTrials.gov. National Institutes of Health (NIH) U.S. National Library of Medicine ClinicalTrials.gov website https://clinicaltrials.gov.66745 - American Academy of Pediatrics. Red Book: 2021-2024 Report of the Committee on Infectious Diseases. 32nd ed. Elk Grove Village, IL: American Academy of Pediatrics; 2021.

How Supplied

Hydroxychloroquine Sulfate Oral tablet

Hydroxychloroquine Sulfate 100mg Tablet (16729-0561) (Accord Healthcare, Inc.) null

Hydroxychloroquine Sulfate Oral tablet

Hydroxychloroquine Sulfate 200mg Tablet (16729-0485) (Accord Healthcare, Inc.) null

Hydroxychloroquine Sulfate Oral tablet

Hydroxychloroquine Sulfate 200mg Tablet (65162-0610) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)

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Description/Classification

Description

Hydroxychloroquine is an oral disease-modifying antirheumatic drug (DMARD) used to treat rheumatoid arthritis and systemic lupus erythematosus. It also is used to prevent and treat malaria. Irreversible retinal damage has been observed with use, and cases of life-threatening and fatal cardiomyopathy, including ventricular arrhythmias and torsade de pointes, have been reported.[41806] Hydroxychloroquine was FDA-approved in 1955.

 

Updates for coronavirus disease 2019 (COVID-19):

Available data are limited and inconclusive. The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of hydroxychloroquine for the treatment of COVID-19 patients. The NIH also recommends against the use of hydroxychloroquine for pre-exposure or post-exposure prophylaxis.[65314] On June 15, 2020, the FDA revoked the Emergency Use Authorization (EUA) for hydroxychloroquine stating that it is unlikely to be effective in treating COVID-19. Also, in light of ongoing serious cardiac adverse events and other serious side effects, the known and potential benefits of hydroxychloroquine no longer outweigh the known and potential risks for the authorized use.[65586] The FDA had previously issued the EUA for the use of hydroxychloroquine to treat hospitalized COVID-19 patients for whom clinical trial participation is not feasible.[65171][65173] Use in COVID-19 patients outside of clinical trials or in a nonhospital setting is not recommended due to the potential for serious adverse events and drug interactions.[65332]

 

While early reviews demonstrated potential in vitro efficacy of hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), treatment studies generally have not demonstrated improved clinical outcomes for COVID-19. These studies have mainly been observational, open-label, or retrospective in nature.

  • In a multicenter, parallel, open-label, randomized trial in 150 adult hospitalized patients, hydroxychloroquine (n = 75) was added to standard therapy. The overall 28-day negative viral conversion rate was not different and there was no difference in the 28-day symptom alleviation rate between the groups. Adverse events were reported in 9% of the control group and 30% of the hydroxychloroquine group.[65277]
  • Observational data (n = 1,376) examined the association between hydroxychloroquine use and intubation or death at a large medical center. Hydroxychloroquine was not associated with a significantly higher or lower risk of intubation or death.[65386]
  • Data from an observational study of 1,438 hospitalized patients, demonstrated no difference in mortality in patients treated with hydroxychloroquine, azithromycin, or compared with no use of these agents.[65415]
  • In a randomized, multicenter, double-blind, placebo-controlled trial (n = 423), symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probably COVID-19 and high-risk exposure received either hydroxychloroquine or masked placebo for 5 days. Change in symptom severity over 14 days did not differ between the groups based on self-assessment.[65718]
  • In a multicenter, open-label, randomized controlled trial (n = 270), nonhospitalized adult patients with recently confirmed SARS-CoV-2 infection with less than 4 days of symptoms received either hydroxychloroquine for 7 days or no antiviral treatment (non-placebo controlled). No significant differences were found in the mean reduction of viral load at day 3 or day 7, in the risk of hospitalization, or the time to complete resolution of symptoms.[65719]
  • A multicenter, randomized, open-label, three-group, controlled trial (n = 504) included adult hospitalized patients with suspected or confirmed COVID-19 who were not on supplemental oxygen or were receiving a maximum of 4 L/minute of supplemental oxygen. Patients received either standard care, standard care plus hydroxychloroquine for 7 days, or standard care plus hydroxychloroquine and azithromycin for 7 days. As compared to standard care, the proportional odds of having a higher (worse) score on the seven-point ordinal scale to assess clinical status at 15 days was not affected by either hydroxychloroquine alone or hydroxychloroquine plus azithromycin.[65741]
  • A multicenter comparative retrospective cohort study (n = 2,541) evaluated adult hospitalized patients with COVD-19 treated with hydroxychloroquine alone, hydroxychloroquine plus azithromycin, azithromycin alone, or treatment with neither agent (other treatments). Overall crude mortality rates were 18.1% overall, 13.5% for hydroxychloroquine alone group, 20.1% for hydroxychloroquine plus azithromycin group, 22.4% for azithromycin alone group, and 26.4% for other treatments (p less than 0.001). Steroids were administered to 68.2% of patients overall, 78.9% of patients in the hydroxychloroquine alone group, 74.3% of patients in the hydroxychloroquine plus azithromycin group, 38.8% of patients in the azithromycin alone group, and 35.7% of patients receiving other treatments (p less than 0.001). Patients in the hydroxychloroquine alone group had a 66% hazard ratio reduction and patients in the hydroxychloroquine plus azithromycin group had a 71% hazard ratio reduction compared to neither treatment (p less than 0.001).[65852]
  • A multicenter retrospective observational cohort study (n = 2,512) in hospitalized patients with COVID-19 analyzed the effect of hydroxychloroquine. There was no significant association between survival and any use of hydroxychloroquine during hospitalization, hydroxychloroquine alone, or hydroxychloroquine with azithromycin.[65853]
  • A multicenter randomized study (n = 194) in hospitalized patients with suspected and confirmed COVID-19 compared patients receiving hydroxychloroquine plus standard care (n = 97) to standard care alone (n = 97). After 28 days, there was no significant difference between the two groups regarding clinical outcome and the overall mortality risk was not significantly different between groups.[65915]
  • A randomized, controlled, open-label platform trial [i.e., Randomized Evaluation of COVid-19 thERapY (RECOVERY)] in hospitalized patients compared patients receiving hydroxychloroquine (n = 1,561) to usual care (n = 3,155). The primary outcome of 28-day mortality was not different between groups.[66021]
  • In an international, randomized, controlled platform trial (WHO Solidarity), there was no difference in in-hospital mortality between patients in the hydroxychloroquine arm (n = 954) and those in the control arm (n = 906). The hydroxychloroquine arm was halted for futility.[66045]
  • An observational, multicenter, cohort study assessed death on the COVID-19 ward and transfer to the ICU in hospitalized patients with moderate to severe COVID-19 receiving hydroxychloroquine (n = 189) compared to no treatment (n = 498). There was no significant difference between groups in the mortality rate. Hydroxychloroquine was associated with a significantly decreased risk of transfer to the ICU compared to controls.[66043]
  • In a prospective, randomized, blinded, placebo-controlled trial (n = 456), neither hydroxychloroquine nor hydroxychloroquine plus azithromycin demonstrated no difference in virologic cure in patients with mild or asymptomatic COVID-19.[66204]
  • In a multicenter, randomized, blinded, placebo-controlled trial (n = 479) of hospitalized patients with respiratory symptoms from COVID-19, the distribution of the 14 clinical status score (7-category ordinal scale; the COVID Outcomes Scale recommended by WHO) was not significant different for patients randomized to receive hydroxychloroquine (n = 242) compared to placebo (n = 237). The trial was stopped for futility.[66782]

 

Post-exposure and pre-exposure studies for COVID-19 with hydroxychloroquine have not reported benefit.

  • A randomized, double-blind, placebo-controlled trial (n = 132) of hospital-based healthcare workers showed no significant difference in infection rates in participants who received pre-exposure hydroxychloroquine compared to placebo.[66205]
  • In a randomized, double-blind, placebo-controlled trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, pre-exposure hydroxychloroquine prophylaxis once or twice weekly did not significantly reduce laboratory-confirmed COVID-19 or COVID-19-compatible illness.[66206]
  • In a randomized, double-blind, placebo-controlled trial (n = 821) that reviewed post-exposure prophylaxis with hydroxychloroquine within 4 days of exposure, the incidence of new illness did not differ significantly between groups.[66207]
  • A randomized, double-blind, placebo-controlled trial (n = 689) reviewed post-exposure prophylaxis with hydroxychloroquine within 96 hours of exposure showed no difference between groups in SARS-CoV-2 acquisition.[66208]
  • An open-label, cluster-randomized trial (n = 2314) involving asymptomatic contacts of PCR-positive COVID-19 patients compared post-exposure hydroxychloroquine prophylaxis to usual care. There was no difference between groups in the incidence of PCR-confirmed, symptomatic COVID-19 and the use of hydroxychloroquine was not associate with a lower incidence of SARS-CoV-2 transmission.[66209]

 

Additional data regarding clinical efficacy for COVID-19 are being evaluated.[65844]

Classifications

  • General Anti-infectives Systemic
    • Antiparasitic Agents, Insecticides, and Repellants
      • Antiprotozoals
        • Antimalarials
  • Musculo-Skeletal System
    • Antiinflammatory Agents and Antirheumatic Agents
      • Antiinflammatory and Antirheumatic Agents
        • Other Antiinflammatory and Antirheumatic Agents
Revision Date: 07/12/2021, 12:00:46 PM

References

41806 - Plaquenil (hydroxychloroquine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, Inc.; 2022 May.65171 - Food and Drug Administration (FDA). Chloroquine phosphate or hydroxychloroquine sulfate supplied from the strategic national stockpile for treatment of 2019 coronavirus disease: emergency use authorization letter. Retrieved March 30, 2020. Available on the World Wide Web at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#2019-ncov.65173 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of hydroxychloroquine sulfate supplied from the strategic national stockpile for treatment of COVID-19 in certain hospitalized patients. Retrieved March 30, 2020. Available on the World Wide Web at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#2019-ncov.65277 - Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ 2020;369:m1849.65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed November 10, 2022. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.65332 - Food and Drug Administration. FDA Drug Safety Communication: Hydroxychloroquine or chloroquine for COVID-19: FDA cautions against use outside of the hospital setting or a clinical trial due to risk of heart rhythm problems. Retrieved April 23, 2020. Available on the World Wide Web at: https://www.fda.gov/safety/medical-product-safety-information/hydroxychloroquine-or-chloroquine-covid-19-drug-safety-communication-fda-cautions-against-use?utm_campaign=FDA%20MedWatch%2065386 - Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with COVID-19. N Engl J Med 2020;382:2411-2418.65415 - Rosenberg ES, Dufort EM, Udo T, et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York state. JAMA 2020;323:2493-2502.65586 - Food and Drug Administration (FDA). Coronavirus (COVID-19) update: FDA revokes emergency use authorization for chloroquine and hydroxychloroquine. Retrieved June 15, 2020. Available on the World Wide Web at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and65718 - Skipper CP, Pastick KA, Engen NW, et al. Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial. Ann Int Med 2020;173:623-631.65719 - Mitja O, Corbacho-Monne M, Ubals M, et al. Hydroxychloroquine for early treatment of adults with mild Covid-19: A randomized-controlled trial. Clin Infect Dis. 2020.65741 - Cavalcanti AB, Zampieri FG, Rosa RG, et al. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. New Engl J Med 2020;383:2041-2052.65844 - ClinicalTrials.gov. National Institutes of Health (NIH) U.S. National Library of Medicine ClinicalTrials.gov website https://clinicaltrials.gov.65852 - Arshad S, Kilgore P, Chaudhry ZS, et al. Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19. Int J Infect Dis 2020;97:396-40365853 - Ip A, Berry DA, Hansen E, et al. Hydroxychloroquine and tocilizumab therapy in COVID-19 patients–an observational study. PLoS One 2020;15:e023769365915 - Abd-Elsalam S, Esmail ES, Khalaf M, et al. Hydroxychloroquine in the treatment of COVID-19: a multicenter randomized controlled study. Am J Trop Med Hyg 2020;103:1635-9.66021 - RECOVERY Collaborative Group, Horby P, Mafham M. Effect of hydroxychloroquine in hospitalized patients with Covid-19. New Engl J Med 2020;383:2030-40.66043 - Lammers AJJ, Brohet RM, Theunissen REP, et al. Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients. Int J Infect Dis 2020 Sep 29 [Epub ahead of print]66045 - WHO Solidarity Trial Consortium, Pan H, Peto R, et al. Repurposed antiviral drugs for COVID-19 - interim WHO Solidarity Trial results. N Engl JMed 2021;384:497-51166204 - Omrani AS, Pathan SA, Thomas SA, et al. Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19. EClinicalMedicine 2020;29:100645.66205 - Abella BS, Jolkovsky EL, Biney BT, et al. Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure SARS-CoV-2 prophylaxis among health care workers: a randomized clinical trial. JAMA Intern Med 2020;e206319.66206 - Rajasingham R, Bangdiwala AS, Nicol MR, et al. Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial. Clin Infect Dis 2020;ciaa1571.66207 - Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19. N Engl J Med 2020;383:517-25.66208 - Barnabas RV, Brown EF, Bershtyen A, et al. Hydroxychloroquine as postexposure prophylaxis to prevent severe acute respiratory syndrome coronavirus 2 infection: a randomized trial. Ann Intern Med 2020;M20-6519.66209 - Mitja O, Corbacho-Monne M, Ubals M, et al. A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19. N Engl J Med 2020:NEJMoa2021801. [Epub ahead of print]66782 - Self WH, Semler MW, Leither LM, et al. Effect of hydroxychloroquine on clinical status at 14 days in hospitalized patients with COVID-19: a randomized clinical trial. JAMA 2020;324:2165-76.

Administration Information

General Administration Information

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

Route-Specific Administration

Oral Administration

  • Administer with food or milk to minimize gastric indigestion or irritation.[41806]

Oral Solid Formulations

  • Crushing or dividing hydroxychloroquine tablets is not recommended per the FDA-approved product labeling.[41806]

Extemporaneous Compounding-Oral

Extemporaneous 25 mg/mL oral suspension (using tablets)†

NOTE: Extemporaneous compounding is not FDA-approved.[41806]

  • Remove the coating of hydroxychloroquine tablets, if necessary, with a towel moistened with alcohol.
  • Crush fifteen 200 mg hydroxychloroquine tablets into a fine powder in a mortar.
  • Add approximately 15 mL of the vehicle (e.g., Oral Mix or Oral Mix SF) to the mortar and levigate to form a fine paste.
  • Add the vehicle in geometric portions almost to volume and mix thoroughly after each addition.
  • Transfer the contents of the mortar to a graduated cylinder.
  • Rinse the mortar and pestle using a small amount of vehicle and transfer to the graduated cylinder.
  • Add enough vehicle to bring the final volume to 120 mL and transfer to an amber bottle.
  • Storage: The suspension is stable for 112 days under refrigeration (4 degrees C) or at room temperature (25 degrees C).[65138][65145]

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
Revision Date: 05/11/2021, 09:19:55 AMCopyright 2004-2022 by Lawrence A. Trissel. All Rights Reserved.

References

41806 - Plaquenil (hydroxychloroquine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, Inc.; 2022 May.65138 - McHenry AR, Wempe WF, Rice PJ. Stability of extemporaneously prepared hydroxychloroquine sulfate 25-mg/mL suspensions in plastic bottles and syringes. Int J Pharm Compd 2017;21:251-254.65145 - Michigan Collaborative Standardization of Compounded Oral Liquids. Hydroxychloroquine Oral Suspension. Available on the world wide web at: https://www.mipedscompounds.org/sites/default/files/standard-formulations/Hydroxychloroquine.pdf. Accessed March 20, 2020.

Adverse Reactions

Severe

  • acute generalized exanthematous pustulosis (AGEP)
  • agranulocytosis
  • angioedema
  • aplastic anemia
  • AV block
  • bronchospasm
  • cardiomyopathy
  • cardiotoxicity
  • corneal opacification
  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
  • erythema multiforme
  • exfoliative dermatitis
  • hearing loss
  • heart failure
  • hemolytic anemia
  • hepatic failure
  • macular degeneration
  • nephrotoxicity
  • porphyria
  • pulmonary hypertension
  • retinopathy
  • seizures
  • Stevens-Johnson syndrome
  • suicidal ideation
  • torsade de pointes
  • toxic epidermal necrolysis
  • ventricular fibrillation
  • ventricular tachycardia
  • visual impairment

Mild

  • abdominal pain
  • alopecia
  • anorexia
  • diarrhea
  • dizziness
  • emotional lability
  • fatigue
  • hair discoloration
  • headache
  • irritability
  • nausea
  • nightmares
  • photosensitivity
  • pruritus
  • rash
  • retinal pigment changes
  • skin discoloration
  • tinnitus
  • tremor
  • urticaria
  • vertigo
  • vomiting
  • weakness
  • weight loss

Moderate

  • anemia
  • ataxia
  • bone marrow suppression
  • bundle-branch block
  • corneal edema
  • depression
  • dyskinesia
  • dystonic reaction
  • hemolysis
  • hypoglycemia
  • leukopenia
  • myopathy
  • nystagmus
  • ocular toxicity
  • peripheral neuropathy
  • proteinuria
  • psoriasis
  • psychosis
  • QT prolongation
  • scotomata
  • thrombocytopenia

Hydroxychloroquine can cause ocular toxicity including irreversible retinal damage related to cumulative dose and treatment duration. A baseline ocular exam should be performed within the first year of hydroxychloroquine treatment. This baseline exam should include best corrected distance visual acuity (BCVA), an automated threshold visual field (VF) of the central 10 degrees (with retesting if an abnormality is noted), and spectral domain ocular coherence tomography (SD-OCT). Annual exams are recommended for patients at higher risk of retinal damage. For patients without significant risk factors, annual exams may be deferred until 5 years of treatment. In Asian patients, retinal toxicity may first be noticed outside the macula; therefore, visual field testing should be performed in the central 24 degrees instead of the central 10 degrees. Discontinue hydroxychloroquine if ocular toxicity is suspected and monitor the patient closely for ocular disease (i.e., retinal changes) and visual disturbance which may progress even after discontinuation of therapy. Other ocular adverse events include retinopathy, retinal pigment changes (bull's eye appearance), visual field defects/visual impairment (paracentral scotomata), macular degeneration, decreased dark adaptation, corneal edema, and corneal opacification.[41806]

Serious skin reaction have been reported with the use of hydroxychloroquine and include Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), photosensitivity, and acute generalized exanthematous pustulosis (AGEP). Monitor for serious skin reactions, especially in patients receiving a drug that may also induce dermatitis. Patients should seek medical attention if they experience signs and symptoms of serious skin reactions, including blisters on the skin, eyes, lips, or inside the mouth; itching or burning; with or without fever. Other allergic or dermatologic reactions include Other allergic and dermatologic reactions have been reported with the use of hydroxychloroquine. These include alopecia, hair color changes (hair discoloration), rash, pruritus, photosensitivity, hyperpigmentation (skin discoloration), exfoliative dermatitis, erythema multiforme, urticaria, angioedema, and bronchospasm.[41806]

Hydroxychloroquine may precipitate a severe attack of psoriasis that may be associated with pyrexia and hyperleukocytosis. Hydroxychloroquine may also exacerbate or precipitate porphyria.[41806]

Skeletal muscle myopathy or peripheral neuropathy leading to progressive weakness and atrophy of proximal muscle groups, depression of tendon reflexes, and abnormal nerve conduction has been reported. Muscle and nerve biopsies have been associated with curvilinear bodies and muscle fiber atrophy with vacuolar changes. Muscle and nerve biopsies have showed associated phospholipidosis. Drug-induced phospholipidosis may occur in other organ systems. Assess muscle strength and deep tendon reflexes periodically in patients on long-term therapy with hydroxychloroquine. If muscle or nerve toxicity is suspected or demonstrated by tissue biopsy, discontinue hydroxychloroquine therapy.[41806]

Hematological adverse reactions of hydroxychloroquine include myelosuppression (bone marrow suppression), including anemia, aplastic anemia, agranulocytosis, leukopenia, and thrombocytopenia. Hemolysis/hemolytic anemia has been reported in individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Monitor blood cell counts periodically if patients are given prolonged hydroxychloroquine therapy. If myelosuppression develops which is not attributable to the disease under treatment occurs, discontinue hydroxychloroquine.[41806]

Sensorineural hearing loss and tinnitus have been reported with hydroxychloroquine or other 4-aminoquinolines.[41806]

Fatal and life-threatening cases of cardiotoxicity, including cardiomyopathy, have been reported in patients treated with hydroxychloroquine. Signs and symptoms of cardiac compromise have occurred during acute and chronic treatment with the drug. Patients may present with ventricular hypertrophy, pulmonary hypertension, and conduction disorders including sick sinus syndrome. ECG findings include AV block or right or left bundle-branch block. In multiple cases, endomyocardial biopsy revealed an association of cardiomyopathy with phospholipidosis in absence of inflammation, infiltration, or necrosis. Drug-induced phospholipidosis may occur with other organs. Chronic toxicity should be considered when conduction disorders or biventricular hypertrophy are diagnosed. If cardiotoxicity is suspected or demonstrated by tissue biopsy, prompt discontinuation of hydroxychloroquine may prevent life-threatening cardiac complications. Additionally, hydroxychloroquine causes QT prolongation. The magnitude of QT prolongation may increase with increasing drug concentrations. Ventricular arrhythmias (i.e., ventricular fibrillation, ventricular tachycardia) and torsade de pointes have been reported in patients taking hydroxychloroquine. Monitor the ECG and cardiac function as indicated during hydroxychloroquine therapy. Cardiac disorders reported with the class of 4-aminoquinoline drugs postmarketing have included cardiomyopathy, heart failure, QT-interval prolongation, ventricular tachycardia, torsade de pointes, AV block, bundle-branch block, sick sinus syndrome, and pulmonary hypertension.[41806]

Adverse gastrointestinal (GI) effects reported with hydroxychloroquine or other 4-aminoquinolines include nausea, vomiting, abdominal pain, diarrhea, and anorexia. These effects are associated with oral administration and can be minimized by taking hydroxychloroquine with food. Abnormal liver function tests and fulminant hepatic failure have also been reported.[41806]

Suicidal ideation/behavior has been reported in patients treated with hydroxychloroquine. Other CNS or psychiatric adverse reactions reported with hydroxychloroquine or other 4-aminoquinolines include headache, dizziness, affect/emotional lability, irritability, psychosis, nervousness, nightmares, vertigo, nystagmus, ataxia, seizures, and extrapyramidal disorders such as dystonic reaction, dyskinesia, and tremor. Assess the risk and benefit of continued treatment in patients who develop neuropsychiatric reactions, including new or worsening depression, suicidal thoughts or behavior, or mood changes.[41806]

Weight loss and fatigue have been reported with the use of hydroxychloroquine or other 4-aminoquinolines.[41806]

Hydroxychloroquine has been shown to cause severe hypoglycemia including loss of consciousness that could be life threatening in patients treated with or without antidiabetic medications. Monitor blood glucose and adjust treatment as necessary in patients presenting with clinical symptoms of hypoglycemia during hydroxychloroquine treatment.[41806]

Hydroxychloroquine may cause nephrotoxicity. Cases of proteinuria with or without a moderate reduction in glomerular filtration rate have been reported with hydroxychloroquine therapy. Renal biopsy revealed phospholipidosis without immune deposits, inflammation, and/or increased cellularity. Phospholipidosis may be considered as a potential cause of renal injury in patients receiving hydroxychloroquine with underlying connective tissue disorders. Drug-induced phospholipidosis may occur in other organ systems. If renal toxicity is suspected or demonstrated by tissue biopsy, discontinue hydroxychloroquine.[41806]

Revision Date: 05/09/2022, 11:41:13 AM

References

41806 - Plaquenil (hydroxychloroquine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, Inc.; 2022 May.

Contraindications/Precautions

Absolute contraindications are italicized.

  • agranulocytosis
  • apheresis
  • aplastic anemia
  • Asian patients
  • AV block
  • behavioral changes
  • bone marrow suppression
  • bradycardia
  • breast-feeding
  • cardiac disease
  • cardiomyopathy
  • cardiotoxicity
  • celiac disease
  • depression
  • diabetes mellitus
  • females
  • fever
  • G6PD deficiency
  • geriatric
  • heart failure
  • hemolytic anemia
  • hepatic disease
  • human immunodeficiency virus (HIV) infection
  • hyperparathyroidism
  • hypocalcemia
  • hypoglycemia
  • hypokalemia
  • hypomagnesemia
  • hypothermia
  • hypothyroidism
  • leukopenia
  • long QT syndrome
  • myocardial infarction
  • myopathy
  • nephrotoxicity
  • neurological disease
  • ocular disease
  • ocular toxicity
  • peripheral neuropathy
  • pheochromocytoma
  • porphyria
  • pregnancy
  • psoriasis
  • QT prolongation
  • renal disease
  • renal impairment
  • rheumatoid arthritis
  • serious rash
  • sickle cell disease
  • sleep deprivation
  • stroke
  • systemic lupus erythematosus (SLE)
  • thrombocytopenia
  • ventricular arrhythmias
  • visual disturbance

Fatal and life-threatening cases of cardiotoxicity, including cardiomyopathy, have been reported in patients treated with hydroxychloroquine. Signs and symptoms of cardiac compromise have occurred with acute and chronic hydroxychloroquine therapy. In multiple cases, endomyocardial biopsy revealed an association of cardiomyopathy with phospholipidosis in absence of inflammation, infiltration, or necrosis. Drug-induced phospholipidosis may occur in other organs. Consider chronic toxicity when conduction disorders (bundle-branch block, AV block) or biventricular hypertrophy are diagnosed. If cardiotoxicity is suspected or demonstrated by tissue biopsy, prompt discontinuation of hydroxychloroquine may prevent life-threatening cardiac complications.[41806] Hydroxychloroquine has a;sp caused fatal and life-threatening cases of ventricular arrhythmias. Hydroxychloroquine prolongs the QT interval; the magnitude of QT prolongation may increase with increasing drug concentrations. Avoid hydroxychloroquine in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, proarrhythmic conditions (e.g. bradycardia), AV block, cardiac disease, heart failure, stress-related cardiomyopathy, myocardial infarction, history of ventricular arrhythmias, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.[41806] [28432] [28457] [56592] [65180] In patients taking hydroxychloroquine with another drug that also prolongs the QT interval (see Therapeutic Drug Monitoring for recommendations specific to azithromycin with hydroxychloroquine used together for COVID-19), obtain a pre-treatment QTc using a standard 12-lead ECG, telemetry, or mobile ECG device. Obtain baseline electrolytes, including calcium, magnesium, and potassium. Determine if the patient is currently on any QT-prolonging medications that can be discontinued. Document high-risk cardiovascular and comorbid conditions. If the baseline QTc is 500 msec or more and/or the patient has an inherent tendency to develop an exaggerated QTc response (i.e., change of 60 msec or more), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and proceed with close QTc surveillance. Obtain an initial on-therapy QTc approximately 2 to 4 hours after the first dose and then again at 48 and 96 hours after treatment initiation. If the baseline QTc is 460 to 499 msec (prepubertal), 470 to 499 msec (postpubertal males), or 480 to 499 msec (postpubertal females), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and obtain an initial on-therapy QTc 48 and 96 hours after treatment initiation. If the baseline QTc is less than 460 msec (prepubertal), less than 470 msec (postpubertal males), or less than 480 msec (postpuberal females), correct electrolyte abnormalities and obtain an initial on-therapy QTc 48 and 96 hours after treatment initiation.[65170]

Severe and irreversible retinal toxicity has been reported with the use of hydroxychloroquine and ocular toxicity is related to cumulative dosage and treatment duration. Risk factors for retinal damage include daily doses more than 6.5 mg/kg (5 mg/kg base) of actual body weight, durations of use greater than 5 years, renal dysfunction, use of concomitant drugs such as tamoxifen, and concurrent macular ocular disease. A baseline ocular exam should be performed within the first year of hydroxychloroquine treatment. This baseline exam should include best corrected distance visual acuity (BCVA), an automated threshold visual field (VF) of the central 10 degrees (with retesting if an abnormality is noted), and spectral domain ocular coherence tomography (SD-OCT). Annual exams, which include BCVA, VF, and SD-OCT, are recommended for patients at higher risk of retinal damage. For patients without significant risk factors, annual ocular exams may be deferred until 5 years of treatment. In Asian patients, retinal toxicity may first be noticed outside the macula; therefore, visual field testing should be performed in the central 24 degrees instead of the central 10 degrees. Discontinue hydroxychloroquine if ocular toxicity is suspected and monitor the patient closely for retinal changes and visual disturbance which may progress even after discontinuation of therapy.[41806]

Hydroxychloroquine is contraindicated in patients with known hypersensitivity to 4-aminoquinoline compounds.[41806] Serious adverse reactions have been reported with the use of hydroxychloroquine including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP). Monitor for serious skin reactions, especially in patients receiving a drug that may also induce dermatitis. Advise patients to seek medical attention promptly if they experience signs and symptoms of serious rash or skin reactions such as blisters on the skin, eyes, lips or in the mouth, itching or burning, with or without fever. Discontinue hydroxychloroquine if these severe reactions occur.[41806]

Avoid hydroxychloroquine in patients with psoriasis or porphyria unless the benefit to the patients outweighs the possible risk. Hydroxychloroquine has been shown to precipitate severe flare-ups of psoriasis and exacerbate porphyria.[41806]

Hydroxychloroquine may cause bone marrow suppression including aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia. Monitor blood cell counts periodically in patients on prolonged therapy. If a treated patient develops myelosuppression that cannot be attributable to the disease, discontinue the drug. Administer hydroxychloroquine with caution in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) due to the risk of hemolysis. Monitor for hemolytic anemia, especially in patients taking other drugs associated with hemolysis.[41806]

Hydroxychloroquine should be used with caution in patients with neurological disease, peripheral neuropathy, or myopathy. Skeletal muscle myopathy or peripheral neuropathy leading to progressive weakness and atrophy of proximal muscle groups, depressed tendon reflexes, and abnormal nerve conduction have been reported. Muscle and nerve biopsies have shown associated phospholipidosis. Drug-induced phospholipidosis may occur in other organ systems. Assess muscle strength and deep tendon reflexes periodically in patients on long-term therapy with hydroxychloroquine. Advise patients to report any symptoms of muscle weakness. If muscle or nerve toxicity is suspected or demonstrated by tissue biopsy, discontinue hydroxychloroquine therapy.[41806]

Alert patients to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts, or mood or behavioral changes. The risk and benefit of continued treatment with hydroxychlorquine should be assessed for patients who develop these symptoms. Suicidal behavior has been reported in patients treated with hydroxychlorquine.[41806]

A reduction in the dosage of hydroxychloroquine may be necessary in patients with renal disease. Renal impairment is a risk factor for retinal damage due to hydroxychloroquine, which is related to cumulative dosage and treatment duration. Hydroxychloroquine has been associated with nephrotoxicity. Cases of proteinuria with or without a moderate reduction in glomerular filtration rate have been reported with hydroxychloroquine therapy. Renal biopsy revealed phospholipidosis without immune deposits, inflammation, and/or increased cellularity. Phospholipidosis may be considered as a potential cause of renal injury in patients receiving hydroxychloroquine with underlying connective tissue disorders. Drug-induced phospholipidosis may occur in other organ systems. If renal toxicity is suspected or demonstrated by tissue biopsy, discontinue hydroxychloroquine.[41806]

Hydroxychloroquine should be used with caution in patients with hepatic disease. A dose reduction may be necessary.[41806]

Use hydroxychloroquine with caution in patients with hypoglycemia or diabetes mellitus. Hydroxychloroquine can cause severe, life-threatening hypoglycemia in patients treated with or without antidiabetic medications. Warn patients about the risk of hypoglycemia and the associated clinical signs and symptoms. Monitor blood glucose and adjust treatment as necessary in patients presenting with clinical symptoms of hypoglycemia during hydroxychloroquine treatment.[41806]

Prolonged clinical experience over decades of use and available data from published epidemiologic and clinical studies with hydroxychloroquine use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Hydroxychloroquine readily crosses the placenta with cord blood levels corresponding to maternal plasma levels. No retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in children who were exposed to hydroxychloroquine in utero. Available epidemiologic and clinical studies have methodological limitations including small sample size and study design. There are risks to the mother and fetus associated with untreated or increased maternal disease activity from malaria, rheumatoid arthritis, and systemic lupus erythematosus (SLE) during pregnancy that should be considered. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to hydroxychloroquine during pregnancy. Encourage patients to register by contacting 1-877-311-8972.[41806] Hydroxychloroquine is considered to be compatible for use during pregnancy in some anti-rheumatic guidelines, and may be continued in pregnancy for maintenance of remission or treatment of a disease flare.[62180] [64661] [64662] Hydroxychloroquine may also be appropriate for pregnancies complicated by lupus.[34349] [34358] Guidelines also recommend hydroxychloroquine as an alternative to chloroquine as a treatment option for acute malaria and for prophylaxis in pregnant women during all trimesters.[63990] [64059] Animal reproductive studies have not been conducted.[41806]

Data regarding the use of hydroxychloroquine during breast-feeding report that hydroxychloroquine is present in human milk at low levels. No adverse reactions have been reported in breastfed infants. No retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in children who were exposed to hydroxychloroquine through breastmilk. There is no information on the effect of hydroxychloroquine on milk production.[41806] Hydroxychloroquine is considered to be compatible for use during breast-feeding in some anti-rheumatic guidelines, and may be continued during lactation for maintenance of remission or treatment of a disease flare.[62180] [64661] [64662] During lactation studies, breast milk concentrations ranged from 10.6 to 1,392 mcg/L  and breast-fed infants would likely receive 0.2 mg/kg or less of hydroxychloroquine.[48476] [48477] [48478] [48479] In infants monitored for up to at least 1 year of age, careful follow-up found no adverse effects on growth, vision, or hearing.[48474] [48475] The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for the medication and any potential adverse effects on the breastfed child from hydroxychloroquine exposure or from the underlying maternal condition.[41806]

Revision Date: 05/09/2022, 12:06:22 PM

References

28432 - Roden, DM. Drug-induced prolongation of the QT interval. New Engl J Med 2004;350:1013-22.28457 - Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003;23:881-908.34349 - Bertsias G, Ioannidis JPA, Boletis J, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a task force of the EULAR standing committee for international clinical studies including therapeutics. Ann Rheum Dis 2008;67:195-205.34358 - Levy RA, Vilela VS, Cataldo MJ, et al. Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study. Lupus 2001;10:401-4.41806 - Plaquenil (hydroxychloroquine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, Inc.; 2022 May.48474 - Cimaz R, Brucato A, Meregalli E et al. Electroretinograms of children born to mothers treated with hydroxychloroquine during pregnancy and breast-feeding: comment on the article by Costedoat-Chalumeau et al. Arthritis Rheum. 2004;50:3056-7. PMID48475 - Motta M, Tincani A, Faden D et al. Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation. J Perinatol. 2005;25:86-9.48476 - Ostensen M, Brown ND, Chiang PK et al. Hydroxychloroquine in human breast milk. Eur J Clin Pharmacol. 1985; 28:357.48477 - Nation RL, Hackett LP, Dusci LJ et al. Excretion of hydroxychloroquine in human milk. Br J Clin Pharmacol. 1984;17:368-9.48478 - Costedoat-Chalumeau N, Amoura Z, Aymard G et al. Evidence of transplacental passage of hydroxychloroquine in humans. Arthritis Rheum. 2002;46:1123-4.48479 - Costedoat-Chalumeau N, Amoura Z, Sebbough D et al. Electroretinograms of children born to mothers treated with hydroxychloroquine during pregnancy and breast-feeding: comment on the article by Costedoat-Chalumeau et al. Author reply. Arthritis Rheum. 2004;50:3057-8.56592 - van Noord C, Eijgelsheim M, Stricker BH. Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol 2010;70(1):16-23.62180 - Gotestam Skorpen C, Hoeltzenbein M, Tincani A, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016;75(5):795-810.63990 - Arguin PM, Tan KR. Chapter 3. Infectious diseases related to travel. Malaria. In. Centers for Disease Control and Prevention. 2018 Yellow Book - Traveler's Health. Atlanta: U.S. Department of Health and Human Services, Public Health Service. https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/malaria64059 - Centers for Disease Control and Prevention. Treatment of malaria (guidelines for clinicians). Atlanta, GA: US Department of Health and Human Services; 2019. https://www.cdc.gov/malaria/diagnosis_treatment/treatment.html.64661 - de Jong PHP, Dolhain RJEM. Fertility, pregnancy, and lactation in rheumatoid arthritis. Rheum Dis Clin N Am 2017;43:227-237.64662 - ACOG Committee on Obstetric Practice. ACOG Committee Opinion No. 776: immune modulating therapies in pregnancy and lactation. Obstet Gynecol 2019;133:e287-e295.65170 - Giudicessi JR, Noseworthy PA, Friedman PA, Ackerman MJ. Urgent guidance for navigating and circumventing the QTc prolonging and torsadogenic potential of possible pharmacotherapies for COVID-19 [published online ahead of print, March 25, 2020]. Mayo Clin Proc 2020;95.65180 - Woosley RL, Heise CW, Gallo T, et al. QTFactors List. Oro Valley, AZ: AZCERT, Inc.; Accessed March 31, 2020. Available on the World Wide Web at: https://crediblemeds.org/ndfa-list/

Mechanism of Action

Hydroxychloroquine, a 4-aminoquinolone antimalarial, is a weak base and may exert its antimalarial effect by concentrating in the acid vesicles of the plasmodia and by inhibiting the polymerization of heme. It can also inhibit certain enzymes by its interaction with DNA. Organisms with reduced susceptibilities to chloroquine also show reduced susceptibilities to hydroxychloroquine.[41806]

 

Although the mechanisms underlying the antiinflammatory and immunomodulatory effects of hydroxychloroquine in the treatment of rheumatoid arthritis, chronic discoid lupus erythematous, and systemic lupus erythematosus are not fully known, several possible mechanisms of action have been proposed. It is unclear if these mechanisms work similarly for rheumatic and autoimmune diseases. Potential mechanisms include reduced cytokine production, inhibition of immune effector cells, inhibition of platelet function, protection of the cell surface from external disturbances, competitive binding to nucleic acid ligands or toll-like receptors (TLRs), interference with lysosomal function, reduction of leakage of lysosomal enzymes, and interference with endosomal NADPH oxidase (NOX).[41806] [61727] [61728] [61729]

 

There are several potential mechanisms by which hydroxychloroquine may be active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These include inhibition of viral enzymes or processes such as viral DNA and RNA polymerase, viral protein glycosylation, virus assembly, new virus particle transport, and virus release. Other mechanisms may also involve ACE2 cellular receptor inhibition, acidification at the surface of the cell membrane inhibiting fusion of the virus, and immunomodulation of cytokine release.[61729] [61732] [65120] [65121] [65139] [65140] [65141] [65142] [65143]

Revision Date: 05/14/2021, 01:00:56 PM

References

41806 - Plaquenil (hydroxychloroquine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, Inc.; 2022 May.61727 - Muller-Calleja N, Manukyan D, Canisius A, et al. Hydroxychloroquine inhibits proinflammatory signalling pathways by targeting endosomal NADPH oxidase. Ann Rheum Dis 2016. Epub ahead of print, doi: 10.1136/annrheumdis-2016-210012.61728 - Kuznik A, Bencina M, Svajger U, et al. Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J Immunol 2011;186:4794-804.61729 - Fox R. Anti-malarial drugs: possible mechanisms of action in autoimmune disease and prospects for drug development. Lupus 1996;S1:S4-10.61732 - Ben-Zvi H, Kivity S, Langevitz P, et al. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol 2012;42:145-53.65120 - Wang M, Cao R, Zhang L, et al. Remdesivir and Chloroquine Effectively Inhibit the Recently Emerged Novel Coronavirus (2019-nCoV) in Vitro. Cell Res 2020;30(3):269-271.65121 - Yao X, Fei Y, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020 Mar 9. [Epub ahead of print]65139 - Fox RI. Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum 1993;23(2 S1):82-91.65140 - Savarino A, Trani LD, Donatelli I, et al. New insights into the antiviral effects of chloroquine. The Lancet 2006;6:67-9.65141 - Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005;2:69.65142 - Cortegiani A, Ingoglia G, Ippolito M, et al. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care 2020. [In press]65143 - Cohen SN, Yielding KL. Inhibition of DNA and RNA polymerase reactions by chloroquine. Proc Natl Acad Sci U S A 1965; 54: 521-7.

Pharmacokinetics

Hydroxychloroquine is administered orally. It is widely distributed into body tissues, with high concentrations in the bone marrow, liver, kidneys, lungs, adrenal gland, and pituitary gland. Hydroxychloroquine has a high affinity for melanin and thus is concentrated in the choroid and ciliary body of the eye, which may account for the retinal toxicity. Cellular concentrations have been shown to be higher in mononuclear cells than in polymorphonuclear leukocytes.[41806] [61731] [61732]

 

Hydroxychloroquine is partially metabolized in the liver to 3 metabolites. These include the major metabolite, desethylhydroxychloroquine (DHCQ), as well as desethylchloroquine (DCQ) and bidesethylhydroxychloroquine (BDCQ). Renal clearance of unchanged drug ranges from 16% to 30% and does not change with chronic dosing. A half-life of 123.5 days in plasma were observed after a single 200 mg dose in healthy male volunteers. Urine hydroxychloroquine levels were still detectable after 3 months with approximately 10% of the dose excreted as parent drug. Results after a single 200 mg oral dose versus a single 155 mg IV dose demonstrated a half-life of about 40 days and large volume of distribution. After chronic oral administration, the absorption half-life was approximately 3 to 4 hours and th terminal half-life ranged form 40 to 50 days.[41806]

 

Affected cytochrome P450 isoenzymes and drug transporters: CYP2C8, CYP2D6, CYP3A4, P-gp

In vitro data suggest that hydroxychloroquine is metabolized primarily by CYP2C8 and CYP3A4, and to a much lesser extent, by CYP2D6.[65236] [65239] It has also been shown to be an inhibitor of the drug transporter P-glycoprotein (P-gp).[65237]

Route-Specific Pharmacokinetics

Oral Route

Bioavailability is approximately 74%. Hydroxychloroquine displays linear kinetics. Tmax was 3.3 to 3.7 hours. Peak blood concentrations of metabolites were observed at the same time as peak hydroxychloroquine levels. In rheumatoid arthritis patients, there is a large variability in absorption (30% to 100%) with mean concentrations significantly higher in patients with less disease activity.[41806]

Special Populations

Renal Impairment

Renal clearance does not correlate with creatinine clearance.[41806]

Revision Date: 05/14/2021, 01:23:32 PM

References

41806 - Plaquenil (hydroxychloroquine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, Inc.; 2022 May.61731 - Mackenzie AH. Pharmacologic actions of 4-aminoquinoline compounds. Am J Med 1983;75:5-10.61732 - Ben-Zvi H, Kivity S, Langevitz P, et al. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol 2012;42:145-53.65236 - Schrezenmeier E, Dorner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Rheumatology 2020;16:155-166.65237 - Tiberghien F, Loor F. Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry screening assay. Anti-Cancer Drugs 1996;7:568-578.65239 - Projean D, Baune B, Farinotti R, et al. In vitro metabolism of chloroquine: Identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation. Drug Metab Dispos 2003;31:748-754.

Pregnancy/Breast-feeding

pregnancy

Prolonged clinical experience over decades of use and available data from published epidemiologic and clinical studies with hydroxychloroquine use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Hydroxychloroquine readily crosses the placenta with cord blood levels corresponding to maternal plasma levels. No retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in children who were exposed to hydroxychloroquine in utero. Available epidemiologic and clinical studies have methodological limitations including small sample size and study design. There are risks to the mother and fetus associated with untreated or increased maternal disease activity from malaria, rheumatoid arthritis, and systemic lupus erythematosus (SLE) during pregnancy that should be considered. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to hydroxychloroquine during pregnancy. Encourage patients to register by contacting 1-877-311-8972.[41806] Hydroxychloroquine is considered to be compatible for use during pregnancy in some anti-rheumatic guidelines, and may be continued in pregnancy for maintenance of remission or treatment of a disease flare.[62180] [64661] [64662] Hydroxychloroquine may also be appropriate for pregnancies complicated by lupus.[34349] [34358] Guidelines also recommend hydroxychloroquine as an alternative to chloroquine as a treatment option for acute malaria and for prophylaxis in pregnant women during all trimesters.[63990] [64059] Animal reproductive studies have not been conducted.[41806]

breast-feeding

Data regarding the use of hydroxychloroquine during breast-feeding report that hydroxychloroquine is present in human milk at low levels. No adverse reactions have been reported in breastfed infants. No retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in children who were exposed to hydroxychloroquine through breastmilk. There is no information on the effect of hydroxychloroquine on milk production.[41806] Hydroxychloroquine is considered to be compatible for use during breast-feeding in some anti-rheumatic guidelines, and may be continued during lactation for maintenance of remission or treatment of a disease flare.[62180] [64661] [64662] During lactation studies, breast milk concentrations ranged from 10.6 to 1,392 mcg/L  and breast-fed infants would likely receive 0.2 mg/kg or less of hydroxychloroquine.[48476] [48477] [48478] [48479] In infants monitored for up to at least 1 year of age, careful follow-up found no adverse effects on growth, vision, or hearing.[48474] [48475] The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for the medication and any potential adverse effects on the breastfed child from hydroxychloroquine exposure or from the underlying maternal condition.[41806]

Revision Date: 05/09/2022, 10:10:49 AM

References

34349 - Bertsias G, Ioannidis JPA, Boletis J, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a task force of the EULAR standing committee for international clinical studies including therapeutics. Ann Rheum Dis 2008;67:195-205.34358 - Levy RA, Vilela VS, Cataldo MJ, et al. Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study. Lupus 2001;10:401-4.41806 - Plaquenil (hydroxychloroquine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, Inc.; 2022 May.48474 - Cimaz R, Brucato A, Meregalli E et al. Electroretinograms of children born to mothers treated with hydroxychloroquine during pregnancy and breast-feeding: comment on the article by Costedoat-Chalumeau et al. Arthritis Rheum. 2004;50:3056-7. PMID48475 - Motta M, Tincani A, Faden D et al. Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation. J Perinatol. 2005;25:86-9.48476 - Ostensen M, Brown ND, Chiang PK et al. Hydroxychloroquine in human breast milk. Eur J Clin Pharmacol. 1985; 28:357.48477 - Nation RL, Hackett LP, Dusci LJ et al. Excretion of hydroxychloroquine in human milk. Br J Clin Pharmacol. 1984;17:368-9.48478 - Costedoat-Chalumeau N, Amoura Z, Aymard G et al. Evidence of transplacental passage of hydroxychloroquine in humans. Arthritis Rheum. 2002;46:1123-4.48479 - Costedoat-Chalumeau N, Amoura Z, Sebbough D et al. Electroretinograms of children born to mothers treated with hydroxychloroquine during pregnancy and breast-feeding: comment on the article by Costedoat-Chalumeau et al. Author reply. Arthritis Rheum. 2004;50:3057-8.62180 - Gotestam Skorpen C, Hoeltzenbein M, Tincani A, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016;75(5):795-810.63990 - Arguin PM, Tan KR. Chapter 3. Infectious diseases related to travel. Malaria. In. Centers for Disease Control and Prevention. 2018 Yellow Book - Traveler's Health. Atlanta: U.S. Department of Health and Human Services, Public Health Service. https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/malaria64059 - Centers for Disease Control and Prevention. Treatment of malaria (guidelines for clinicians). Atlanta, GA: US Department of Health and Human Services; 2019. https://www.cdc.gov/malaria/diagnosis_treatment/treatment.html.64661 - de Jong PHP, Dolhain RJEM. Fertility, pregnancy, and lactation in rheumatoid arthritis. Rheum Dis Clin N Am 2017;43:227-237.64662 - ACOG Committee on Obstetric Practice. ACOG Committee Opinion No. 776: immune modulating therapies in pregnancy and lactation. Obstet Gynecol 2019;133:e287-e295.

Interactions

Level 1 (Severe)

  • Cisapride
  • Dronedarone
  • Ketoconazole
  • Levoketoconazole
  • Pimozide
  • Thioridazine

Level 2 (Major)

  • Alfuzosin
  • Amiodarone
  • Amisulpride
  • Amoxicillin; Clarithromycin; Omeprazole
  • Anagrelide
  • Apomorphine
  • Aripiprazole
  • Arsenic Trioxide
  • Artemether; Lumefantrine
  • Asenapine
  • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
  • Atomoxetine
  • Azithromycin
  • Bedaquiline
  • Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
  • Bismuth Subsalicylate; Metronidazole; Tetracycline
  • Buprenorphine
  • Buprenorphine; Naloxone
  • Cabotegravir; Rilpivirine
  • Ceritinib
  • Chlorpromazine
  • Cimetidine
  • Ciprofloxacin
  • Citalopram
  • Clarithromycin
  • Clofazimine
  • Clozapine
  • Codeine; Phenylephrine; Promethazine
  • Codeine; Promethazine
  • Crizotinib
  • Cyclosporine
  • Dasatinib
  • Degarelix
  • Desflurane
  • Deutetrabenazine
  • Dextromethorphan; Quinidine
  • Disopyramide
  • Dofetilide
  • Dolasetron
  • Dolutegravir; Rilpivirine
  • Donepezil
  • Donepezil; Memantine
  • Droperidol
  • Efavirenz
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  • Isoflurane
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  • Isoniazid, INH; Rifampin
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  • Voclosporin
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  • Voriconazole
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Level 3 (Moderate)

  • Acarbose
  • Acetazolamide
  • Acetohexamide
  • Albiglutide
  • Alogliptin
  • Alogliptin; Metformin
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  • Calcium; Vitamin D
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  • Ertugliflozin
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  • Insulin Degludec; Liraglutide
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  • Lacosamide
  • Lamotrigine
  • Lente Insulin
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  • Linagliptin
  • Linagliptin; Metformin
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  • Lixisenatide
  • Lorazepam
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  • Metformin
  • Metformin; Repaglinide
  • Metformin; Rosiglitazone
  • Metformin; Saxagliptin
  • Metformin; Sitagliptin
  • Methotrexate
  • Methsuximide
  • Miglitol
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  • Pentobarbital
  • Perampanel
  • Phenobarbital
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  • Phentermine; Topiramate
  • Phenytoin
  • Pioglitazone
  • Pioglitazone; Glimepiride
  • Pioglitazone; Metformin
  • Pramlintide
  • Pregabalin
  • Primidone
  • Regular Insulin
  • Regular Insulin; Isophane Insulin (NPH)
  • Repaglinide
  • Rituximab
  • Rituximab; Hyaluronidase
  • Rosiglitazone
  • Rufinamide
  • Saxagliptin
  • Semaglutide
  • SGLT2 Inhibitors
  • Simvastatin; Sitagliptin
  • Sitagliptin
  • Sulfonylureas
  • Thiazolidinediones
  • Tiagabine
  • Tirzepatide
  • Tolazamide
  • Tolbutamide
  • Topiramate
  • Ultralente Insulin
  • Valproic Acid, Divalproex Sodium
  • Zonisamide

Level 4 (Minor)

  • Praziquantel
  • Telbivudine
Acarbose: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the alpha-glucosidase inhibitors, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent. [41806] Acetazolamide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as acetazolamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Acetohexamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Albiglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Alfuzosin: (Major) Avoid coadministration of alfuzosin and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Alfuzosin may prolong the QT interval in a dose-dependent manner. [28261] [41806] [65157] [65170] Alogliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Alpha-glucosidase Inhibitors: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the alpha-glucosidase inhibitors, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent. [41806] Amiodarone: (Major) Concomitant use of hydroxychloroquine and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation. [28224] [28432] [28457] [41806] [65170] Amisulpride: (Major) Avoid coadministration of amisulpride and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Amisulpride causes dose- and concentration-dependent QT prolongation. [41806] [65068] [65157] [65170] Amobarbital: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as amobarbital. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). [28225] [28238] [41806] [65157] [65170] Ampicillin: (Moderate) Administer oral ampicillin 2 hours before or 2 hours after hydroxychloroquine. Ampicillin bioavailability may be decreased with coadministration of hydroxychloroquine as a significant reduction in ampicillin bioavailability was observed with the structurally similar chloroquine in a study of healthy volunteers. The reduction of ampicillin bioavailability could be attributed to slower gastric emptying and enhancement of gut motility produced by chloroquine. [29758] [41806] [61761] Anagrelide: (Major) Avoid coadministration of anagrelide and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. [30163] [41806] [65157] [65170] Antacids: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [61758] Apomorphine: (Major) Avoid coadministration of apomorphine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. [28661] [41806] [59321] [65157] [65170] Aripiprazole: (Major) Concomitant use of hydroxychloroquine and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [42845] [65170] Arsenic Trioxide: (Major) Avoid coadministration of arsenic trioxide and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. [41806] [59438] [65157] [65170] Artemether; Lumefantrine: (Major) Avoid coadministration of artemether; lumefantrine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Artemether; lumefantrine is associated with prolongation of the QT interval. [34501] [41806] [65157] [65170] (Major) Avoid coadministration of artemether; lumefantrine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Artemether; lumefantrine is associated with prolongation of the QT interval. [35401] [41806] [65157] [65170] Asenapine: (Major) Avoid coadministration of asenapine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Asenapine has also been associated with QT prolongation. [36343] [41806] [65157] [65170] Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [61758] Atomoxetine: (Major) Concomitant use of hydroxychloroquine and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28405] [41806] [65170] Azithromycin: (Major) Concomitant use of hydroxychloroquine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28855] [41806] [65170] Bedaquiline: (Major) Avoid coadministration of bedaquline and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine and bedaquiline prolong the QT interval. Discontinue bedaquiline if evidence of serious ventricular arrhythmia or QTcF interval greater than 500 msec. [41806] [52746] [65157] [65170] Betrixaban: (Moderate) Use caution if hydroxychloroquine is coadministered with bextrixaban due to the potential for increased bextrixaban exposure which may increase the risk of bleeding. Bextrixaban is a P-gp substrate; limited data suggests that hydroxychloroquine is a P-gp inhibitor. [62037] [65210] Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [36894] [41806] [65170] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [36894] [41806] [65170] Brivaracetam: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as brivaracetam. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Buprenorphine: (Major) Concomitant use of hydroxychloroquine and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41235] [41806] [60270] [65170] Buprenorphine; Naloxone: (Major) Concomitant use of hydroxychloroquine and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41235] [41806] [60270] [65170] Cabotegravir; Rilpivirine: (Major) Avoid coadministration of rilpivirine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. [41806] [44376] [65157] [65170] Calcium Carbonate: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [61758] Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [61758] Calcium Carbonate; Magnesium Hydroxide: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [61758] Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [61758] Calcium Carbonate; Risedronate: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [61758] Calcium Carbonate; Simethicone: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [61758] Calcium; Vitamin D: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [61758] Canagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Carbamazepine: (Moderate) Monitor for a decrease in hydroxychloroquine and carbamazepine efficacy if coadministration is necessary. Antiepileptic drug activity may be impaired if coadministered with hydroxychloroquine and concomitant use may decrease exposure of hydroxychloroquine. Hydroxychloroquine is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. [41806] [56579] [65210] [65239] Ceritinib: (Major) Avoid coadministration of ceritinib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Hydroxychloroquine also prolongs the QT interval. [41806] [57094] [65157] [65170] Chlorpromazine: (Major) Avoid coadministration of chlorpromazine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Chlorpromazine is associated with an established risk of QT prolongation and torsade de pointes (TdP). [28415] [41806] [43065] [65157] [65170] Chlorpropamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Cimetidine: (Major) Avoid concomitant use of hydroxychloroquine and cimetidine as cimetidine may inhibit the metabolism of hydroxychloroquine, increasing its plasma concentration. This interaction has been observed on treatment with the structurally similar chloroquine and cannot be ruled out for hydroxychloroquine. [29396] [41806] [61759] [61760] Ciprofloxacin: (Major) Concomitant use of hydroxychloroquine and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [43411] [65170] Cisapride: (Contraindicated) Avoid concomitant use of hydroxychloroquine and cisapride due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [28978] [41806] [47221] Citalopram: (Major) Concomitant use of hydroxychloroquine and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28269] [41806] [65170] Clarithromycin: (Major) Avoid coadministration of clarithromycin and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). [28225] [28238] [41806] [65157] [65170] Clobazam: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as clobazam. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Clofazimine: (Major) Concomitant use of clofazimine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [63936] [65170] Clonazepam: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant clonazepam and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Clorazepate: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as clorazepate. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Clozapine: (Major) Avoid coadministration of clozapine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. [28262] [41806] [65157] [65170] Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [55578] [65170] Codeine; Promethazine: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [55578] [65170] Crizotinib: (Major) Avoid coadministration of crizotinib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib can cause concentration-dependent QT prolongation. Hydroxychloroquine also prolongs the QT interval. [41806] [45458] [65157] [65170] Cyclosporine: (Major) Closely monitor serum cyclosporine concentrations and adjust the dose of cyclosporine as appropriate after starting or stopping hydroxychloroquine therapy. Increased serum concentrations of cyclosporine have been noted when coadministered with hydroxychloroquine. Monitor patients for cyclosporine-related adverse events such as nephrotoxicity or hepatic toxicity. [41806] [65478] Dabigatran: (Moderate) Use caution if hydroxychloroquine is coadministered with dabigatran due to the potential for increased dabigatran exposure which may increase the risk of bleeding. Dabigatran is a P-gp substrate; limited data suggests that hydroxychloroquine is a P-gp inhibitor. [42121] [65210] Dapagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Dasatinib: (Major) Avoid coadministration of dasatinib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. [32387] [41806] [65157] [65170] Degarelix: (Major) Avoid coadministration of degarelix and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. [41806] [46869] [65157] [65170] Desflurane: (Major) Avoid coadministration of halogenated anesthetics and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both hydroxychloroquine and halogenated anesthetics can prolong the QT interval. [28457] [28458] [28754] [28755] [28756] [41806] [65157] [65170] Deutetrabenazine: (Major) Avoid coadministration of deutetrabenazine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. [41806] [61845] [65157] [65170] Dextromethorphan; Quinidine: (Major) Avoid coadministration of quinidine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). [41806] [42280] [47357] [65157] [65170] Diazepam: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant diazepam and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Digoxin: (Moderate) Monitor serum digoxin concentrations in patients receiving digoxin and hydroxychloroquine as coadministration may result in increased serum digoxin concentrations. [41806] Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Disopyramide: (Major) Avoid coadministration of disopyramide and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP). [28228] [41806] [65157] [65170] Dofetilide: (Major) Avoid coadministration of dofetilide and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Hydroxychloroquine also prolongs the QT interval. [28221] [28432] [28457] [41806] [65157] [65170] Dolasetron: (Major) Avoid coadministration of dolasetron and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. [41806] [42844] [65157] [65170] Dolutegravir; Rilpivirine: (Major) Avoid coadministration of rilpivirine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. [41806] [44376] [65157] [65170] Donepezil: (Major) Avoid coadministration of donepezil and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. [41806] [59321] [59322] [65157] [65170] Donepezil; Memantine: (Major) Avoid coadministration of donepezil and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. [41806] [59321] [59322] [65157] [65170] Dronedarone: (Contraindicated) Avoid concomitant use of hydroxychloroquine and dronedarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [36101] [41806] Droperidol: (Major) Avoid coadministration of droperidol and hydroxychloroquine due to the risk of increased QT prolongation.If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Hydroxychloroquine prolongs the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). [28235] [28236] [28737] [41806] [51289] [65157] [65170] Dulaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Edoxaban: (Moderate) Use caution if hydroxychloroquine is coadministered with edoxaban due to the potential for increased edoxaban exposure which may increase the risk of bleeding. Edoxaban is a P-gp substrate; limited data suggests that hydroxychloroquine is a P-gp inhibitor. [58685] [65210] Efavirenz: (Major) Avoid coadministration of efavirenz and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. QTc prolongation has been observed with the use of efavirenz. [28442] [41806] [65157] [65170] Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of efavirenz and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. QTc prolongation has been observed with the use of efavirenz. [28442] [41806] [65157] [65170] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of efavirenz and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. QTc prolongation has been observed with the use of efavirenz. [28442] [41806] [65157] [65170] Eliglustat: (Major) Avoid coadministration of eliglustat and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. [41806] [57803] [65157] [65170] Empagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Avoid coadministration of rilpivirine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. [41806] [44376] [65157] [65170] Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of rilpivirine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. [41806] [44376] [65157] [65170] Encorafenib: (Major) Avoid coadministration of encorafenib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Encorafenib is associated with dose-dependent prolongation of the QT interval. [41806] [63317] [65157] [65170] Entrectinib: (Major) Avoid coadministration of entrectinib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Entrectinib has also been associated with QT prolongation. [41806] [64567] [65157] [65170] Eribulin: (Major) Avoid coadministration of eribulin and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both hydroxychloroquine and eribulin have been associated with QT prolongation. [41806] [42449] [65157] [65170] Ertugliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Erythromycin: (Major) Concomitant use of hydroxychloroquine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28251] [41806] [65170] Escitalopram: (Major) Concomitant use of hydroxychloroquine and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28270] [41806] [65170] Eslicarbazepine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as eslicarbazepine. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Ethosuximide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as ethosuximide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Ethotoin: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as ethotoin. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Exenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Felbamate: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as felbamate. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Fingolimod: (Major) Avoid coadministration of fingolimod and hydroxychloroquine due to the risk of increased QT prolongation. If coadministration cannot be avoided, overnight monitoring with continuous ECG in a medical facility is advised after the first fingolimod dose for patients taking QT prolonging drugs with a known risk of torsade de pointes (TdP). Also, avoid any non-essential QT prolonging drugs and correct electrolyte imbalances. Monitor ECG throughout therapy. Hydroxychloroquine prolongs the QT interval. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. [41806] [41823] [65157] [65170] Flecainide: (Major) Concomitant use of hydroxychloroquine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [23774] [28752] [41806] [65170] Fluconazole: (Major) Concomitant use of hydroxychloroquine and fluconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28674] [41806] [65170] Fluoxetine: (Major) Concomitant use of hydroxychloroquine and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [32127] [41806] [44058] [65170] Fluphenazine: (Major) Avoid coadministration of fluphenazine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Fluphenazine is associated with a possible risk for QT prolongation. [28514] [41806] [65157] [65170] Fluvoxamine: (Major) Avoid coadministration of fluvoxamine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Cases of QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of fluvoxamine. [41806] [50507] [65157] [65170] Foscarnet: (Major) Avoid coadministration of foscarnet and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). [28377] [41806] [65157] [65170] Fosphenytoin: (Moderate) Monitor for a decrease in hydroxychloroquine and fosphenytoin efficacy if coadministration is necessary. Antiepileptic drug activity may be impaired if coadministered with hydroxychloroquine and concomitant use may decrease exposure of hydroxychloroquine. Hydroxychloroquine is a CYP3A substrate and fosphenytoin is a strong CYP3A inducer. [28535] [41806] [56579] [65210] [65239] Fostemsavir: (Major) Avoid coadministration of hydroxychloroquine and fostemsavir due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation. [41806] [65157] [65170] [65666] Gabapentin: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant gabapentin and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Gemifloxacin: (Major) Avoid coadministration of gemifloxacin and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. [28424] [28432] [28457] [29833] [33144] [33145] [33146] [41806] [48869] [49971] [65157] [65170] Gemtuzumab Ozogamicin: (Major) Avoid coadministration of gemtuzumab and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. [41806] [62292] [65157] [65170] Gilteritinib: (Major) Avoid coadministration of gilteritinib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both drugs have been associated with QT prolongation. [41806] [63787] [65157] [65170] Glasdegib: (Major) Avoid coadministration of glasdegib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. [41806] [63777] [65157] [65170] Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Glimepiride; Rosiglitazone: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Glipizide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Glyburide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Goserelin: (Major) Avoid coadministration of goserelin and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Androgen deprivation therapy (e.g., goserelin) also may prolong the QT/QTc interval. [28592] [41806] [65157] [65170] Granisetron: (Major) Avoid coadministration of granisetron and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both drugs have been associated with QT prolongation. [31723] [41806] [65157] [65170] Halogenated Anesthetics: (Major) Avoid coadministration of halogenated anesthetics and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both hydroxychloroquine and halogenated anesthetics can prolong the QT interval. [28457] [28458] [28754] [28755] [28756] [41806] [65157] [65170] Haloperidol: (Major) Avoid coadministration of haloperidol and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. [23500] [23779] [28225] [28307] [28415] [28416] [41806] [65157] [65170] Histrelin: (Major) Avoid coadministration of histrelin and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Androgen deprivation therapy (e.g., histrelin) also may prolong the QT/QTc interval. [30369] [41806] [65157] [65170] Hydroxyzine: (Major) Concomitant use of hydroxychloroquine and hydroxyzine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [47129] [65170] Ibutilide: (Major) Concomitant use of ibutilide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [41830] [65157] [65170] Iloperidone: (Major) Concomitant use of iloperidone and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [36146] [41806] [65157] [65170] Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Inotuzumab Ozogamicin: (Major) Concomitant use of inotuzumab and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [62245] [65157] [65170] Insulin Aspart: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Insulin Degludec: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Insulin Detemir: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Insulin Glargine: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Insulin Lispro: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Insulins: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Isoflurane: (Major) Avoid coadministration of halogenated anesthetics and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both hydroxychloroquine and halogenated anesthetics can prolong the QT interval. [28457] [28458] [28754] [28755] [28756] [41806] [65157] [65170] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid concomitant use of hydroxychloroquine and rifampin as lack of efficacy of hydroxychloroquine was reported when administered together. Coadministration may decrease the exposure of hydroxychloroquine. Hydroxychloroquine may be a CYP3A4 substrate in vitro, and rifampin is a strong CYP3A4 inducer. [41806] [65210] Isoniazid, INH; Rifampin: (Major) Avoid concomitant use of hydroxychloroquine and rifampin as lack of efficacy of hydroxychloroquine was reported when administered together. Coadministration may decrease the exposure of hydroxychloroquine. Hydroxychloroquine may be a CYP3A4 substrate in vitro, and rifampin is a strong CYP3A4 inducer. [41806] [65210] Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Itraconazole: (Major) Avoid coadministration of itraconazole and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine and itraconazole have been associated with prolongation of the QT interval. [40233] [41806] [57441] [65157] [65170] Ivosidenib: (Major) Avoid coadministration of ivosidenib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Dose reduce or interrupt ivosidenib therapy if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Hydroxychloroquine also prolongs the QT interval. [41806] [63368] [65157] [65170] Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and hydroxychloroquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [27982] [41806] [65170] [67231] Lacosamide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as lacosamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Lamotrigine: (Moderate) Monitor for seizures during concomitant use of hydroxychloroquine and lamotrigine. Hydroxychloroquine can lower the seizure threshold and the activity of antiepileptics may be impaired during concomitant use. [41806] Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). [28225] [28238] [41806] [65157] [65170] Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like hydroxychloroquine, may interact with lanthanum carbonate. Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and lanthanum carbonate at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [44406] [61758] Lapatinib: (Major) Avoid coadministration of lapatinib and hydroxychloroquine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Lapatinib has also been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. [33192] [41806] [65157] [65170] Lefamulin: (Major) Avoid coadministration of lefamulin and hydroxychloroquine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. [41806] [64576] [65157] [65170] Lente Insulin: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Lenvatinib: (Major) Concomitant use of lenvatinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [58782] [65157] [65170] Leuprolide: (Major) Concomitant use of leuprolide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [43800] [65157] [65170] Leuprolide; Norethindrone: (Major) Concomitant use of leuprolide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [43800] [65157] [65170] Levetiracetam: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant levetiracetam and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Levofloxacin: (Major) Concomitant use of hydroxychloroquine and levofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28421] [41806] [65170] Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and hydroxychloroquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [27982] [41806] [65170] [67231] Linagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Lithium: (Major) Concomitant use of hydroxychloroquine and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [59809] [59810] [59811] [65170] Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Lofexidine: (Major) Concomitant use of lofexidine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [63161] [65157] [65170] Loperamide: (Major) Concomitant use of hydroxychloroquine and loperamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [30106] [41806] [60864] [65170] Loperamide; Simethicone: (Major) Concomitant use of hydroxychloroquine and loperamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [30106] [41806] [60864] [65170] Lopinavir; Ritonavir: (Major) Concomitant use of lopinavir and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28341] [41806] [65157] [65170] Lorazepam: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant lorazepam and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Macimorelin: (Major) Avoid coadministration of macimorelin and hydroxychloroquine due to an increased risk of QT prolongation and torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Hydroxychloroquine prolongs the QT interval. [41806] [62723] [65157] [65170] Maprotiline: (Major) Avoid coadministration of maprotiline and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. [28225] [28759] [41806] [65157] [65170] Mefloquine: (Major) Avoid coadministration of hydroxychloroquine with mefloquine due to an increased risk of QT prolongation and seizures. These drugs are both analogs of quinine. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Also, both drugs may lower the seizure threshold. [28301] [41806] [65157] [65170] Meglitinides: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the meglitinides, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent. [41806] Meperidine; Promethazine: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [55578] [65170] Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Metformin; Repaglinide: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the meglitinides, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent. [41806] (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Metformin; Rosiglitazone: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Methadone: (Major) Avoid coadministration of methadone and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Methadone is considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (more than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. [28319] [28320] [28321] [28322] [33136] [41806] [65157] [65170] Methotrexate: (Moderate) Monitor for increased methotrexate-related adverse reactions during concomitant hydroxychloroquine use. Concomitant use may increase the risk for methotrexate toxicity. [31335] [41806] [56263] Methsuximide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as methsuximide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Metronidazole: (Major) Concomitant use of metronidazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [36894] [41806] [65170] Midostaurin: (Major) Avoid coadministration of midostaurin and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. In clinical trials, QT prolongation has been reported in patients who received midostaurin. [41806] [61906] [65157] [65170] Mifepristone: (Major) Concomitant use of hydroxychloroquine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [48697] [65170] Miglitol: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the alpha-glucosidase inhibitors, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent. [41806] Mirtazapine: (Major) Concomitant use of hydroxychloroquine and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [40942] [41806] [65170] Mobocertinib: (Major) Concomitant use of mobocertinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [65170] [66990] Moxifloxacin: (Major) Avoid coadministration of moxifloxacin and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. [28423] [28432] [28457] [29833] [33144] [33145] [33146] [41806] [48869] [48871] [65157] [65170] Nateglinide: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the meglitinides, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent. [41806] Nilotinib: (Major) Avoid coadministration of nilotinib and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. [41806] [58766] [65157] [65170] Octreotide: (Major) Avoid coadministration of octreotide and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. [28432] [29113] [30624] [41806] [65157] [65170] Ofloxacin: (Major) Concomitant use of hydroxychloroquine and ofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [29833] [30738] [41806] [48869] [65170] Olanzapine: (Major) Avoid coadministration of olanzapine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. [28785] [32732] [32734] [32745] [32746] [41806] [65157] [65170] Olanzapine; Fluoxetine: (Major) Avoid coadministration of olanzapine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. [28785] [32732] [32734] [32745] [32746] [41806] [65157] [65170] (Major) Concomitant use of hydroxychloroquine and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [32127] [41806] [44058] [65170] Olanzapine; Samidorphan: (Major) Avoid coadministration of olanzapine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. [28785] [32732] [32734] [32745] [32746] [41806] [65157] [65170] Omeprazole; Sodium Bicarbonate: (Major) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [61758] Ondansetron: (Major) Concomitant use of hydroxychloroquine and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose. [31266] [41806] [65170] Osilodrostat: (Major) Avoid coadministration of osilodrostat and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Osilodrostat is associated with dose-dependent QT prolongation. [41806] [65098] [65157] [65170] Osimertinib: (Major) Avoid coadministration of osimertinib and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Hydroxychloroquine prolongs the QT interval. [41806] [60297] [65157] [65170] Oxaliplatin: (Major) Avoid coadministration of oxaliplatin and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Hydroxychloroquine prolongs the QT interval. [41806] [41958] [65157] [65170] Ozanimod: (Major) Avoid coadministration of hydroxychloroquine and ozanimod due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia. [41806] [65157] [65169] [65170] Pacritinib: (Major) Concomitant use of pacritinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [65170] [67427] Paliperidone: (Major) Avoid coadministration of paliperidone and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Paliperidone has been associated with QT prolongation; Torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. [40936] [41806] [65157] [65170] Panobinostat: (Major) Avoid coadministration of panobinostat and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. QT prolongation has also been reported with panobinostat. [41806] [58821] [65157] [65170] Pasireotide: (Major) Avoid coadministration of pasireotide and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. [41806] [52611] [65157] [65170] Pazopanib: (Major) Avoid coadministration of pazopanib and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine and pazopanib both prolong the QT interval. [37098] [41806] [65157] [65170] Penicillamine: (Major) Do not use penicillamine concurrently with antimalarials due to an increased risk of severe hematologic and renal adverse reactions. [28834] Pentamidine: (Major) Avoid coadministration of pentamidine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Systemic pentamidine has been associated with QT prolongation. [23620] [23778] [28419] [28879] [41806] [65157] [65170] Pentobarbital: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as pentobarbital. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Perampanel: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as perampanel. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Perphenazine: (Major) Avoid coadministration of perphenazine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Perphenazine is associated with a possible risk for QT prolongation. [28514] [41806] [65157] [65170] Perphenazine; Amitriptyline: (Major) Avoid coadministration of perphenazine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Perphenazine is associated with a possible risk for QT prolongation. [28514] [41806] [65157] [65170] Phenobarbital: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as phenobarbital. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. Additionally, coadministration of phenobarbital may decrease exposure of hydroxychloroquine resulting in decreased efficacy. [41806] [65210] Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as phenobarbital. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. Additionally, coadministration of phenobarbital may decrease exposure of hydroxychloroquine resulting in decreased efficacy. [41806] [65210] Phentermine; Topiramate: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant topiramate and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Phenytoin: (Moderate) Monitor for a decrease in hydroxychloroquine and phenytoin efficacy if coadministration is necessary. Antiepileptic drug activity may be impaired if coadministered with hydroxychloroquine and concomitant use may decrease exposure of hydroxychloroquine. Hydroxychloroquine is a CYP3A substrate and phenytoin is a strong CYP3A inducer. [41806] [46974] [65210] [65239] Pimavanserin: (Major) Avoid coadministration of pimavanserin and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine and pimavanserin both prolong the QT interval. [41806] [60748] [65157] [65170] Pimozide: (Contraindicated) Avoid concomitant use of pimozide and hydroxychloroquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [28225] [41806] [43463] Pioglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Pioglitazone; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Pitolisant: (Major) Avoid coadministration of pitolisant and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both pitolisant and hydroxychloroquine prolong the QT interval. [41806] [64562] [65157] [65170] Ponesimod: (Major) Avoid coadministration of hydroxychloroquine and ponesimod due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia. [41806] [65170] [66527] Posaconazole: (Major) Avoid coadministration of posaconazole and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. [32723] [41806] [65157] [65170] Pramlintide: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including pramlintide, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent. [41806] Praziquantel: (Minor) Hydroxychloroquine may reduce praziquantel bioavailability and maximum serum concentrations as was observed with the structurally similar chloroquine. The mechanism of the interaction is not certain. Clinicians should be alert to the possibility of praziquantel failure if hydroxychloroquine is used. [27846] [41806] Pregabalin: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant pregabalin and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Primaquine: (Major) Avoid coadministration of primaquine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Primaquine is associated with the potential for QT prolongation. [41806] [41984] [65157] [65170] Primidone: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as primidone. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Procainamide: (Major) Avoid coadministration of procainamide and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). [28250] [41806] [65157] [65170] Prochlorperazine: (Major) Avoid coadministration of prochlorperazine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. [28514] [41806] [65157] [65170] Promethazine: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [55578] [65170] Promethazine; Dextromethorphan: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [55578] [65170] Promethazine; Phenylephrine: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [55578] [65170] Propafenone: (Major) Concomitant use of hydroxychloroquine and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28287] [41806] [65170] Quetiapine: (Major) Concomitant use of hydroxychloroquine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [29118] [41806] [65170] Quinidine: (Major) Avoid coadministration of quinidine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). [41806] [42280] [47357] [65157] [65170] Quinine: (Major) Avoid coadministration of quinine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). [31403] [41806] [65157] [65170] Rabies Vaccine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced. [40848] [40849] Ranolazine: (Major) Avoid coadministration of ranolazine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. [31938] [41806] [65157] [65170] Regular Insulin: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Relugolix: (Major) Avoid coadministration of hydroxychloroquine and relugolix due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. [41806] [65157] [65170] [66183] Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of hydroxychloroquine and relugolix due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. [41806] [65157] [65170] [66183] Remdesivir: (Major) Coadministration of remdesivir and hydroxychloroquine is not recommended. Based on data from cell culture experiments, the intracellular metabolic activation and antiviral activity of remdesivir may be antagonized by chloroquine phosphate in a dose-dependent manner. [65365] [66063] Repaglinide: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the meglitinides, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent. [41806] Ribociclib: (Major) Avoid coadministration of ribociclib and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. [41806] [61816] [65157] [65170] Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. [41806] [61816] [65157] [65170] Rifampin: (Major) Avoid concomitant use of hydroxychloroquine and rifampin as lack of efficacy of hydroxychloroquine was reported when administered together. Coadministration may decrease the exposure of hydroxychloroquine. Hydroxychloroquine may be a CYP3A4 substrate in vitro, and rifampin is a strong CYP3A4 inducer. [41806] [65210] Rilpivirine: (Major) Avoid coadministration of rilpivirine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. [41806] [44376] [65157] [65170] Risperidone: (Major) Avoid coadministration of risperidone and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de points (TdP), primarily in the overdose setting. [22256] [28225] [28414] [28416] [41806] [65157] [65170] Rituximab: (Moderate) The concomitant use of rituximab with other disease modifying anti-rheumatic drugs (DMARDs), such as hydroxychloroquine, may result in an increased risk of infection. Hydroxychloroquine itself does not increase immunosuppression or infection risk, but, is often used in DMARD regimens where infection risk is increased. Monitor patients closely for signs or symptoms of infection. [41806] [49773] [56233] Rituximab; Hyaluronidase: (Moderate) The concomitant use of rituximab with other disease modifying anti-rheumatic drugs (DMARDs), such as hydroxychloroquine, may result in an increased risk of infection. Hydroxychloroquine itself does not increase immunosuppression or infection risk, but, is often used in DMARD regimens where infection risk is increased. Monitor patients closely for signs or symptoms of infection. [41806] [49773] [56233] Romidepsin: (Major) Avoid coadministration of romidepsin and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Romidepsin has been reported to prolong the QT interval. [37292] [41806] [65157] [65170] Rosiglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Rufinamide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as rufinamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Saquinavir: (Major) Avoid coadministration of saquinavir and hydroxychloroquine due to an increased risk of QT prolongation. If no acceptable alternative therapy is available, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Hydroxychloroquine prolongs the QT interval. [28995] [41806] [65157] [65170] Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Selpercatinib: (Major) Avoid coadministration of hydroxychloroquine and selpercatinib due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. [41806] [65157] [65170] [65387] Semaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Sertraline: (Major) Concomitant use of hydroxychloroquine and sertraline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose. [28343] [41806] [65170] Sevoflurane: (Major) Avoid coadministration of halogenated anesthetics and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both hydroxychloroquine and halogenated anesthetics can prolong the QT interval. [28457] [28458] [28754] [28755] [28756] [41806] [65157] [65170] SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Simvastatin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Siponimod: (Major) Avoid coadministration of siponimod and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Hydroxychloroquine prolongs the QT interval. [41806] [64031] [65157] [65170] Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Sodium Bicarbonate: (Major) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495). [30284] [30285] [41806] [61758] Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [64608] [65170] Solifenacin: (Major) Avoid coadministration of solifenacin and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. [30515] [41806] [65157] [65170] Sorafenib: (Major) Avoid coadministration of hydroxychloroquine and sorafenib due to the risk of increased QT prolongation. If concomitant use is unavoidable, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Sorafenib is also associated with QTc prolongation. [31832] [41806] [65157] [65170] Sotalol: (Major) Concomitant use of hydroxychloroquine and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28234] [41806] [65170] Sulfonylureas: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Sunitinib: (Major) Avoid coadministration of sunitinib and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine and sunitinib can prolong the QT interval. [31970] [41806] [65157] [65170] Tacrolimus: (Major) Avoid coadministration of tacrolimus and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). [27954] [28611] [41806] [65157] [65170] Tamoxifen: (Major) Concomitant use of tamoxifen and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the risk of retinal toxicity. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [61871] [61872] [63589] [65157] [65170] Telavancin: (Major) Concomitant use of telavancin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [36615] [41806] Telbivudine: (Minor) Monitor patients for signs or symptoms of unexplained muscle pain, tenderness, or weakness during concomitant treatment with hydroxychloroquine and telbivudine. Interrupt telbivudine therapy if myopathy is suspected and discontinue telbivudine if myopathy is confirmed. It is unknown if the risk of myopathy during treatment with telbivudine is increased with coadministration of other drugs associated with myopathy, like hydroxychloroquine. [32827] Telithromycin: (Major) Concomitant use of telithromycin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28156] [41806] [65157] [65170] Tetrabenazine: (Major) Concomitant use of tetrabenazine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [34389] [41806] [65157] [65170] Thiazolidinediones: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Thioridazine: (Contraindicated) Avoid concomitant use of thioridazine and hydroxychloroquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. [28225] [28293] [41806] Tiagabine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as tiagabine. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Tirzepatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Tolazamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Tolbutamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Tolterodine: (Major) Concomitant use of tolterodine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The risk for tolterodine-associated QT/QTc prolongation may be increased in poor CYP2D6 metabolizers. [31112] [41806] [65157] [65170] Topiramate: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant topiramate and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Toremifene: (Major) Concomitant use of toremifene and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28822] [41806] [65157] [65170] Trazodone: (Major) Concomitant use of hydroxychloroquine and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [38831] [41806] [65170] Triclabendazole: (Major) Concomitant use of triclabendazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [63962] [65170] Trifluoperazine: (Major) Concomitant use of trifluoperazine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [65157] [65170] Triptorelin: (Major) Concomitant use of triptorelin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [45411] [65157] [65170] Ultralente Insulin: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. [41806] Valproic Acid, Divalproex Sodium: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as valproic acid. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Vandetanib: (Major) Concomitant use of vandetanib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [43901] [65157] [65170] Vardenafil: (Major) Concomitant use of hydroxychloroquine and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28216] [41806] [65170] Vemurafenib: (Major) Concomitant use of vemurafenib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [41806] [45335] [65157] [65170] Venlafaxine: (Major) Concomitant use of hydroxychloroquine and venlafaxine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [33715] [41806] [65170] Vigabatrin: (Major) Vigabatrin should not be used with hydroxychloroquine, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks. Additionally, hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [36250] [41806] Voclosporin: (Major) Concomitant use of voclosporin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose. [41806] [65157] [65170] [66336] Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). [28225] [28238] [41806] [65157] [65170] Voriconazole: (Major) Avoid coadministration of voriconazole and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). [28158] [41806] [65157] [65170] Vorinostat: (Major) Concomitant use of vorinostat and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [32789] [41806] [65157] [65170] Ziprasidone: (Major) Concomitant use of ziprasidone and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. [28233] [41806] [65157] [65170] Zonisamide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as zonisamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806]
Revision Date: 11/29/2022, 02:30:00 AM

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Monitoring Parameters

  • blood glucose
  • CBC
  • ECG
  • glucose-6-phosphate dehydrogenase (G6PD) activity
  • ophthalmologic exam

US Drug Names

  • Plaquenil
  • Quineprox
;