English

ThisiscontentfromElsevier'sDrugInformation

Ticagrelor

Learn more about Elsevier's Drug Information today! Get the drug data and decision support you need, including TRUE Daily Updates™ including every day including weekends and holidays.

May.22.2023

Ticagrelor

Indications/Dosage

Labeled

  • acute myocardial infarction
  • arterial thromboembolism prophylaxis
  • coronary artery disease
  • myocardial infarction prophylaxis
  • percutaneous coronary intervention (PCI)
  • stroke prophylaxis
  • unstable angina

General dosing information

Switching from another P2Y12 inhibitor to ticagrelor:

  • Switching from intravenous cangrelor:
    • Administer ticagrelor 180 mg PO loading dose at any time during cangrelor infusion or immediately after infusion discontinuation, then ticagrelor 90 mg PO twice daily.[59845][68765][68768]
  • Switching from clopidogrel:
    • Within 30 days of the index event: Discontinue clopidogrel and administer ticagrelor 180 mg PO loading dose irrespective of the timing of the last clopidogrel dose, then ticagrelor 90 mg PO twice daily starting 24 hours after the last clopidogrel dose.
    • More than 30 days of the index event: Discontinue clopidogrel and administer ticagrelor 90 mg PO twice daily 24 hours after the last clopidogrel dose.[68765][68766][68767][68768][68769][68774]
  • Switching from prasugrel:
    • Within 30 days of the index event: Discontinue prasugrel and administer ticagrelor 180 mg PO loading dose 24 hours after the last prasugrel dose, then administer ticagrelor 90 mg PO twice daily
    • More than 30 days from the index event: Discontinue prasugrel and administer ticagrelor 90mg PO twice daily starting 24 hours after the last prasugrel dose.[68765][68766][68767][68768][68769][68774]

Switching from ticagrelor to another P2Y12 inhibitor:

  • Bridging to intravenous cangrelor:
    • Discontinue ticagrelor and initiate cangrelor 0.75 mcg/kg/minute (without a bolus dose) 2 to 3 days after the last administered ticagrelor dose. Consider platelet function testing to determine time to initiate cangrelor infusion.[59845][68765][68768][68772]
  • Switching to clopidogrel:
    • Within 30 days of index event and without bleeding or bleeding concerns: Discontinue ticagrelor and administer clopidogrel 600 mg PO loading dose 12 to 24 hours after the last ticagrelor dose, then clopidogrel 75 mg PO once daily.
    • Within 30 days of index event and with bleeding or bleeding concerns: Discontinue ticagrelor and consider switching directly to clopidogrel maintenance dose of 75 mg PO once daily 12 to 24 hours after the last ticagrelor dose.
    • More than 30 days from the index event and without bleeding or bleeding concerns: Discontinue ticagrelor and administer clopidogrel 600 mg PO loading dose 12 to 24 hours after the last ticagrelor dose, then clopidogrel 75 mg PO once daily.
    • More than 30 days from the index event and with bleeding or bleeding concerns: Discontinue ticagrelor and consider switching directly to clopidogrel maintenance dose of 75 mg PO once daily 12 to 24 hours after the last ticagrelor dose.[68765][68766][68767][68768][68769][68774]
  • Switching to prasugrel:
    • Within 30 days of the index event: Discontinue ticagrelor and administer prasugrel 60 mg PO loading dose 24 hours after the last prasugrel dose, then prasugrel 10 mg PO once daily.
    • More than 30 days of the index event: Discontinue ticagrelor and administer prasugrel 60 mg PO loading dose 24 hours after the last ticagrelor dose, then prasugrel 10 mg PO once daily.[68765][68766][68767][68768][68769][68774]

Off-Label

    † Off-label indication

    For arterial thromboembolism prophylaxis in persons with acute coronary syndrome (ACS) (unstable angina, acute myocardial infarction), including those undergoing percutaneous coronary intervention (PCI)

    Oral dosage

    Adults

    180 mg PO loading dose, then 90 mg PO twice daily in combination with low-dose aspirin. Reduce dose to 60 mg PO twice daily in combination with low-dose aspirin after 1 year.[44951]

    For the reduction in risk of first myocardial infarction (myocardial infarction prophylaxis) or stroke in patients with coronary artery disease (CAD) at high risk for these events.

    Oral dosage

    Adults

    60 mg PO twice daily plus aspirin 75 mg to 100 mg PO once daily. Avoid maintenance doses of aspirin above 100 mg/day due to reduced efficacy of ticagrelor.[44951]

    For stroke prophylaxis in patients with acute ischemic stroke (NIH stroke scale score 5 or less) or high risk transient ischemic attack (TIA)

    Oral dosage

    Adults

    180 mg PO loading dose plus aspirin (300 mg to 325 mg PO), then 90 mg PO twice daily plus aspirin (75 to 100 mg PO once daily) for up to 30 days. Avoid maintenance doses of aspirin above 100 mg/day due to reduced efficacy of ticagrelor.[44951]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      180 mg/day PO after an initial 180 mg load for acute coronary syndrome; 120 mg/day PO for coronary artery disease.

    • Geriatric

      180 mg/day PO after an initial 180 mg load for acute coronary syndrome; 120 mg/day PO for coronary artery disease.

    • Adolescents

      Safety and efficacy have not been established.

    • Children

      Safety and efficacy have not been established.

    • Infants

      Safety and efficacy have not been established.

    • Neonates

      Safety and efficacy have not been established.

    Patients with Hepatic Impairment Dosing

    Mild hepatic impairment: No dose adjustment needed.

    Moderate hepatic impairment: Use with caution; carefully weigh the risks versus the benefits of treatment, considering the probable increase in exposure to ticagrelor.

    Severe hepatic impairment: Use is contraindicated.

    Patients with Renal Impairment Dosing

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    † Off-label indication
    Revision Date: 05/22/2023, 12:55:23 PM

    References

    44951 - Brilinta (ticagrelor) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 May.59845 - Kengreal (cangrelor) injection. Cary, NC: Chiesi USA, Inc.; 2023 Jan.68765 - Angiolillo DJ, Rollini F, Storey RF, et al. International expert consensus on switching Platelet P2Y12 receptor-inhibiting therapies. Circulation 2017;136:1955-1975.68766 - Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: the task force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2018;39(3):213-260.68767 - Caprazano P, Francaviglia B, Angiolillo D. Pharmacodynamics during transition between platelet P2Y12 inhibiting therapies. Intervent Cardiol Clin 2019;8:321-340.68768 - American College of Cardiology. Infographic: Medication safety: switching P2Y12 inhibitors. Accessed March 23, 2023. Available on the World Wide Web at https://www.acc.org/education-and-meetings/image-and-slide-gallery/media-detail?id=d6590efa65fd4881ad53196eb1e618a168769 - Gasecka A, Konwerski M, Pordzik J, et al. Switching between P2Y12 antagonists: from bench to bedside. Vascul Pharmacol 2019;115:1-12.68772 - Angiolillo DJ, Firstenberg MS, Price MJ, et al. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA 2012;307:265-274.68774 - De Luca L, Capranzano P, Patti G, et al. Switching of platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: review of the literature and practical considerations. Am Heart J 2016;176:44-52.

    How Supplied

    Ticagrelor Oral tablet

    BRILINTA 60mg Tablet (00186-0776) (AstraZeneca LP) null

    Ticagrelor Oral tablet

    BRILINTA 90mg 7-Day Pack Tablet (00186-0777) (AstraZeneca LP) (off market)

    Ticagrelor Oral tablet

    BRILINTA 90mg Tablet (00186-0777) (AstraZeneca LP) null

    Description/Classification

    Description

    Ticagrelor is an oral platelet P2Y12 adenosine-5'-diphosphate (ADP) receptor antagonist that inhibits platelet aggregation. Ticagrelor is indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS) (unstable angina, non-ST elevation myocardial infarction, or ST-elevation myocardial infarction); to reduce the risk of first myocardial infarction or stroke in patients with coronary artery disease at high risk for these events, such as patients with type 2 diabetes; and to reduce the risk of stroke in patients with acute ischemic stroke (NIH stroke scale score 5 or less) or high-risk transient ischemic attack (TIA). In the PLATO study, ticagrelor was shown to reduce the rate of a combined endpoint of cardiovascular death, myocardial infarction, or stroke compared to clopidogrel in patients with ACS.[44951] The efficacy and safety of ticagrelor and clopidogrel were found to be similar in a meta-analysis of ACS clinical studies; however, ticagrelor had a higher incidence of dyspnea.[66096] In the THEMIS study that compared the safety and efficacy of ticagrelor plus aspirin versus placebo plus aspirin in patients with stable coronary artery disease and type 2 diabetes mellitus, the incidence of the composite primary efficacy outcome of cardiovascular death, myocardial infarction, or stroke was lower in the ticagrelor plus aspirin group (7%) than in the placebo plus aspirin group (8.5%) (hazard ratio 0.9; 95% CI, 0.81 to 0.99; p = 0.04). The incidence of major bleeding and intracranial bleeding was higher in the ticagrelor group at 2.2% and 0.7%, respectively, compared to 1% and 0.5%, respectively, in the placebo group.[66098] The THALES study enrolled patients with mild to moderate acute noncardioembolic ischemic stroke (NIH stroke scales score 5 or less) or transient ischemic attack to compare the effect of ticagrelor plus aspirin to aspirin on the prevention of stroke or death. Dual therapy with ticagrelor plus aspirin was associated with a reduced risk of the composite end point of stroke and death (5.4%) compared to aspirin (6.5%) (p = 0.02), but there was no difference in the incidence of disability (23.8% versus 24.1%). The incidence of ischemic stroke was also lower with ticagrelor plus aspirin versus aspirin, 5% and 6.2%, respectively (p = 0.004). The incidence of severe bleeding was higher in the ticagrelor plus aspirin group compared to the aspirin group, 0.5% versus 0.1% (p = 0.001).[66099] Ticagrelor has also been found to reduce the risk of stent thrombosis in patients with stents for ACS.[44951] Unlike clopidogrel, ticagrelor does not require hepatic activation to an active form and does not have irreversible effects on platelets.

    Classifications

    • Blood and Blood Forming Organs
      • Antithrombotic Agents
        • Platelet Aggregation Inhibitors
          • ADP (adenosine Diphosphate) Receptor Antagonist Platelet Aggregation Inhibitors
    Revision Date: 08/13/2021, 03:57:34 PM

    References

    44951 - Brilinta (ticagrelor) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 May.66096 - Wang D, Yang XH, Zhang J, et al. Compared efficacy of clopidogrel and ticagrelor in treating acute coronary syndrome: a meta-analysis. BMC Cardiovascular Disorders. 2018;18:217.66098 - Steg PG, Bhatt DL, Simon T, et al. Ticagrelor in patients with stable coronary disease and diabetes. N Engl J Med. 2019;381:1309-1320.66099 - Johnston SC, Amarenco P, Denison H, et al. Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA. N Engl J Med. 2020;383:207-217.

    Administration Information

    General Administration Information

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

    Route-Specific Administration

    Oral Administration

    • May be administered with or without food.
    • If a patient misses a dose, they should take their next dose at its scheduled time.
    • For patients unable to swallow whole tablets, crush the tablets, mix with water and drink immediately. Refill the glass with water, stir, and drink contents immediately. Alternatively, the mixture may be administered via nasogastric tube (CH8 or greater). The nasogastric tube must be flushed with water after administration of the mixture.[44951]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
      Revision Date: 03/30/2015, 08:11:01 AM

      References

      44951 - Brilinta (ticagrelor) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 May.

      Adverse Reactions

      Moderate

      • bleeding
      • chest pain (unspecified)
      • dyspnea
      • hypertension
      • hyperuricemia
      • hypotension

      Severe

      • angioedema
      • apnea
      • atrial fibrillation
      • AV block
      • bradycardia
      • Cheyne-Stokes respiration
      • intracranial bleeding
      • thrombotic thrombocytopenic purpura (TTP)

      Mild

      • back pain
      • cough
      • diarrhea
      • dizziness
      • fatigue
      • gynecomastia
      • headache
      • nausea
      • rash
      • syncope

      Ticagrelor increases the risk of bleeding and can cause significant, sometimes fatal bleeding. In the PLATO trial, major bleeding events occurred mostly early, at the time of angiography, PCI, CABG, and other procedures, but the risk does persist during later use of antiplatelet therapy. Patients receiving ticagrelor plus aspirin had a greater risk of non-CABG major and minor bleeding compared to patients receiving clopidogrel plus aspirin (7.7% vs. 6.2%, respectively). Additionally, rates of major bleeding were 3.9% for ticagrelor vs. 3.3% for clopidogrel; fatal bleeding occurred in 0.2% of patients in both groups, and intracranial bleeding occurred in 0.3% of patients receiving ticagrelor vs. 0.2% of patients receiving clopidogrel. It should be noted that no baseline demographic factor altered the relative risk of bleeding with ticagrelor compared to clopidogrel. In addition, the rates of total major bleeds in patients who underwent CABG surgery were very high and similar between patients receiving ticagrelor plus aspirin (81.3%) and patients receiving clopidogrel plus aspirin (81.8%). Fatal and life-threatening bleeding rates in patients receiving ticagrelor who underwent CABG surgery were not increased. Bleeding caused permanent discontinuation of study drug in 2.3% of ticagrelor patients and 1% of clopidogrel patients. In the THEMIS study, there were 9 TIMI major bleeding events per 1,000 patient-years with ticagrelor compared to 4 events per 1,000 patient-years in patients receiving placebo. The rate of TIMI major or minor bleeding events, or those requiring medical attention was 46 events per 1,000 patient-years with ticagrelor compared to 18 events per 1,000 patient-years with placebo. In the THALES study, intracranial bleeding occurred in 21 ticagrelor patients and 6 placebo patients. Eleven patients receiving ticagrelor therapy and 2 receiving placebo experienced fatal bleeding events; majority were intracranial bleeding. In order to decrease the risk of bleeding, discontinue ticagrelor 5 days prior to surgery. Bleeding should be suspected in any patient who is hypotensive and has recently undergone coronary angiography, PCI, CABG, or other surgical procedures, even if the patient does not have any signs of bleeding. If possible, manage any bleeding episode without discontinuing ticagrelor as stopping the drug increases the risk of subsequent cardiovascular events. Platelet transfusion did not reverse the antiplatelet effect of ticagrelor in healthy volunteers and is not likely to be of benefit in patients with bleeding.[44951]

      Dyspnea has been reported during ticagrelor treatment. If a patient develops worsening, prolonged, or newly reported dyspnea during ticagrelor therapy, exclude underlying diseases that may cause dyspnea and require treatment. There is no treatment for dyspnea caused by ticagrelor. If dyspnea is determined to be caused by ticagrelor, continue treatment without interruption if possible. Discontinuation or interruption of ticagrelor therapy will increase the risk of myocardial infarction, stent thrombosis, and death. If the dyspnea becomes intolerable and ticagrelor discontinuation is needed, consider starting another antiplatelet agent. During the PLATO trial, dyspnea was reported in 13.8% compared to 7.8% of those receiving clopidogrel. The reported dyspnea was usually mild to moderate in intensity and most often resolved with continued ticagrelor treatment. Dyspnea led to study discontinuation in 0.9% of patients receiving ticagrelor compared to 0.1% receiving clopidogrel. Dyspnea was reported in 14.2% and 21% of patients treated with ticagrelor in the PEGASUS and THEMIS trials, respectively, and led to drug discontinuation in 4.3% and 6.9%, respectively, of patients. Further analysis from PLATO indicates there were no adverse effects on pulmonary function (FEV1) after 1 month or at least 6 months of chronic treatment. Central sleep apnea and Cheyne-Stokes respiration have been reported with postmarketing use of ticagrelor. Recurrence or worsening of central sleep apnea or Cheyne-Stokes respiration has also been reported following ticagrelor rechallenge. If central sleep apnea is suspected, consider further clinical challenge.[44951] In addition, cough was reported in 4.9% of patients receiving ticagrelor in the PLATO trial compared to 4.6% of those receiving clopidogrel.[65498]

      Cardiovascular adverse events have been reported with ticagrelor therapy. During the PLATO trial, hypertension was reported in 3.8% of patients receiving ticagrelor (vs. 4% clopidogrel) and hypotension was reported in 3.2% of ticagrelor-treated patients (vs. 3.3% clopidogrel). Chest pain (unspecified) was reported in 3.1% of patients taking ticagrelor (vs. 3.5% clopidogrel) and non-cardiac chest pain was reported in 3.7% of patients treated with ticagrelor (vs. 3.3% clopidogrel). Atrial fibrillation occurred more often in patients receiving clopidogrel compared to ticagrelor (4.6% vs. 4.2%). During clinical studies, ticagrelor was associated with an increase in the occurrence of Holter-detected bradyarrhythmias (including ventricular pauses); PLATO excluded patients at risk for bradycardia and associated events (e.g., sick sinus syndrome, second or third degree AV block, bradycardia-related syncope not protected with a pacemaker). During the PLATO trial, syncope, pre-syncope, and loss of consciousness were reported in 1.7% of patients receiving ticagrelor compared to 1.5% in the clopidogrel group. Furthermore, in a substudy of approximately 3,000 patients in PLATO, 6% of patients receiving ticagrelor experienced ventricular pauses compared to 3.5% receiving clopidogrel in the acute phase. After 1 month, ventricular pauses were reported in 2.2% in the ticagrelor group and 1.6% in the clopidogrel group.[44951]

      Headache and dizziness have been reported with ticagrelor therapy. During the PLATO trial, headache was reported in 6.5% of patients receiving ticagrelor (vs. 5.8% clopidogrel), and dizziness was reported in 4.5% of those in the ticagrelor group (vs. 3.9% clopidogrel).[44591]

      Gastrointestinal effects have been reported with ticagrelor therapy. During the PLATO trial, nausea was reported in 4.3% of patients receiving ticagrelor (vs. 3.8% clopidogrel) and diarrhea was reported in 3.7% of patients in the ticagrelor group (vs. 3.3%).[44951]

      During the PLATO trial, fatigue was reported in 3.2% of patients receiving ticagrelor and clopidogrel. Back pain was reported in 3.6% of those receiving ticagrelor compared to 3.3% of those in the clopidogrel group.[44951]

      Gynecomastia was reported in 0.23% of men receiving ticagrelor during the PLATO trial compared to 0.05% of men receiving clopidogrel. Other sex-hormonal adverse reactions did not differ between treatment groups.[44951]

      Hyperuricemia was reported during the PLATO trial; however, reports of gout did not differ between treatment groups (0.6% for each group). Serum uric acid concentrations increased approximately 0.6 mg/dl above baseline for those receiving ticagrelor and increased 0.2 mg/dl for those receiving clopidogrel. Hyperuricemia normalized within 30 days of discontinuing treatment.[44951]

      Hypersensitivity reactions including angioedema and rash (unspecified) have been reported during post-marketing use of ticagrelor.[44951]

      Thrombotic thrombocytopenic purpura (TTP) has been reported rarely in patients receiving ticagrelor and may occur following a short exposure (less than 2 weeks). A 31-year old man developed TTP following 5 weeks of ticagrelor therapy, ticagrelor was discontinued and he experienced clinical TTP remission following steroid treatment and 5 plasma exchange treatments. An 87-year old man developed TTP following 2 months of ticagrelor therapy. Ticagrelor was temporarily held and intravenous immunoglobulin administered along with plasma exchange and other supportive therapies.  Ticagrelor was restarted 6 days later and the patient developed worsening TTP-related symptoms after 3 days of therapy; thus, ticagrelor was again discontinued. The patient subsequently passed away a few days after ticagrelor was stopped the second time. TTP is a serious condition that can be fatal and requires urgent treatment.[44951] [64708] [64709]

      Revision Date: 08/11/2021, 07:55:28 PM

      References

      44591 - Aljurf M, Al Qurashi F, Al Mohareb F, et al. High efficacy and low toxicity of APL induction with concurrent idarubicin/ATRA followed by a novel and simplified outpatient post-remission therapy using single doses of idarubicin and intermittent ATRA. Med Oncol. 2010;27(3):702-707.44951 - Brilinta (ticagrelor) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 May.64708 - Dogan A, Ozdemir B, Bal H, Et al. Ticagrelor-associated thrombotic trombocytopenic purpura. Anatol J cardiol 2017;17:73-74.64709 - Wang X, Zhang S, Li L, et al. Ticagrelor-induced thrombotic thrombocytopenic purpura: a case report and review of the literature. Medicine (Baltimore) 2018. Epub ahead of print, e11206. doi: 10.1097/MD.0000000000011206.65498 - Cheng JWM. Ticagrelor: oral reversible P2Y12 receptor antagonist for the management of acute coronary syndromes. Clin Ther 2012;34:1209-1220.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • bleeding
      • intracranial bleeding
      • abrupt discontinuation
      • aspirin coadministration
      • AV block
      • bradycardia
      • breast-feeding
      • coronary artery bypass graft surgery (CABG)
      • geriatric
      • GI bleeding
      • heparin-induced thrombocytopenia (HIT)
      • hepatic disease
      • labor
      • obstetric delivery
      • pregnancy
      • sick sinus syndrome
      • sleep apnea
      • stroke
      • surgery
      • syncope

      Ticagrelor is contraindicated in patients with hypersensitivity (e.g., angioedema) to ticagrelor or any component of the product. Hypersensitivity reactions including angioedema have been reported.[44951]

      Ticagrelor is contraindicated in any patient with active pathological bleeding including peptic ulcer (GI bleeding) or intracranial bleeding. Patients with acute ischemic stroke or transient ischemic attacks (TIAs) and an NIH stroke scale score greater than 5, as well as, patients receiving thrombolysis were excluded from the THALES study; thus, ticagrelor is not recommended in these patients. Like other antiplatelet agents, ticagrelor can cause significant, sometimes fatal, bleeding. The risk of bleeding may be increased in older patients, patients with a history of bleeding disorders, performance of percutaneous invasive procedures, and concomitant use of medications that increase the risk of bleeding (e.g., anticoagulant and fibrinolytic therapy, higher doses of aspirin, and chronic nonsteroidal anti-inflammatory drugs [NSAIDS]). In order to decrease the risk of bleeding, discontinue ticagrelor at least 5 days prior to any surgery, particularly in those with a high risk of bleeding, when possible; ticagrelor may be resumed once hemostasis achieved. Do not start ticagrelor in patients planned to undergo urgent coronary artery bypass graft surgery (CABG). Bleeding should be suspected in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of ticagrelor. Since there is an increased risk of subsequent cardiovascular events associated with discontinuation of ticagrelor, if possible, manage bleeding without stopping ticagrelor. Platelet transfusion did not reverse the antiplatelet effect of ticagrelor in healthy volunteers and is not likely to be of benefit in patients with bleeding.[44951]

      Avoid the use of ticagrelor in patients with severe hepatic impairment because it is metabolized by the liver and impaired hepatic function can increase risks for bleeding and other adverse events. In addition, severe hepatic impairment increases the risk of bleeding because of reduced synthesis of coagulation proteins. Ticagrelor has not been studied in patients with moderate or severe hepatic disease or impairment. In patients with moderate hepatic impairment, consider the risks and benefits of treatment, noting the probable increase in exposure to ticagrelor. [44951]

      Available data from case-reports of ticagrelor use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. No adequate or well-controlled studies of ticagrelor in pregnant women exist. In animal reproduction studies, ticagrelor caused structural abnormalities at maternal doses about 5 to 7 times the maximum recommended human dose (MRHD) based on body surface area. Pup death and effects on pup growth were seen when ticagrelor was given at doses 10 times the MRHD to rats during late gestation and lactation. Ticagrelor should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.[44951] Furthermore, ticagrelor should be used with extreme caution near term and during labor and obstetric delivery because of the possibility of maternal postpartum hemorrhage.

      According to the manufacturer, it is unknown if ticagrelor or its metabolites are excreted into human breast milk. Since many drugs are excreted into human milk and due to the potentially serious adverse effects to the infant, the manufacturer states that breastfeeding is not recommended during ticagrelor therapy; thus, either ticagrelor therapy or breast-feeding should be discontinued.[44951] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.

      Avoid interruption or the abrupt discontinuation of ticagrelor therapy in patients being treated for coronary artery disease (CAD). Discontinuation of ticagrelor increases the risk of myocardial infarction, stent thrombosis, and death. If it is absolutely necessary to temporarily discontinue treatment (e.g., to treat bleeding or for elective surgery), restart therapy as soon as possible.[44951]

      Use ticagrelor with caution in patients with a history of sick sinus syndrome, second or third degree AV block, or syncope related to bradycardia and not protected by a pacemaker. Ticagrelor can cause ventricular pauses. Bradyarrhythmias, including AV block, have been reported with the postmarketing use of ticagrelor. Patients with sick sinus syndrome, AV block, or bradycardia-related syncope were excluded from ticagrelor clinical trials and may be at increased risk of developing bradyarrhythmias with ticagrelor.[44951]

      Ticagrelor is indicated for use with aspirin at doses of 75 to 100 mg per day. Avoid higher aspirin maintenance doses, as ticagrelor efficacy is decreased when aspirin coadministration exceeds 100 mg per day.[44951]

      No difference in safety or efficacy is seen between geriatric and younger patients. Approximately half of the patients in the PLATO, PEGASUS, THEMIS, and THALES trials were 65 years of age and older and at least 15% were 75 years of age and older. The relative risk of bleeding was similar in both age and treatment groups. Although no differences were seen in clinical trials, some older patients may be more sensitive to the effects of ticagrelor.[44951] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to the OBRA guidelines, platelet inhibitors may cause thrombocytopenia and increase the risk of bleeding. Common side effects of platelet inhibitors include headache, dizziness, and vomiting. Concurrent use with warfarin or NSAIDs may increase the risk of bleeding.[60742]

      Ticagrelor has been reported to cause false negative results in platelet function tests, including the heparin-induced platelet aggregation (HIPA) assay, in patients with heparin-induced thrombocytopenia (HIT). Platelet function test interference is related to P2Y12-receptor inhibition on healthy donor platelets by ticagrelor in the affected patient. Ticagrelor is not expected to have an impact on PF4 antibody testing for HIT. Knowledge of current treatment with ticagrelor is needed with interpretation of HIT functional tests.[44951]

      Central sleep apnea, including Cheyne-Stokes respiration, has been reported with postmarketing use of ticagrelor. Patients with central sleep apnea may experience a worsening of their symptoms with ticagrelor therapy. Recurrence or worsening of central sleep apnea or Cheyne-Stokes respiration has been reported in patients following ticagrelor rechallenge. If central sleep apnea is suspected, consider further clinical assessment.[44951]

      Revision Date: 08/11/2021, 07:36:26 PM

      References

      44951 - Brilinta (ticagrelor) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 May.60742 - Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.

      Mechanism of Action

      Ticagrelor and its major metabolite reversibly bind to the platelet P2Y12 ADP receptor thereby antagonizing ADP and preventing platelet activation. The maximum inhibition of platelet aggregation (IPA) effect of ticagrelor is reached in approximately 2 hours and maintained for at least 8 hours.[44951]

      Revision Date: 08/08/2011, 01:25:44 PM

      References

      44951 - Brilinta (ticagrelor) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 May.

      Pharmacokinetics

      Ticagrelor is administered orally. Extensive plasma protein binding (>99%) occurs with ticagrelor and the active metabolite. The volume of distribution at steady state is 88 L. Systemic exposure of the active metabolite is approximately 30—40% of ticagrelor. The main hepatic isoenzyme responsible for the metabolism of ticagrelor is CYP3A4, with CYP3A5 playing a minor role. Ticagrelor is metabolized to an active metabolite and the primary routes of elimination for ticagrelor and its metabolite are hepatic and biliary, respectively. After oral administration of radiolabeled ticagrelor, approximately 84% recovery of radioactivity was seen (58% in the feces, 26% in the urine). Recovery of ticagrelor and the active metabolite in the urine were < 1%. The mean half-life is approximately 7 hours for ticagrelor and 9 hours for the active metabolite.[44951]

       

      The maximum inhibition of platelet aggregation (IPA) effect of ticagrelor is reached in approximately 2 hours and maintained for at least 8 hours.[44951]

       

      Affected cytochrome P450 isoenzymes and drug transporters:  CYP3A4, CYP3A5, P-gp

      Both ticagrelor and its metabolite are weak inhibitors of CYP3A4/5 and inhibit the P-glycoprotein (P-gp) transporter. Ticagrelor is also a P-gp substrate. Ticagrelor and its metabolite were shown to have no inhibitory effect on CYP1A2, CYP2C19, and CYP2E1. No significant pharmacokinetic interactions were seen in studies comparing ticagrelor 90 mg twice daily to desmopressin 0.3 mcg/hr for 2 hours, atorvastatin 80 mg (CYP3A4 and P-gp substrate), levonorgestrel 0.15 mg once daily (CYP3A4 substrate), ethinyl estradiol 0.03 mg once daily (CYP3A4 substrate and inhibitor and P-gp substrate), or tolbutamide 500 mg.[44951]

      Route-Specific Pharmacokinetics

      Oral Route

      The mean absolute bioavailability of ticagrelor is 36% (range 30—42%). The maximum concentrations for ticagrelor are seen within 1.5 hours (range 1—4 h) and 2.5 hours (range 1.5—5 h) for the active metabolite. When administered as crushed tablets mixed in water either orally or via nasogastric tube, the mixture is bioequivalent to whole tablets with a median tmax of 1 hour for ticagrelor and 2 hours for the active metabolite. Ingestion of a high-fat meal has no effect on ticagrelor Cmax but does increase AUC by 21%. In contrast, a high-fat meal results in an increase in the active metabolite Cmax by 22% with no change in AUC. The drug may be taken with or without food.[44951]

      Special Populations

      Hepatic Impairment

      Ticagrelor has not been studied in patients with moderate or severe hepatic impairment. Although the AUC and Cmax of ticagrelor and the active metabolite are somewhat increased in patients with mild hepatic impairment compared to those with normal hepatic function, no adjustment in the ticagrelor dose is required for patients with mild hepatic impairment.[44951]

      Renal Impairment

      Although the AUC and Cmax of ticagrelor and the active metabolite are somewhat decreased in patients with severe renal impairment compared to those with normal renal function, no adjustment in the ticagrelor dose is required. Patients with end-stage renal disease on hemodialysis were found to have an increase of 38% and 51% in AUC and Cmax, respectively, when ticagrelor 90 mg was administered on a non-dialysis day. The AUC and Cmax of ticagrelor were similarly elevated when administered immediately prior to hemodialysis, indicating that the drug is not dialyzable. Ticagrelor's inhibition of platelet aggregation in hemodialysis patients with end-stage renal disease was similar to healthy adults with normal renal function.[44951]

      Geriatric

      Although the AUC and Cmax of ticagrelor and the active metabolite are somewhat increased in geriatric patients compared to younger patients, no adjustment in the ticagrelor dose is required.[44951]

      Gender Differences

      Although the AUC and Cmax of ticagrelor and the active metabolite are somewhat increased in females compared to males, no adjustment in the ticagrelor dose is required.[44951]

      Ethnic Differences

      Although the exposure and Cmax of ticagrelor and the active metabolite are somewhat increased in Japanese patients compared to Caucasians, no adjustment in the ticagrelor dose is required.[44951]

      Other

      Smoking

      The mean ticagrelor clearance is increased by approximately 22% in habitual smokers compared to non-smokers. No dose adjustment is necessary based on smoking status.[44951]

      Revision Date: 04/11/2019, 01:58:56 PM

      References

      44951 - Brilinta (ticagrelor) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 May.

      Pregnancy/Breast-feeding

      labor, obstetric delivery, pregnancy

      Available data from case-reports of ticagrelor use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. No adequate or well-controlled studies of ticagrelor in pregnant women exist. In animal reproduction studies, ticagrelor caused structural abnormalities at maternal doses about 5 to 7 times the maximum recommended human dose (MRHD) based on body surface area. Pup death and effects on pup growth were seen when ticagrelor was given at doses 10 times the MRHD to rats during late gestation and lactation. Ticagrelor should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.[44951] Furthermore, ticagrelor should be used with extreme caution near term and during labor and obstetric delivery because of the possibility of maternal postpartum hemorrhage.

      breast-feeding

      According to the manufacturer, it is unknown if ticagrelor or its metabolites are excreted into human breast milk. Since many drugs are excreted into human milk and due to the potentially serious adverse effects to the infant, the manufacturer states that breastfeeding is not recommended during ticagrelor therapy; thus, either ticagrelor therapy or breast-feeding should be discontinued.[44951] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.

      Revision Date: 04/10/2019, 01:56:18 PM

      References

      44951 - Brilinta (ticagrelor) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 May.

      Interactions

      Level 1 (Severe)

      • Abrocitinib
      • Avanafil
      • Defibrotide
      • Itraconazole

      Level 2 (Major)

      • Adagrasib
      • Alprazolam
      • Amoxicillin; Clarithromycin; Omeprazole
      • Apalutamide
      • Apixaban
      • Atazanavir; Cobicistat
      • Berotralstat
      • Betrixaban
      • Caplacizumab
      • Carbamazepine
      • Ceritinib
      • Clarithromycin
      • Cobicistat
      • Dabrafenib
      • Darunavir
      • Darunavir; Cobicistat
      • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
      • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
      • Delavirdine
      • Edoxaban
      • Eliglustat
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Enoxaparin
      • Enzalutamide
      • Flibanserin
      • Fosphenytoin
      • Ibritumomab Tiuxetan
      • Idelalisib
      • Indinavir
      • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
      • Isoniazid, INH; Rifampin
      • Ketoconazole
      • Lansoprazole; Amoxicillin; Clarithromycin
      • Lemborexant
      • Levoketoconazole
      • Lomitapide
      • Lonafarnib
      • Lopinavir; Ritonavir
      • Lovastatin
      • Lovastatin; Niacin
      • Lumacaftor; Ivacaftor
      • Mitotane
      • Nanoparticle Albumin-Bound Sirolimus
      • Nefazodone
      • Nelfinavir
      • Nirmatrelvir; Ritonavir
      • Nisoldipine
      • Ombitasvir; Paritaprevir; Ritonavir
      • Phenobarbital
      • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
      • Phenytoin
      • Primidone
      • Relugolix
      • Relugolix; Estradiol; Norethindrone acetate
      • Ribociclib
      • Ribociclib; Letrozole
      • Rifampin
      • Rifapentine
      • Rimegepant
      • Ritonavir
      • Rivaroxaban
      • Saquinavir
      • Sirolimus
      • St. John's Wort, Hypericum perforatum
      • Sulfinpyrazone
      • Thrombolytic Agents
      • Tipranavir
      • Topotecan
      • Tucatinib
      • Ubrogepant
      • Venetoclax
      • Vonoprazan; Amoxicillin; Clarithromycin
      • Voriconazole

      Level 3 (Moderate)

      • Abciximab
      • Acetaminophen; Aspirin
      • Acetaminophen; Aspirin, ASA; Caffeine
      • Acetaminophen; Aspirin; Diphenhydramine
      • Acetaminophen; Caffeine; Dihydrocodeine
      • Acetaminophen; Codeine
      • Acetaminophen; Hydrocodone
      • Acetaminophen; Oxycodone
      • Ado-Trastuzumab emtansine
      • Alfentanil
      • Altretamine
      • Amiodarone
      • Anagrelide
      • Antithrombin III
      • Antithymocyte Globulin
      • Aprepitant, Fosaprepitant
      • Argatroban
      • Aspirin, ASA
      • Aspirin, ASA; Butalbital; Caffeine
      • Aspirin, ASA; Caffeine
      • Aspirin, ASA; Caffeine; Orphenadrine
      • Aspirin, ASA; Carisoprodol
      • Aspirin, ASA; Carisoprodol; Codeine
      • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
      • Aspirin, ASA; Dipyridamole
      • Aspirin, ASA; Omeprazole
      • Aspirin, ASA; Oxycodone
      • Aspirin, ASA; Pravastatin
      • Atazanavir
      • Belladonna; Opium
      • Benzhydrocodone; Acetaminophen
      • Bexarotene
      • Bivalirudin
      • Brigatinib
      • Bupivacaine; Lidocaine
      • Butalbital; Acetaminophen; Caffeine; Codeine
      • Butalbital; Aspirin; Caffeine; Codeine
      • Cabotegravir; Rilpivirine
      • Cannabidiol
      • Capmatinib
      • Carvedilol
      • Celecoxib; Tramadol
      • Chlorambucil
      • Chlorpheniramine; Codeine
      • Chlorpheniramine; Dihydrocodeine; Phenylephrine
      • Chlorpheniramine; Hydrocodone
      • Cilostazol
      • Citalopram
      • Cladribine
      • Clofarabine
      • Clopidogrel
      • Cobimetinib
      • Codeine
      • Codeine; Guaifenesin
      • Codeine; Guaifenesin; Pseudoephedrine
      • Codeine; Phenylephrine; Promethazine
      • Codeine; Promethazine
      • Collagenase
      • Conivaptan
      • Crizotinib
      • Cyclosporine
      • Dabigatran
      • Daclatasvir
      • Dalteparin
      • Danazol
      • Dasatinib
      • Desirudin
      • Desvenlafaxine
      • Dexamethasone
      • Dextromethorphan; Quinidine
      • Digoxin
      • Dipyridamole
      • Dolutegravir; Rilpivirine
      • Doravirine; Lamivudine; Tenofovir disoproxil fumarate
      • Dronabinol
      • Duloxetine
      • Duvelisib
      • Efavirenz
      • Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
      • Elacestrant
      • Elbasvir; Grazoprevir
      • Emtricitabine; Rilpivirine; Tenofovir alafenamide
      • Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate
      • Emtricitabine; Tenofovir disoproxil fumarate
      • Enasidenib
      • Encorafenib
      • Eptifibatide
      • Erythromycin
      • Escitalopram
      • Etravirine
      • Everolimus
      • Ezetimibe; Simvastatin
      • Fedratinib
      • Fentanyl
      • Finerenone
      • Fish Oil, Omega-3 Fatty Acids (Dietary Supplements)
      • Fludarabine
      • Fluoxetine
      • Fluvoxamine
      • Fondaparinux
      • Fosamprenavir
      • Fostamatinib
      • Futibatinib
      • Garlic, Allium sativum
      • Gilteritinib
      • Ginger, Zingiber officinale
      • Ginkgo, Ginkgo biloba
      • Glecaprevir; Pibrentasvir
      • grapefruit juice
      • Guaifenesin; Hydrocodone
      • Guaifenesin; Hydrocodone; Pseudoephedrine
      • Heparin
      • Homatropine; Hydrocodone
      • Hydrocodone
      • Hydrocodone; Ibuprofen
      • Hydrocodone; Pseudoephedrine
      • Hydromorphone
      • Ibrutinib
      • Ibuprofen; Oxycodone
      • Icosapent ethyl
      • Iloprost
      • Inotersen
      • Intravenous Lipid Emulsions
      • Isavuconazonium
      • Istradefylline
      • Ivosidenib
      • Ixabepilone
      • Lamivudine; Tenofovir Disoproxil Fumarate
      • Lapatinib
      • Lasmiditan
      • Ledipasvir; Sofosbuvir
      • Lefamulin
      • Lenacapavir
      • Lepirudin
      • Letermovir
      • Levomilnacipran
      • Levorphanol
      • Lidocaine
      • Lidocaine; Epinephrine
      • Lidocaine; Prilocaine
      • Lomustine, CCNU
      • Loperamide
      • Loperamide; Simethicone
      • Maribavir
      • Mefloquine
      • Meperidine
      • Meperidine; Promethazine
      • Mercaptopurine, 6-MP
      • Methadone
      • Methylsulfonylmethane, MSM
      • Mifepristone
      • Milnacipran
      • Mitapivat
      • Morphine
      • Morphine; Naltrexone
      • Mycophenolate
      • Nelarabine
      • Neratinib
      • Netupitant, Fosnetupitant; Palonosetron
      • Niacin; Simvastatin
      • Nintedanib
      • Nonsteroidal antiinflammatory drugs
      • Obinutuzumab
      • Olanzapine; Fluoxetine
      • Osimertinib
      • Oxycodone
      • Oxymorphone
      • Pacritinib
      • Paroxetine
      • Pentosan
      • Pentostatin
      • Pentoxifylline
      • Pirtobrutinib
      • Platelet Glycoprotein IIb/IIIa Inhibitors
      • Posaconazole
      • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
      • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
      • Pretomanid
      • Propafenone
      • Purine analogs
      • Quinidine
      • Ranolazine
      • Remifentanil
      • Rifaximin
      • Rilpivirine
      • Selective serotonin reuptake inhibitors
      • Selpercatinib
      • Selumetinib
      • Sertraline
      • Simvastatin
      • Simvastatin; Sitagliptin
      • Sodium Phenylbutyrate; Taurursodiol
      • Sofosbuvir; Velpatasvir
      • Sofosbuvir; Velpatasvir; Voxilaprevir
      • Sorafenib
      • Sotorasib
      • Sparsentan
      • Stiripentol
      • Sufentanil
      • Talazoparib
      • Tapentadol
      • Temsirolimus
      • Tenofovir Disoproxil Fumarate
      • Tepotinib
      • Terbinafine
      • Thioguanine, 6-TG
      • Tirofiban
      • Tramadol
      • Tramadol; Acetaminophen
      • Trandolapril; Verapamil
      • Trazodone
      • Treprostinil
      • Triazolam
      • Venlafaxine
      • Verapamil
      • Verteporfin
      • Vilazodone
      • Vincristine
      • Vincristine Liposomal
      • Vinorelbine
      • Voclosporin
      • Vorapaxar
      • Vorinostat
      • Vortioxetine
      • Voxelotor
      • Warfarin

      Level 4 (Minor)

      • Aminolevulinic Acid
      • Cabozantinib
      • Dronedarone
      • Elexacaftor; tezacaftor; ivacaftor
      • Ivacaftor
      • Lumacaftor; Ivacaftor
      • Maraviroc
      • Methoxsalen
      • Photosensitizing agents (topical)
      • Simeprevir
      • Tacrolimus
      • Tenofovir Alafenamide
      • Tezacaftor; Ivacaftor
      • Vemurafenib
      • Zonisamide
      Abciximab: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding. [28435] [28436] [29816] [30141] [30142] [36055] [44951] Abrocitinib: (Contraindicated) Concurrent use with ticagrelor is contraindicated during the first 3 months of abrocitinib therapy due to an increased risk of bleeding with thrombocytopenia. After 3 months of abrocitinib therapy, monitor for increased bleeding if coadministered with ticagrelor as concurrent use may also increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and abrocitinib is a P-gp inhibitor. [44951] [67277] Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Acetaminophen; Aspirin: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Coadministration of opioid agonists, such as dihydrocodeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [30282] [44951] Acetaminophen; Codeine: (Moderate) Coadministration of opioid agonists, such as codeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Acetaminophen; Hydrocodone: (Moderate) Coadministration of opioid agonists, such as hydrocodone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Acetaminophen; Oxycodone: (Moderate) Coadministration of opioid agonists may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Adagrasib: (Major) Avoid coadministration of ticagrelor with adagrasib due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A and P-gp substrate and adagrasib is a strong CYP3A and P-gp inhibitor. Coadministration with another strong CYP3A inhibitor increased ticagrelor exposure by 7.32-fold. [44951] [68325] Ado-Trastuzumab emtansine: (Moderate) Use caution if coadministration of platelet inhibitors with ado-trastuzumab emtansine is necessary due to reports of severe and sometimes fatal hemorrhage, including intracranial bleeding, with ado-trastuzumab emtansine therapy. Consider additional monitoring when concomitant use is medically necessary. While some patients who experienced bleeding during ado-trastuzumab therapy were also receiving anticoagulation therapy, others had no known additional risk factors. [53295] Alfentanil: (Moderate) Coadministration of opioid agonists, such as alfentanil, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Alprazolam: (Major) Avoid coadministration of alprazolam and ticagrelor due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with ticagrelor, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and ticagrelor is a weak CYP3A4 inhibitor. Coadministration with another weak CYP3A4 inhibitor increased alprazolam maximum concentration by 82%, decreased clearance by 42%, and increased half-life by 16%. [28040] [44951] Altretamine: (Moderate) An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as altretamine. [6886] Aminolevulinic Acid: (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy. [6359] [6625] Amiodarone: (Moderate) Coadministration of ticagrelor and amiodarone may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and amiodarone is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] [4950] Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as clarithromycin. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp) and concomitant use with clarithromycin substantially increases ticagrelor exposure which may increase the bleeding risk. [28238] [44951] Anagrelide: (Moderate) Although anagrelide inhibits platelet aggregation at high doses, there is a potential additive risk for bleeding if anagrelide is given in combination with other agents that effect hemostasis such as ADP receptor antagonists including clopidogrel, prasugrel, ticagrelor, or ticlopidine. [28435] [28436] [30163] [36055] [44951] Antithrombin III: (Moderate) Theoretically, as a regulator of hemostasis, antithrombin III (AT III) may increase bleeding risk in patients receiving platelet inhibitors (e.g. aspirin, ASA, clopidogrel) concomitantly. Patients should be monitored for appropriate anticoagulation during coadministration of AT III and platelet inhibitors. [6880] Antithymocyte Globulin: (Moderate) An increased risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia, such as antithymocyte globulin. Platelet inhibitors should be used cautiously in patients with thrombocytopenia following the administration of antithymocyte globulin or other drugs that cause significant thrombocytopenia due to the increased risk of bleeding. [41851] Apalutamide: (Major) Avoid coadministration of ticagrelor with apalutamide due to decreased plasma concentrations of ticagrelor. Ticagrelor is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ticagrelor exposure by 86%. [44951] [62874] Apixaban: (Major) The concomitant use of apixaban and platelet inhibitors (e.g, aspirin) may increase the risk of bleeding. In the ARISTOTLE trial (comparative trial of apixaban and warfarin in patients with nonvalvular atrial fibrillation), concomitant use of aspirin increased the bleeding risk of apixaban from 1.8%/year to 3.4%/year. If given concomitantly, patients should be educated about the signs and symptoms of bleeding and be instructed to report them immediately or go to an emergency room. [52739] Aprepitant, Fosaprepitant: (Moderate) Use caution if ticagrelor and aprepitant, fosaprepitant are used concurrently and monitor for an increase in ticagrelor-related adverse effects for several days after administration of a multi-day aprepitant regimen. Ticagrelor is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of ticagrelor. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Ticagrelor is also a weak CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant (230 mg, or 1.8 times the recommended single dose) with a moderate CYP3A4 inhibitor, diltiazem, increased the aprepitant AUC 2-fold with a concomitant 1.7-fold increase in the diltiazem AUC; clinically meaningful changes in ECG, heart rate, or blood pressure beyond those induced by diltiazem alone did not occur. Information is not available regarding the use of aprepitant with weak CYP3A4 inhibitors. [30676] [40027] [44951] Argatroban: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g., clopidogrel, platelet glycoprotein IIb/IIIa inhibitors, ticlopidine, etc.) in combination with argatroban. [56982] Aspirin, ASA: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Aspirin, ASA; Butalbital; Caffeine: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] (Moderate) Coadministration of opioid agonists, such as codeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Aspirin, ASA; Caffeine: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Aspirin, ASA; Carisoprodol: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] (Moderate) Coadministration of opioid agonists, such as codeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Aspirin, ASA; Dipyridamole: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis such as ADP receptor antagonists including clopidogrel, prasugrel, ticagrelor, or ticlopidine. [28435] [28436] [36055] [44951] [5168] Aspirin, ASA; Omeprazole: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Aspirin, ASA; Oxycodone: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] (Moderate) Coadministration of opioid agonists may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Aspirin, ASA; Pravastatin: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Atazanavir: (Moderate) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as atazanavir. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with atazanavir substantially increases ticagrelor exposure which may increase the bleeding risk. [44951] Atazanavir; Cobicistat: (Major) Avoid coadministration of ticagrelor with cobicistat due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [44951] [58000] (Moderate) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as atazanavir. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with atazanavir substantially increases ticagrelor exposure which may increase the bleeding risk. [44951] Avanafil: (Contraindicated) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including ticagrelor, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day. [28315] [47165] [49866] Belladonna; Opium: (Moderate) Coadministration of opioid agonists, such as opium, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Benzhydrocodone; Acetaminophen: (Moderate) Coadministration of opioid agonists, such as benzhydrocodone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] [62889] Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking ticagrelor. Also monitor for increased bleeding. Concurrent use may increase the exposure of both drugs and the risk of adverse effects. Berotralstat is a P-gp substrate/inhibitor and a moderate CYP3A4 inhibitor; ticagrelor is a sensitive CYP3A4 substrate and P-gp substrate/inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%. [44951] [66159] Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving ticagrelor. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving ticagrelor. Coadministration of betrixaban and platelet inhibitors like ticagrelor increases the risk of bleeding; additionally, betrixaban exposure may increase further increasing bleeding risk. Monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; ticagrelor inhibits P-gp. [44951] [62037] Bexarotene: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including bexarotene. [6886] Bivalirudin: (Moderate) When used as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI), bivalirudin is intended for use with aspirin (300 to 325 mg/day PO) and has been studied only in patients receiving concomitant aspirin. Generally, an additive risk of bleeding may be seen in patients receiving other platelet inhibitors (other than aspirin). In clinical trials in patients undergoing PTCA, patients receiving bivalirudin with heparin, warfarin, or thrombolytics had increased risks of major bleeding events compared to those receiving bivalirudin alone. According to the manufacturer, the safety and effectiveness of bivalirudin have not been established when used in conjunction with platelet inhibitors other than aspirin. However, bivalirudin has been safely used as an alternative to heparin in combination with provisional use of platelet glycoprotein IIb/IIIa inhibitors during angioplasty (REPLACE-2). In addition, two major clinical trials have evaluated the use of bivalirudin in patients receiving streptokinase following acute myocardial infarction (HERO-1, HERO-2). Based on the these trials, bivalirudin may be considered an alternative to heparin therapy for use in combination with streptokinase for ST-elevation MI. Bivalirudin has not been sufficiently studied in combination with other more specific thrombolytics. [1162] [26011] [27670] [27671] [27672] [29586] Brigatinib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with brigatinib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and brigatinib is a P-gp inhibitor. [44951] [61909] Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and ticagrelor may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticagrelor inhibits CYP3A4. [32857] [44951] Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Coadministration of opioid agonists, such as codeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Cabotegravir; Rilpivirine: (Moderate) Close clinical monitoring for adverse events is advised when administering rilpivirine with ticagrelor. Use of these drugs together may result in elevated rilpivirine plasma concentrations. Ticagrelor is a weak inhibitor of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Rilpivirine is primarily metabolized by CYP3A4. [44951] [45290] Cabozantinib: (Minor) Monitor for an increase in ticagrelor-related adverse reactions if coadministration with cabozantinib is necessary. Ticagrelor is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown. [44951] [52506] [60738] Cannabidiol: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with cannabidiol as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and cannabidiol is a P-gp inhibitor. [44951] [63309] Caplacizumab: (Major) Avoid concomitant use of caplacizumab and platelet inhibitors when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs. [63940] Capmatinib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with capmatinib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and capmatinib is a P-gp inhibitor. [44951] [65377] Carbamazepine: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inducers, such as carbamazepine. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with carbamazepine substantially decreases ticagrelor exposure which may decrease the efficacy of ticagrelor. [44951] Carvedilol: (Moderate) Altered concentrations of ticagrelor and/or carvedilol may occur during coadministration. Carvedilol and ticagrelor are both substrates and inhibitors of P-glycoprotein (P-gp). Use caution if concomitant use is necessary and monitor for increased side effects. [44951] [51834] [58220] Celecoxib; Tramadol: (Moderate) Coadministration of opioid agonists, such as tramadol, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Ceritinib: (Major) Avoid coadministration of ticagrelor with ceritinib due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [44951] [57094] Chlorambucil: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as chlorambucil. [6886] Chlorpheniramine; Codeine: (Moderate) Coadministration of opioid agonists, such as codeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Coadministration of opioid agonists, such as dihydrocodeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [30282] [44951] Chlorpheniramine; Hydrocodone: (Moderate) Coadministration of opioid agonists, such as hydrocodone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Cilostazol: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of cilostazol and ticagrelor. Both agents are platelet inhibitors; therefore, concomitant use may increase the risk of bleeding. Platelet aggregation returns to normal within 96 hours of discontinuing cilostazol. [44951] [48620] Citalopram: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving ticagrelor. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [28260] [28343] [28435] Cladribine: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors. [5166] [5853] Clarithromycin: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as clarithromycin. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp) and concomitant use with clarithromycin substantially increases ticagrelor exposure which may increase the bleeding risk. [28238] [44951] Clofarabine: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors. [6466] [7557] Clopidogrel: (Moderate) Because clopidogrel and ticagrelor inhibit platelet aggregation, a potential additive risk for bleeding exists if the drugs are given in combination. Patients should be instructed to monitor for signs and symptoms of bleeding and to promptly report any bleeding events. [28434] [28435] [44951] Cobicistat: (Major) Avoid coadministration of ticagrelor with cobicistat due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [44951] [58000] Cobimetinib: (Moderate) If concurrent use of cobimetinib and ticagrelor is necessary, use caution and monitor for increased cobimetinib-related adverse effects. Cobimetinib is a CYP3A substrate in vitro as well as a P-glycoprotein (P-gp) inhibitor; ticagrelor is a weak inhibitor of both CYP3A and P-gp. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7). Simulations showed that predicted steady-state concentrations of cobimetinib at a reduced dose of 20 mg administered concurrently with short-term (less than 14 days) treatment of a moderate CYP3A inhibitor were similar to observed steady-state concentrations of cobimetinib 60 mg alone. The manufacturer of cobimetinib recommends avoiding coadministration with moderate to strong CYP3A inhibitors, and significantly reducing the dose of cobimetinib if coadministration with moderate CYP3A inhibitors cannot be avoided. Guidance is not available regarding concomitant use of cobimetinib with weak CYP3A inhibitors. [44951] [60281] Codeine: (Moderate) Coadministration of opioid agonists, such as codeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Codeine; Guaifenesin: (Moderate) Coadministration of opioid agonists, such as codeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Coadministration of opioid agonists, such as codeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Codeine; Phenylephrine; Promethazine: (Moderate) Coadministration of opioid agonists, such as codeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Codeine; Promethazine: (Moderate) Coadministration of opioid agonists, such as codeine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Collagenase: (Moderate) Cautious use of injectable collagenase by patients taking platelet inhibitors is advised. The efficacy and safety of administering injectable collagenase to a patient taking a platelet inhibitor within 7 days before the injection are unknown. Receipt of injectable collagenase may cause an ecchymosis or bleeding at the injection site. [38955] Conivaptan: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with conivaptan. Coadministration may increase the exposure of ticagrelor. Ticagrelor is a sensitive substrate of CYP3A and P-gp; conivaptan is a moderate CYP3A and P-gp inhibitor. [31764] [44951] [56579] Crizotinib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with crizotinib. Coadministration may increase the exposure of ticagrelor. Ticagrelor is a sensitive substrate of CYP3A; crizotinib is a moderate inhibitor of CYP3A. [44951] [45458] Cyclosporine: (Moderate) Coadministration of ticagrelor and cyclosporine results in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and cyclosporine is a P-gp inhibitor. No dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with ticagrelor, a mild P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like ticagrelor in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with ticagrelor, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Coadministration of ticagrelor modestly increases plasma concentrations of dabigatran; the magnitude of increase dependent on the dose and timing of ticagrelor administration. Concurrent use of dabigatran 110 mg PO twice daily and ticagrelor 90 mg PO twice daily increased the dabigatran AUC and Cmax by 26% and 29%, respectively. When coadministered with a loading dose of ticagrelor 180 mg PO, the AUC and Cmax of dabigatran increased by 49% and 65%, respectively; but when ticagrelor 180 mg was given 2 hours after dabigatran, the AUC and Cmax of dabigatran increased by only 27% and 24%, respectively. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran. [42121] [44951] [50617] Dabrafenib: (Major) The concomitant use of dabrafenib and ticagrelor may lead to decreased ticagrelor concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of ticagrelor efficacy. Dabrafenib is a moderate CYP3A4 inducer and ticagrelor is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%. [54802] Daclatasvir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with ticagrelor, a moderate CYP3A4 inhibitor, increases daclatasvir serum concentrations. In addition, the therapeutic effects of ticagrelor, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions. [44951] [60001] Dalteparin: (Moderate) Because ticagrelor inhibits platelet aggregation, a potential additive pharmacodynamic effect for bleeding exists if ticagrelor is given in combination with other agents that affect hemostasis such as warfarin, heparin, or low-molecular weight heparins (LMWHs). No significant pharmacokinetic changes were seen with ticagrelor was coadministered with heparin 100 international units and enoxaparin 1 mg/kg, and the manufacturer states ticagrelor may be administered with unfractionated heparin and low molecular weight heparins. [44951] [49946] Danazol: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors. [27253] Darunavir: (Major) Avoid coadministration of ticagrelor with darunavir due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [32432] [44951] Darunavir; Cobicistat: (Major) Avoid coadministration of ticagrelor with cobicistat due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [44951] [58000] (Major) Avoid coadministration of ticagrelor with darunavir due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [32432] [44951] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of ticagrelor with cobicistat due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [44951] [58000] (Major) Avoid coadministration of ticagrelor with darunavir due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [32432] [44951] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid the concomitant use of ticagrelor and dasabuvir; ombitasvir; paritaprevir; ritonavir. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp), and ritonavir is a potent CYP3A4 inhibitor and a P-gp inhibitor. Concomitant use is expected to increase ticagrelor exposure, which may increase bleeding risk. Ticagrelor is also a mild CYP3A4 inhibitor and P-gp inhibitor. Ritonavir, paritaprevir, and dasabuvir (minor) are CYP3A4 substrates, and dasabuvir, ombitasvir, paritaprevir, and ritonavir are all substrates of P-gp. [44951] [58664] (Major) Avoid the concomitant use of ticagrelor and ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp), and ritonavir is a potent CYP3A4 inhibitor and a P-gp inhibitor. Paritaprevir also inhibits P-gp. Concomitant use is expected to increase ticagrelor exposure, which may increase bleeding risk. Ticagrelor is also a mild CYP3A4 inhibitor and P-gp inhibitor. Ritonavir and paritaprevir are CYP3A4 substrates, and ombitasvir, paritaprevir, and ritonavir are all substrates of P-gp. [44951] [58664] [60002] (Major) Avoid the concomitant use of ticagrelor and ritonavir. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp), and ritonavir is a potent CYP3A4 inhibitor and a P-gp inhibitor. Concomitant use with ritonavir substantially increases ticagrelor exposure which may increase the bleeding risk. In addition, ticagrelor is also a mild CYP3A4 inhibitor and P-gp inhibitor. Ritonavir is a substrate of both CYP3A4 and P-gp. [44951] Dasatinib: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and ticagrelor is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant platelet inhibitors may increase the risk of hemorrhage. [60087] Defibrotide: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated. [60681] Delavirdine: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as delavirdine. Although not studied, ticagrelor is a substrate of CYP3A4/5 and concomitant use with delavirdine may increase ticagrelor exposure which may increase the bleeding risk. [28476] [44951] Desirudin: (Moderate) Desirudin should be used with caution in conjunction with drugs which affect platelet function, due to the potential for an additive risk of bleeding. [1162] [2670] [5170] [6339] Desvenlafaxine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner. [28275] [29934] Dexamethasone: (Moderate) Coadministration of ticagrelor with dexamethasone may result in decreased concentrations of ticagrelor. Use combination with caution and monitor for decreased efficacy of ticagrelor. Ticagrelor is a substrate of CYP3A4/5 and dexamethasone is a moderate CYP3A4 inducer. [44951] Dextromethorphan; Quinidine: (Moderate) Coadministration of ticagrelor and quinidine may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [11309] [44951] [6114] Digoxin: (Moderate) Monitor digoxin concentrations when used concomitantly with ticagrelor. Ticagrelor is a P-gp inhibitor and digoxin is metabolized by P-gp. [44951] Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis such as ADP receptor antagonists including clopidogrel, prasugrel, ticagrelor, or ticlopidine. [28435] [28436] [36055] [44951] [5168] Dolutegravir; Rilpivirine: (Moderate) Close clinical monitoring for adverse events is advised when administering rilpivirine with ticagrelor. Use of these drugs together may result in elevated rilpivirine plasma concentrations. Ticagrelor is a weak inhibitor of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Rilpivirine is primarily metabolized by CYP3A4. [44951] [45290] Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ticagrelor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. [28193] [44951] Dronabinol: (Moderate) Use caution if coadministration of dronabinol with ticagrelor is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; ticagrelor is a weak inhibitor of CYP2C9 and 3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. [30431] [44951] [60951] Dronedarone: (Minor) Coadministration of ticagrelor and dronedarone may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and dronedarone is a P-gp inhibitor (potency unknown). Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [36101] [44951] Duloxetine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner. [28275] [29934] Duvelisib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with duvelisib. Coadministration may increase the exposure of ticagrelor. Ticagrelor is a sensitive substrate of CYP3A; duvelisib is a moderate inhibitor of CYP3A. [44951] [63571] Edoxaban: (Major) Coadministration of edoxaban and platelet inhibitors should be avoided due to an increased risk of bleeding during concurrent use. Occasionally, short-term coadministration may be necessary in patients transitioning to and from edoxaban. Long-term coadminstration is not recommended. Promptly evaluate any signs or symptoms of blood loss in patients on concomitant therapy. [58685] Efavirenz: (Moderate) If possible, avoid use of ticagrelor with efavirenz or efavirenz-containing products (i.e., efavirenz; emtricitabine; tenofovir); coadministration may result in decreased efficacy of ticagrelor, and potentially increased adverse events of efavirenz. Ticagrelor is a substrate and weak inhibitor of CYP3A4/5. Efavirenz has been shown to induce CYP3A in vivo and is partially metabolized by CYP3A4. [28442] [44951] Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ticagrelor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. [28193] [44951] (Moderate) If possible, avoid use of ticagrelor with efavirenz or efavirenz-containing products (i.e., efavirenz; emtricitabine; tenofovir); coadministration may result in decreased efficacy of ticagrelor, and potentially increased adverse events of efavirenz. Ticagrelor is a substrate and weak inhibitor of CYP3A4/5. Efavirenz has been shown to induce CYP3A in vivo and is partially metabolized by CYP3A4. [28442] [44951] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ticagrelor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. [28193] [44951] (Moderate) If possible, avoid use of ticagrelor with efavirenz or efavirenz-containing products (i.e., efavirenz; emtricitabine; tenofovir); coadministration may result in decreased efficacy of ticagrelor, and potentially increased adverse events of efavirenz. Ticagrelor is a substrate and weak inhibitor of CYP3A4/5. Efavirenz has been shown to induce CYP3A in vivo and is partially metabolized by CYP3A4. [28442] [44951] Elacestrant: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with elacestrant as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and elacestrant is a P-gp inhibitor. [44951] [68530] Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with ticagrelor may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Ticagrelor is a substrate and mild inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of hepatotoxicity. [44951] [60523] Elexacaftor; tezacaftor; ivacaftor: (Minor) Coadministration of ticagrelor and ivacaftor may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and ivacaftor is a mild P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] [48524] Eliglustat: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of ticagrelor and eliglustat is not recommended. Ticagrelor is a weak CYP3A inhibitor and P-glycoprotein (P-gp) substrate; eliglustat is a CYP3A and CYP2D6 substrate and P-gp inhibitor. Reduce eliglustat dose to 84 mg PO once daily in extensive CYP2D6 metabolizers with hepatic impairment. Eliglustat exposure and the risk of serious adverse events may be increased. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients. In addition, coadministration of eliglustat with ticagrelor, a P-gp substrate may result in increased concentrations of ticagrelor; monitor patients closely for adverse events, including signs and symptoms of bleeding. [44951] [57803] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of ticagrelor with cobicistat due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [44951] [58000] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of ticagrelor with cobicistat due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [44951] [58000] (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ticagrelor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. [28193] [44951] Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Close clinical monitoring for adverse events is advised when administering rilpivirine with ticagrelor. Use of these drugs together may result in elevated rilpivirine plasma concentrations. Ticagrelor is a weak inhibitor of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Rilpivirine is primarily metabolized by CYP3A4. [44951] [45290] Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ticagrelor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. [28193] [44951] (Moderate) Close clinical monitoring for adverse events is advised when administering rilpivirine with ticagrelor. Use of these drugs together may result in elevated rilpivirine plasma concentrations. Ticagrelor is a weak inhibitor of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Rilpivirine is primarily metabolized by CYP3A4. [44951] [45290] Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ticagrelor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. [28193] [44951] Enasidenib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with enasidenib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and enasidenib is a P-gp inhibitor. [44951] [62181] Encorafenib: (Moderate) Coadministration of encorafenib with ticagrelor may result in increased toxicity or decreased efficacy of ticagrelor. Ticagrelor is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established. [44951] [63317] Enoxaparin: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including ticagrelor, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring. [29732] [44951] Enzalutamide: (Major) Avoid coadministration of ticagrelor with enzalutamide due to decreased plasma concentrations of ticagrelor. Ticagrelor is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ticagrelor exposure by 86%. [44951] [51727] Eptifibatide: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding. [28435] [28436] [29816] [30141] [30142] [36055] [44951] Erythromycin: (Moderate) Coadministration of ticagrelor and erythromycin may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and erythromycin is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [34329] [34331] [34332] [44951] Escitalopram: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving ticagrelor. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [28260] [28343] [28435] Etravirine: (Moderate) Coadministration of ticagrelor and etravirine may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and etravirine is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [33718] [44951] Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with ticagrelor is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and ticagrelor is a weak P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations. [44951] [49823] [49903] Ezetimibe; Simvastatin: (Moderate) Avoid simvastatin doses above 40 mg/day PO when used concomitantly with ticagrelor as concomitant use will result in higher serum concentrations of simvastatin. Simvastatin is metabolized by CYP3A4 and ticagrelor is an inhibitor of CYP3A4. [44951] Fedratinib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with fedratinib. Coadministration may increase the exposure of ticagrelor. Ticagrelor is a sensitive substrate of CYP3A; fedratinib is a moderate inhibitor of CYP3A. [44951] [64568] Fentanyl: (Moderate) Coadministration of opioid agonists, such as fentanyl, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or ticagrelor; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and ticagrelor is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased overall exposure to finerenone by 21%. [44951] [66793] Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased. [29579] Flibanserin: (Major) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including ticagrelor, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient. [49451] [60099] Fludarabine: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors. [5166] [5853] Fluoxetine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving ticagrelor. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [28260] [28343] [28435] Fluvoxamine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving ticagrelor. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [28260] [28343] [28435] Fondaparinux: (Moderate) There have been no documented pharmacokinetic interactions of fondaparinux with other drugs. However, an additive risk of bleeding may be seen in patients receiving platelet inhibitors. [6413] Fosamprenavir: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with fosamprenavir. Coadministration may increase the exposure of ticagrelor. Ticagrelor is a sensitive substrate of CYP3A; fosamprenavir is a moderate inhibitor of CYP3A. [29012] [44951] Fosphenytoin: (Major) Avoid coadministration of ticagrelor with fosphenytoin due to decreased plasma concentrations of ticagrelor. Ticagrelor is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ticagrelor exposure by 86%. [28535] [44951] [52351] Fostamatinib: (Moderate) Monitor for ticagrelor toxicities that may require ticagrelor dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a P-gp substrate may increase the concentration of the P-gp substrate. Fostamatinib is a P-gp inhibitor; ticagrelor is a substrate for P-gp. Coadministration of fostamatinib with another P-gp substrate increased the P-gp substrate AUC by 37% and Cmax by 70%. [44951] [63084] Futibatinib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with futibatinib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and futibatinib is a P-gp inhibitor. [44951] [68013] Garlic, Allium sativum: (Moderate) Use together with caution. Garlic produces clinically significant antiplatelet effects, and a risk for bleeding may occur if platelet inhibitors are given in combination with garlic. [25588] [28470] [63043] Gilteritinib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with gilteritinib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and gilteritinib is a P-gp inhibitor. [44951] [63787] Ginger, Zingiber officinale: (Moderate) Ginger inhibits thromboxane synthetase, a platelet aggregation inducer, and is a prostacyclin agonist so additive bleeding may occur if platelet inhibitors are given in combination with ginger, zingiber officinale. [28470] Ginkgo, Ginkgo biloba: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and platelet inhibitors as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug therapy. [25082] [25083] [25273] [28470] [41251] [41258] [41265] Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and ticagrelor as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and ticagrelor are both substrates and inhibitors of P-glycoprotein (P-gp). [44951] [62201] (Moderate) Caution is advised with the coadministration of pibrentasvir and ticagrelor as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and ticagrelor are substrates and inhibitors of P-glycoprotein (P-gp). [44951] [62201] Grapefruit juice: (Moderate) Concomitant use of ticagrelor and grapefruit juice may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and grapefruit is a P-gp inhibitor. Use combination with caution and monitor patients for evidence of bleeding. [44951] [5822] Guaifenesin; Hydrocodone: (Moderate) Coadministration of opioid agonists, such as hydrocodone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Coadministration of opioid agonists, such as hydrocodone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Heparin: (Moderate) Because ticagrelor inhibits platelet aggregation, a potential additive pharmacodynamic effect for bleeding exists if ticagrelor is given in combination with other agents that affect hemostasis such as heparin. No significant pharmacokinetic changes were seen with ticagrelor was coadministered with heparin 100 international units and enoxaparin 1 mg/kg, and the manufacturer states ticagrelor may be administered with unfractionated heparin and low molecular weight heparins. [44951] Homatropine; Hydrocodone: (Moderate) Coadministration of opioid agonists, such as hydrocodone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Hydrocodone: (Moderate) Coadministration of opioid agonists, such as hydrocodone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Hydrocodone; Ibuprofen: (Moderate) Coadministration of opioid agonists, such as hydrocodone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Hydrocodone; Pseudoephedrine: (Moderate) Coadministration of opioid agonists, such as hydrocodone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Hydromorphone: (Moderate) Coadministration of opioid agonists, such as hydromorphone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with platelet function such as platelet inhibitors; the risk of bleeding may be increased. If coadministration with platelet inhibitors is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia. [41826] Ibrutinib: (Moderate) The concomitant use of ibrutinib and antiplatelet agents such as ticagrelor may increase the risk of bleeding; monitor patients for signs of bleeding. Severe bleeding events have occurred with ibrutinib therapy including intracranial hemorrhage, GI bleeding, hematuria, and post procedural hemorrhage; some events were fatal. The mechanism for bleeding with ibrutinib therapy is not well understood. [56410] Ibuprofen; Oxycodone: (Moderate) Coadministration of opioid agonists may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Icosapent ethyl: (Moderate) Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). Because omega-3 fatty acids inhibit platelet aggregation, caution is advised when icosapent ethyl is used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 36 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant icosapent ethyl therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly. [3535] [5879] [6320] [7299] Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ticagrelor, a CYP3A substrate, as ticagrelor toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. [44951] [57675] Iloprost: (Moderate) When used concurrently with platelet inhibitors, inhaled iloprost may increase the risk of bleeding. [7537] Indinavir: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as indinavir. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with indinavir substantially increases ticagrelor exposure which may increase the bleeding risk. [44951] Inotersen: (Moderate) Use caution with concomitant use of inotersen and ADP receptor antagonists due to the potential risk of bleeding from thrombocytopenia. Consider discontinuation of ADP receptor antagonists in a patient taking inotersen with a platelet count of less than 50,000 per microliter. [63624] Intravenous Lipid Emulsions: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased. [29579] Isavuconazonium: (Moderate) Coadministration of ticagrelor and isavuconazonium may result in increased exposure to ticagrelor which may increase the bleeding risk. In addition, the exposure to isavuconazonium may be increased resulting in potential adverse effects. Ticagrelor is a substrate and inhibitor of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together. [44951] [59042] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inducers, such as rifampin. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with rifampin substantially decreases ticagrelor exposure which may decrease the efficacy of ticagrelor. [30314] [44951] Isoniazid, INH; Rifampin: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inducers, such as rifampin. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with rifampin substantially decreases ticagrelor exposure which may decrease the efficacy of ticagrelor. [30314] [44951] Istradefylline: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with istradefylline as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and istradefylline is a P-gp inhibitor. [44951] [64590] Itraconazole: (Contraindicated) Ticagrelor is contraindicated for use during and for up to 2 weeks after discontinuation of itraconazole treatment. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp) and concomitant use with itraconazole substantially increases ticagrelor exposure which may increase the bleeding risk. [27983] [40233] [44951] Ivacaftor: (Minor) Coadministration of ticagrelor and ivacaftor may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and ivacaftor is a mild P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] [48524] Ivosidenib: (Moderate) Monitor for loss of efficacy of ticagrelor during coadministration of ivosidenib; a ticagrelor dose adjustment may be necessary. Ticagrelor is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased ticagrelor concentrations. [44951] [63368] Ixabepilone: (Moderate) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of ticagrelor is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and ticagrelor is a weak CYP3A inhibitor. [33653] [44951] Ketoconazole: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as ketoconazole. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp) and concomitant use with ketoconazole substantially increases ticagrelor exposure which may increase the bleeding risk. [44951] Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ticagrelor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. [28193] [44951] Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as clarithromycin. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp) and concomitant use with clarithromycin substantially increases ticagrelor exposure which may increase the bleeding risk. [28238] [44951] Lapatinib: (Moderate) Monitor for an increased risk of treatment-related adverse reactions including bleeding if coadministration of ticagrelor and lapatinib are necessary. Both drugs are P-glycoprotein (P-gp) substrates and inhibitors. Increased plasma concentrations of lapatinib are likely. Exposure to ticagrelor may also increase. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. [33192] [44951] Lasmiditan: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with lasmiditan as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and lasmiditan is a P-gp inhibitor. [44951] [64685] Ledipasvir; Sofosbuvir: (Moderate) Coadministration of ticagrelor and ledipasvir; sofosbuvir may result in increased exposure to all three drugs, which may increase the bleeding risk. Both ledipasvir and ticagrelor are P-glycoprotein (P-gp) substrates and inhibitors; sofosbuvir is a P-gp substrate. No dose adjustment is recommended by the manufacturer. Use combination with caution and monitor for evidence of bleeding. [44951] [58167] Lefamulin: (Moderate) Monitor for increased bleeding and lefamulin-related adverse effects if oral lefamulin is administered with ticagrelor as concurrent use may increase exposure from both drugs; an interaction is not expected with intravenous lefamulin. Ticagrelor is a sensitive substrate of CYP3A and a P-gp inhibitor; lefamulin is a CYP3A4 and P-gp substrate and CYP3A4 moderate inhibitor. [44951] [64576] Lemborexant: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with ticagrelor as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ticagrelor is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold. [44951] [64870] Lenacapavir: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with lenacapavir. Coadministration may increase the exposure of ticagrelor. Ticagrelor is a CYP3A and P-gp substrate; lenacapavir is a moderate CYP3A and P-gp inhibitor. [44951] [68383] Lepirudin: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g., clopidogrel, platelet glycoprotein IIb/IIIa inhibitors, ticlopidine, etc.) in combination with lepirudin. [28723] Letermovir: (Moderate) Administering letermovir with ticagrelor may increase ticagrelor concentration and risk for adverse events (e.g., dyspnea, bleeding). Avoid coadministration in patients also receiving cyclosporine, because the magnitude of this interaction may be increased. Ticagrelor is primarily metabolized by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. [44951] [62611] Levoketoconazole: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as ketoconazole. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp) and concomitant use with ketoconazole substantially increases ticagrelor exposure which may increase the bleeding risk. [44951] Levomilnacipran: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of levomilnacipran and platelet inhibitors. Serotonin-norepinephrine reuptake inhibitors (SNRIs) affect platelet activation; therefore, concomitant use may increase the risk of bleeding. [28435] [55469] Levorphanol: (Moderate) Coadministration of opioid agonists, such as levorphanol, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Lidocaine: (Moderate) Concomitant use of systemic lidocaine and ticagrelor may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticagrelor inhibits CYP3A4. [32857] [44951] Lidocaine; Epinephrine: (Moderate) Concomitant use of systemic lidocaine and ticagrelor may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticagrelor inhibits CYP3A4. [32857] [44951] Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and ticagrelor may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticagrelor inhibits CYP3A4. [32857] [44951] Lomitapide: (Major) Concomitant use of lomitapide and ticagrelor may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Ticagrelor is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. [52698] Lomustine, CCNU: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as lomustine. [6886] Lonafarnib: (Major) Avoid coadministration of ticagrelor with lonafarnib due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions; lonafarnib exposure may also be increased. Ticagrelor is a sensitive CYP3A4 and P-gp substrate and weak CYP3A4 inhibitor; lonafarnib is a sensitive CYP3A4 substrate and P-gp and strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by approximately 7-fold. [44951] [66129] Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with ticagrelor. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and ticagrelor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold. [33607] [44951] Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with ticagrelor. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and ticagrelor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold. [33607] [44951] Lopinavir; Ritonavir: (Major) Avoid the concomitant use of ticagrelor and ritonavir. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp), and ritonavir is a potent CYP3A4 inhibitor and a P-gp inhibitor. Concomitant use with ritonavir substantially increases ticagrelor exposure which may increase the bleeding risk. In addition, ticagrelor is also a mild CYP3A4 inhibitor and P-gp inhibitor. Ritonavir is a substrate of both CYP3A4 and P-gp. [44951] Lovastatin: (Major) Avoid lovastatin doses higher than 40 mg/day when used concomitantly with ticagrelor as concomitant use will result in higher serum concentrations of lovastatin. Lovastatin is metabolized by CYP3A4 and ticagrelor is an inhibitor of CYP3A4. [44951] Lovastatin; Niacin: (Major) Avoid lovastatin doses higher than 40 mg/day when used concomitantly with ticagrelor as concomitant use will result in higher serum concentrations of lovastatin. Lovastatin is metabolized by CYP3A4 and ticagrelor is an inhibitor of CYP3A4. [44951] Lumacaftor; Ivacaftor: (Major) Avoid concurrent use of lumacaftor; ivacaftor and ticagrelor; coadministration may result in significantly reduced ticagrelor exposure and efficacy. Ticagrelor is primarily metabolized by CYP3A; ticagrelor and its active metabolite are also P-glycoprotein (P-gp) substrates. Lumacaftor is a strong CYP3A inducer; in vitro data suggest lumacaftor; ivacaftor may also induce and/or inhibit P-gp. Although induction of ticagrelor metabolism through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Additionally, ivacaftor is a CYP3A substrate and in vitro metabolism studies suggest ticagrelor and its active metabolite are weak CYP3A4 inhibitors. Although ivacaftor exposure could theoretically be increased when given with a CYP3A inhibitor, ivacaftor; lumacaftor dosage adjustments are not recommended with concomitant use of a mild CYP3A inhibitor such as ticagrelor due to the induction effects of lumacaftor. [44951] [59891] Lumacaftor; Ivacaftor: (Minor) Coadministration of ticagrelor and ivacaftor may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and ivacaftor is a mild P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] [48524] Maraviroc: (Minor) Use caution if coadministration of maraviroc with ticagrelor is necessary due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A4 and P-glycoprotein substrate (P-gp) and ticagrelor is a weak CYP3A4 and P-gp inhibitor. Monitor for an increase in adverse effects with concomitant use. [33473] [44951] Maribavir: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with maribavir as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and maribavir is a P-gp inhibitor. [44951] [67137] Mefloquine: (Moderate) Coadministration of ticagrelor and mefloquine may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and mefloquine is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [11307] [44951] Meperidine: (Moderate) Coadministration of opioid agonists, such as meperidine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Meperidine; Promethazine: (Moderate) Coadministration of opioid agonists, such as meperidine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Mercaptopurine, 6-MP: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors. [5166] [5853] Methadone: (Moderate) Coadministration of opioid agonists, such as methadone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Methoxsalen: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy. [6466] [6625] Methylsulfonylmethane, MSM: (Moderate) Increased effects from concomitant anticoagulant drugs including increased bruising or blood in the stool have been reported in patients taking methylsulfonylmethane, MSM. Although these effects have not been confirmed in published medical literature or during clinical studies, clinicians should consider using methylsulfonylmethane, MSM with caution in patients who are taking anticoagulants or antiplatelets including clopidogrel until data confirming the safety of these drug combinations are available. During one of the available, published clinical trials in patients with osteoarthritis, those patients with bleeding disorders or using anticoagulants or antiplatelets were excluded from enrollment. Patients who choose to consume methylsulfonylmethane, MSM while receiving clopidogrel should be observed for increased bleeding. [32984] [32986] Mifepristone: (Moderate) Use together with caution and monitor for evidence of increased antiplatelet effect, as well as side effects such as bleeding and dyspnea. CYP3A inhibitors may increase ticagrelor exposure and so increase the risk of dyspnea, bleeding, and other adverse events. No dose adjustment has been recommended. Ticagrelor is a CYP3A4 and P-glycoprotein (P-gp) substrate. Mifepristone inhibits CYP3A4 and may be a P-gp inhibitor. Due to the slow elimination of mifepristone from the body, any interactions that occur may be prolonged. [28003] [44951] [48697] Milnacipran: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of milnacipran and platelet inhibitors. Serotonin-norepinephrine reuptake inhibitors (SNRIs) affect platelet activation; therefore, concomitant use may increase the risk of bleeding. [23431] [28435] Mitapivat: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with mitapivat as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and mitapivat is a P-gp inhibitor. [44951] [67403] Mitotane: (Major) Avoid the concomitant use of mitotane with ticagrelor due to decreased ticagrelor exposure and efficacy. Mitotane is a strong CYP3A4 inducer and ticagrelor is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of ticagrelor. [41934] [44951] Morphine: (Moderate) Coadministration of opioid agonists, such as morphine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Morphine; Naltrexone: (Moderate) Coadministration of opioid agonists, such as morphine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Mycophenolate: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia. [4873] Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid coadministration of sirolimus with ticagrelor as concurrent use may increase sirolimus exposure and risk of toxicity. Alternative agents with lesser interaction potential with sirolimus should be considered. Sirolimus is a CYP3A and P-gp substrate and ticagrelor is a weak CYP3A and P-gp inhibitor. [28610] [44951] [67136] Nefazodone: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as nefazodone. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with nefazodone substantially increases ticagrelor exposure which may increase the bleeding risk. [44951] Nelarabine: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors. [8493] Nelfinavir: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as nelfinavir. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with nelfinavir substantially increases ticagrelor exposure which may increase the risk of bleeding. [44951] Neratinib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with neratinib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-glycoprotein (P-gp) substrate and neratinib is a P-gp inhibitor. [44951] [62127] Netupitant, Fosnetupitant; Palonosetron: (Moderate) Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4, such as ticagrelor. The plasma concentrations of ticagrelor can increase when co-administered with netupitant; the inhibitory effect on CYP3A4 can last for multiple days. [44951] [58171] Niacin; Simvastatin: (Moderate) Avoid simvastatin doses above 40 mg/day PO when used concomitantly with ticagrelor as concomitant use will result in higher serum concentrations of simvastatin. Simvastatin is metabolized by CYP3A4 and ticagrelor is an inhibitor of CYP3A4. [44951] Nintedanib: (Moderate) Dual inhibitors of P-glycoprotein (P-gp) and CYP3A4, such as ticagrelor, are expected to increase the exposure and clinical effect of nintedanib. If use together is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity (nausea, vomiting, diarrhea, abdominal pain, loss of appetite), headache, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of nintedanib therapy may be necessary. Ticagrelor is a mild inhibitor of both P-gp and CYP3A4; nintedanib is a P-gp substrate and a minor CYP3A4 substrate. In drug interactions studies, administration of nintedanib with a dual P-gp and CYP3A4 inhibitor increased nintedanib AUC by 60%. [44951] [58203] Nirmatrelvir; Ritonavir: (Major) Avoid the concomitant use of ticagrelor and ritonavir. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp), and ritonavir is a potent CYP3A4 inhibitor and a P-gp inhibitor. Concomitant use with ritonavir substantially increases ticagrelor exposure which may increase the bleeding risk. In addition, ticagrelor is also a mild CYP3A4 inhibitor and P-gp inhibitor. Ritonavir is a substrate of both CYP3A4 and P-gp. [44951] (Major) Consider temporary discontinuation of ticagrelor during treatment with ritonavir-boosted nirmatrelvir and for at least 2 to 3 days after treatment completion. For patients at very high risk of thrombosis, consider prescribing an alternative antiplatelet or COVID-19 therapy. Coadministration may increase ticagrelor exposure resulting in increased toxicity. Ticagrelor is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor. [65314] Nisoldipine: (Major) Avoid coadministration of nisoldipine with ticagrelor due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and ticagrelor is a weak CYP3A4 inhibitor. [29088] [44951] Nonsteroidal antiinflammatory drugs: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Obinutuzumab: (Moderate) Fatal hemorrhagic events have been reported in patients treated with obinutuzumab; all events occured during cycle 1. Monitor all patients for thrombocytopenia and bleeding, and consider withholding concomitant medications which may increase bleeding risk (i.e., anticoagulants, platelet inhibitors), especially during the first cycle. [56353] Olanzapine; Fluoxetine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving ticagrelor. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [28260] [28343] [28435] Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid the concomitant use of ticagrelor and dasabuvir; ombitasvir; paritaprevir; ritonavir. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp), and ritonavir is a potent CYP3A4 inhibitor and a P-gp inhibitor. Concomitant use is expected to increase ticagrelor exposure, which may increase bleeding risk. Ticagrelor is also a mild CYP3A4 inhibitor and P-gp inhibitor. Ritonavir, paritaprevir, and dasabuvir (minor) are CYP3A4 substrates, and dasabuvir, ombitasvir, paritaprevir, and ritonavir are all substrates of P-gp. [44951] [58664] (Major) Avoid the concomitant use of ticagrelor and ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp), and ritonavir is a potent CYP3A4 inhibitor and a P-gp inhibitor. Paritaprevir also inhibits P-gp. Concomitant use is expected to increase ticagrelor exposure, which may increase bleeding risk. Ticagrelor is also a mild CYP3A4 inhibitor and P-gp inhibitor. Ritonavir and paritaprevir are CYP3A4 substrates, and ombitasvir, paritaprevir, and ritonavir are all substrates of P-gp. [44951] [58664] [60002] (Major) Avoid the concomitant use of ticagrelor and ritonavir. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp), and ritonavir is a potent CYP3A4 inhibitor and a P-gp inhibitor. Concomitant use with ritonavir substantially increases ticagrelor exposure which may increase the bleeding risk. In addition, ticagrelor is also a mild CYP3A4 inhibitor and P-gp inhibitor. Ritonavir is a substrate of both CYP3A4 and P-gp. [44951] Osimertinib: (Moderate) Monitor for an increase in ticagrelor-related adverse reactions, including bleeding, if coadministration with osimertinib is necessary. Ticagrelor is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. [44951] [60297] Oxycodone: (Moderate) Coadministration of opioid agonists may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Oxymorphone: (Moderate) Coadministration of opioid agonists, such as oxymorphone, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Pacritinib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with pacritinib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and pacritinib is a P-gp inhibitor. [44951] [67427] Paroxetine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving ticagrelor. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [28260] [28343] [28435] Pentosan: (Moderate) Pentosan is a weak anticoagulant. Pentosan has 1/15 the anticoagulant activity of heparin. An additive risk of bleeding may be seen in patients receiving other platelet inhibitors in combination with pentosan. [40043] Pentostatin: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors. [5166] [5853] Pentoxifylline: (Moderate) A potential additive risk for bleeding exists if platelet inhibitors are given in combination with other agents that affect hemostasis such as pentoxifylline. [28436] [29575] Phenobarbital: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inducers, such as phenobarbital. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with phenobarbital substantially decreases ticagrelor exposure which may decrease the efficacy of ticagrelor. [44951] Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inducers, such as phenobarbital. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with phenobarbital substantially decreases ticagrelor exposure which may decrease the efficacy of ticagrelor. [44951] Phenytoin: (Major) Avoid coadministration of ticagrelor with phenytoin due to decreased plasma concentrations of ticagrelor. Ticagrelor is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ticagrelor exposure by 86%. [44951] [52351] Photosensitizing agents (topical): (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy. [6359] [6625] Pirtobrutinib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with pirtobrutinib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and pirtobrutinib is a P-gp inhibitor. [44951] [68520] Platelet Glycoprotein IIb/IIIa Inhibitors: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding. [28435] [28436] [29816] [30141] [30142] [36055] [44951] Posaconazole: (Moderate) Coadministration of ticagrelor and posaconazole may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and posaconazole is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [11322] [44951] Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Prasterone is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments. [30054] Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Prasterone is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments. [30054] Pretomanid: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with pretomanid as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and pretomanid is a P-gp inhibitor. [44951] [64561] Primidone: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inducers, such as primidone. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with primidone may substantially decrease ticagrelor exposure which may decrease the efficacy of ticagrelor. [22005] [44951] [57046] [57048] Propafenone: (Moderate) Coadministration of ticagrelor and propafenone may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and propafenone is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] [5471] Purine analogs: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors. [5166] [5853] Quinidine: (Moderate) Coadministration of ticagrelor and quinidine may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [11309] [44951] [6114] Ranolazine: (Moderate) Coadministration of ticagrelor and ranolazine may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and ranolazine is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] Relugolix: (Major) Avoid concomitant use of relugolix and oral ticagrelor. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer ticagrelor at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and ticagrelor is a P-gp inhibitor. [44951] [66183] Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral ticagrelor. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer ticagrelor at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and ticagrelor is a P-gp inhibitor. [44951] [66183] Remifentanil: (Moderate) Coadministration of opioid agonists, such as remifentanil, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Ribociclib: (Major) Avoid coadministration of ticagrelor with ribociclib due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [44951] [61816] Ribociclib; Letrozole: (Major) Avoid coadministration of ticagrelor with ribociclib due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [44951] [61816] Rifampin: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inducers, such as rifampin. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with rifampin substantially decreases ticagrelor exposure which may decrease the efficacy of ticagrelor. [30314] [44951] Rifapentine: (Major) Avoid coadministration of ticagrelor with rifapentine due to decreased plasma concentrations of ticagrelor. Ticagrelor is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ticagrelor exposure by 86%. [44951] [65685] Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with ticagrelor is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and ticagrelor is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold. [29289] [44951] Rilpivirine: (Moderate) Close clinical monitoring for adverse events is advised when administering rilpivirine with ticagrelor. Use of these drugs together may result in elevated rilpivirine plasma concentrations. Ticagrelor is a weak inhibitor of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Rilpivirine is primarily metabolized by CYP3A4. [44951] [45290] Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with ticagrelor; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and ticagrelor is a P-gp inhibitor. [44951] [65052] Ritonavir: (Major) Avoid the concomitant use of ticagrelor and ritonavir. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp), and ritonavir is a potent CYP3A4 inhibitor and a P-gp inhibitor. Concomitant use with ritonavir substantially increases ticagrelor exposure which may increase the bleeding risk. In addition, ticagrelor is also a mild CYP3A4 inhibitor and P-gp inhibitor. Ritonavir is a substrate of both CYP3A4 and P-gp. [44951] Rivaroxaban: (Major) Avoid concurrent administration of platelet inhibitors with rivaroxaban unless the benefit outweighs the risk of increased bleeding. An increase in bleeding time to 45 minutes was observed in 2 drug interaction studies where another platelet inhibitor and rivaroxaban (15 mg single dose) were coadministered in healthy subjects. In the first study, the increase in bleeding time to 45 minutes was observed in approximately 45% of patients. Approximately 30% of patients in the second study had the event. The change in bleeding time was approximately twice the maximum increase seen with either drug alone. No change in the pharmacokinetic parameters of either drug were noted. The coadministration of rivaroxaban and ticagrelor should be undertaken with caution in patients with renal impairment; it is unclear whether a clinically significant interaction occurs when these 2 drugs are coadministered to patients with normal renal function. Ticagrelor is a combined mild CYP3A4 inhibitor and mild P-glycoprotein (P-gp) inhibitor. Rivaroxaban is a substrate of CYP3A4/5 and the P-gp transporter. Coadministration in patients with renal impairment may result in increased exposure to rivaroxaban compared with patients with normal renal function and no inhibitor use since both pathways of elimination are affected. While an increase in exposure to rivaroxaban may be expected, results from an analysis of the ROCKET-AF trial which allowed concomitant administration of rivaroxaban and a combined P-gp inhibitor and weak or moderate CYP3A4 inhibitor did not show an increased risk of bleeding in patients with CrCl 30 to less than 50 mL/minute. [44854] [44951] Saquinavir: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as saquinavir. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp) and concomitant use with saquinavir substantially increases ticagrelor exposure which may increase the bleeding risk. [28995] [44951] Selective serotonin reuptake inhibitors: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving ticagrelor. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [28260] [28343] [28435] Selpercatinib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with selpercatinib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and selpercatinib is a P-gp inhibitor. [44951] [65387] Selumetinib: (Moderate) Closely monitor for bleeding if coadministration of selumetinib and platelet inhibitors is necessary as concurrent use may increase the bleeding risk; adjust the platelet inhibitor dose as appropriate. Selumetinib contains vitamin E which can inhibit platelet aggregation. [65246] Sertraline: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving ticagrelor. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [28260] [28343] [28435] Simeprevir: (Minor) Coadministration of ticagrelor and simeprevir may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and simeprevir is a mild P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] [56471] Simvastatin: (Moderate) Avoid simvastatin doses above 40 mg/day PO when used concomitantly with ticagrelor as concomitant use will result in higher serum concentrations of simvastatin. Simvastatin is metabolized by CYP3A4 and ticagrelor is an inhibitor of CYP3A4. [44951] Simvastatin; Sitagliptin: (Moderate) Avoid simvastatin doses above 40 mg/day PO when used concomitantly with ticagrelor as concomitant use will result in higher serum concentrations of simvastatin. Simvastatin is metabolized by CYP3A4 and ticagrelor is an inhibitor of CYP3A4. [44951] Sirolimus: (Major) Avoid coadministration of sirolimus with ticagrelor as concurrent use may increase sirolimus exposure and risk of toxicity. Alternative agents with lesser interaction potential with sirolimus should be considered. Sirolimus is a CYP3A and P-gp substrate and ticagrelor is a weak CYP3A and P-gp inhibitor. [28610] [44951] [67136] Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with taurursodiol as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and taurursodiol is a P-gp inhibitor. [44951] [68007] Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with ticagrelor. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, ticagrelor is a weak inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate. [44951] [60911] Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of ticagrelor, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently. [44951] [62131] (Moderate) Use caution when administering velpatasvir with ticagrelor. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, ticagrelor is a weak inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate. [44951] [60911] Sorafenib: (Moderate) Monitor for an increase in ticagrelor-related adverse reactions, including bleeding, if coadministration with sorafenib is necessary. Ticagrelor is a P-glycoprotein (P-gp) substrate. Sorafenib inhibits P-gp in vitro and may increase the concentrations of concomitantly administered drugs that are P-gp substrates. [31832] [44951] Sotorasib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with sotorasib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and sotorasib is a P-gp inhibitor. [44951] [66700] Sparsentan: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with sparsentan as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and sparsentan is a P-gp inhibitor. [44951] [68641] St. John's Wort, Hypericum perforatum: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inducers, such as St. John's Wort, Hypericum perforatum. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with St. John's Wort may substantially decrease ticagrelor exposure which may decrease the efficacy of ticagrelor. [44951] [57202] [57852] Stiripentol: (Moderate) Consider a dose adjustment of ticagrelor when coadministered with stiripentol. Coadministration may alter plasma concentrations of ticagrelor resulting in an increased risk of adverse reactions and/or decreased efficacy. Ticagrelor is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions. [44951] [63456] Sufentanil: (Moderate) Coadministration of opioid agonists, such as sufentanil, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [30966] [44951] [63731] Sulfinpyrazone: (Major) Sulfinpyrazone, when used as a uricosuric agent should be avoided when possible with concurrent platelet inhibitors due to potential for additive antiplatelet effects and increased bleeding risk. [5125] Tacrolimus: (Minor) Coadministration of ticagrelor and tacrolimus may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate. Tacrolimus may be a P-gp inhibitor; however, data are conflicting. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [34512] [44951] [52498] Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ticagrelor is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ticagrelor is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. [44951] [63651] Tapentadol: (Moderate) Coadministration of opioid agonists, such as tapentadol, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Temsirolimus: (Moderate) Monitor for an increase in temsirolimus- and ticagrelor-related adverse reactions if coadministration is necessary. Both drugs are P-glycoprotein (P-gp) substrates and inhibitors. Concomitant use is likely to lead to increased concentrations of temsirolimus and ticagrelor. [44951] [50586] Tenofovir Alafenamide: (Minor) Close clinical monitoring for adverse events is advised when administering tenofovir alafenamide with ticagrelor. Use of these drugs together may result in elevated tenofovir plasma concentrations. Ticagrelor is an inhibitor of the drug transporter P-glycoprotein (P-gp).Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor. [44951] [61413] Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as ticagrelor. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. [28193] [44951] Tepotinib: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with tepotinib as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and tepotinib is a P-gp inhibitor. [44951] [66372] Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ticagrelor. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; ticagrelor is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered. [37590] [43880] [43881] [44951] [56538] Tezacaftor; Ivacaftor: (Minor) Coadministration of ticagrelor and ivacaftor may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and ivacaftor is a mild P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] [48524] Thioguanine, 6-TG: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors. [5166] [5853] Thrombolytic Agents: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution. [36055] [48620] Tipranavir: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as tipranavir. Although not studied, ticagrelor is a substrate of CYP3A4/5 and concomitant use with tipranavir may increase ticagrelor exposure which may increase the bleeding risk. [31320] [44951] Tirofiban: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding. [28435] [28436] [29816] [30141] [30142] [36055] [44951] Topotecan: (Major) Avoid coadministration of ticagrelor with oral topotecan due to increased topotecan exposure; ticagrelor may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and ticagrelor is a weak P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone. [33536] [33578] [44951] [46322] Tramadol: (Moderate) Coadministration of opioid agonists, such as tramadol, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Tramadol; Acetaminophen: (Moderate) Coadministration of opioid agonists, such as tramadol, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Trandolapril; Verapamil: (Moderate) Coadministration of ticagrelor and verapamil may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and verapamil is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] [56565] Trazodone: (Moderate) Platelet aggregation may be impaired by trazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking trazodone concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [38831] Treprostinil: (Moderate) Monitor patients for signs and symptoms of bleeding if treprostinil is administered with ticagrelor. Treprostinil inhibits platelet aggregation; ticagrelor is a platelet inhibitor. Coadministration increases the risk of bleeding. [30210] [44951] Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with ticagrelor and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and ticagrelor is a moderate/weak CYP3A inhibitor. [41543] [44951] Tucatinib: (Major) Avoid coadministration of ticagrelor with tucatinib due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 and P-glycoprotein (P-gp) substrate; tucatinib is a strong CYP3A4 inhibitor and P-gp inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [44951] [65295] Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with ticagrelor. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 and P-gp substrate; ticagrelor is a weak CYP3A4 inhibitor and a P-gp inhibitor. [44951] [64874] Vemurafenib: (Minor) Coadministration of ticagrelor and vemurafenib may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and vemurafenib is a mild P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] [45335] Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with ticagrelor due to the potential for increased venetoclax exposure. Additionally, ticagrelor exposure may be increased. Resume the original venetoclax dose 2 to 3 days after discontinuation of ticagrelor. Venetoclax is a CYP3A4 and P-glycoprotein (P-gp) substrate and P-gp inhibitor; ticagrelor is a CYP3A4 (weak) and P-gp inhibitor and P-gp substrate. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study. [44951] [60706] Venlafaxine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner. [28275] Verapamil: (Moderate) Coadministration of ticagrelor and verapamil may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and verapamil is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding. [44951] [56565] Verteporfin: (Moderate) Use caution if coadministration of verteporfin with platelet inhibitors is necessary due to the risk of decreased verteporfin efficacy. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease platelet aggregation could decrease the efficacy of verteporfin therapy. [30003] Vilazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with salicylates or other platelet inhibitors and to promptly report any bleeding events to the practitioner. Platelet aggregation may be impaired by vilazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., aspirin, cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). [43177] Vincristine Liposomal: (Moderate) Ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor, and vincristine is a CYP3A and P-gp substrate. Coadministration may increase vincristine concentrations; monitor patients for vincristine toxicity if these drugs are used together. [29472] [44951] Vincristine: (Moderate) Ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor, and vincristine is a CYP3A and P-gp substrate. Coadministration may increase vincristine concentrations; monitor patients for vincristine toxicity if these drugs are used together. [29472] [44951] Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ticagrelor is necessary. Vinorelbine is a CYP3A4 substrate and ticagrelor is a weak CYP3A4 inhibitor. [44951] [56871] Voclosporin: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with voclosporin as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and voclosporin is a P-gp inhibitor. [44951] [66336] Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inhibitors, such as clarithromycin. Ticagrelor is a substrate of CYP3A4/5 and P-glycoprotein (P-gp) and concomitant use with clarithromycin substantially increases ticagrelor exposure which may increase the bleeding risk. [28238] [44951] Vorapaxar: (Moderate) Because vorapaxar inhibits platelet aggregation, a potential additive risk for bleeding exists if vorapaxar is given in combination with other agents that affect hemostasis such as ADP receptor antagonists including clopidogrel, prasugrel, ticagrelor, or ticlopidine. [28435] [28436] [36055] [44951] [57151] Voriconazole: (Major) Avoid coadministration of ticagrelor with voriconazole due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold. [28158] [44951] Vorinostat: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of ticagrelor and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors. [32789] [44951] Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [56041] Voxelotor: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with voxelotor. Coadministration may increase the exposure of ticagrelor. Ticagrelor is a sensitive substrate of CYP3A; voxelotor is a moderate inhibitor of CYP3A. [44951] [64778] Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with ticagrelor is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Ticagrelor is a weak CYP3A4 inhibitor and warfarin is a CYP3A4 substrate. Also, because ticagrelor inhibits platelet aggregation, additive risk for bleeding is possible when given in combination with anticoagulants such as warfarin. [28549] [44951] Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and ticagrelor is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates. [28843] [44951]
      Revision Date: 05/04/2023, 01:35:00 AM

      References

      1162 - Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991;115:787-96.2670 - Lanza FL. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol 1998;93:2037-2046.3535 - Bender NK, Kraynak MA, Chiquette E, et al. Effects of marine fish oils on the anticoagulation status of patients receiving chronic warfarin therapy. J Thromb Thrombolysis 1998;5:257-61.4873 - Myfortic (mycophenolate sodium) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2022 Mar.4950 - Pacerone (amiodarone) tablets package insert. Maple Grove, MN: Upsher-Smith Laboratories, LLC.; 2018 Nov.5125 - Bailey, R.R, and Reddy, J. Potentiation of warfarin action by sulphinpyrazone. Lancet 1980;1:254.5166 - Ticlid (ticlopidine) package insert. Nutley, NJ: Roche Laboratories, Inc.; 2005 Dec.5168 - Persantine (dipyridamole) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2003 May.5170 - Hayes, AH. Therapeutic implications of drug interactions with acetaminophen and aspirin. Arch Intern Med 1981;141:301-4.5471 - Woodland C, Verjee Z, Giesbrecht E, et al. The digoxin-propafenone interaction: characterization of a mechanism using renal tubular cell monolayers. J Pharmacol Exp Ther 1997;283:39-45.5822 - Dahan A, Altman H. Food-drug interaction: grapefruit juice augments drug bioavailability-mechanism, extent, and relevance. Eur J Clin Nutr 2004;58:1-9.5853 - Tabloid (thioguanine) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2008 Oct.5879 - Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother 2004;38:50-36114 - Lin JH, Yamazaki M. Role of p-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet 2003;42:59-98.6320 - Schoene NW. Vitamin E and omega-3 fatty acids: effectors of platelet responsiveness. Nutrition 2001;17:793-6.6339 - Iprivask (desirudin) package insert. Hunt Valley, MD: Canyon Pharmaceuticals; 2010 Jan.6359 - Stern SJ, Craig JR, Flock S, et al. Effect of aspirin on photodynamic therapy utilizing chloroaluminum sulfonated phthalocyanine (CASP). Lasers Surg Med 1992;12:494-9. Abstract.6413 - Arixtra (fondaparinux sodium) Injection package insert. West Orange, NJ: Organon Sanofi-Synthelabo LLC; 2004 May.6466 - Remick SC, Grem JL, Fischer PH, et al. Phase I trial of 5-fluorouracil and dipyridamole administered by seventy-two-hour concurrent continuous infusion. Cancer Res 1990;50:2667-72.6625 - Photofrin (porfimer) package insert. Birmingham, AL: Axcan Scandipharm Inc.; 2003 Aug.6880 - Thrombate III (antithrombin III) package insert. Elkhart, IN: Bayer Corporation; 2016 Feb.6886 - Strauss R, Wehler M, Mehler K, et al. Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements, and outcome. Crit Care Med 2002;30:1765-71.7299 - Lovaza (omega-3 acid ethyl esters, also known as fish oil, omega-3 fatty acids) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2008 Jun.7537 - Ventavis (iloprost) package insert. Titusville, NJ: Actelion Pharmaceuticals US, Inc.; 2022 Mar.7557 - Clolar (clofarabine) package insert. Cambridge, MA: Genzyme Corporation; 2010 Dec.8493 - Arranon (nelarabine) package insert. Research Triangle Park, NC: GlaxoSmithKline: October 2005.11307 - Riffkin CD, Chung R, Wall DM, et al. Modulation of the function of human MDR1 P-glycoprotein by the antimalarial drug mefloquine. Biochem Pharmacol 1996;52:1545-52.11309 - Lin JH. Drug-drug interaction mediated by inhibition and induction of P-glycoprotein. Adv Drug Deliv Rev 2003;55:53-81.11322 - Sansone-Parsons A, Krishna G, Simon J, et al. Effects of age, gender, and race/ethnicity on the pharmacokinetics of posaconazole in healthy volunteers. Antimicrob Agents Chemother 2007;51:495-502.22005 - Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol 2006;61(3):246-255.23431 - Savella (milnacipran hydrochloride) tablets package insert. Madison, NJ: Allergan USA, Inc.; 2022 Dec.25082 - Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med 1997;336:1108.25083 - Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology 1996;46:1775-6.25273 - Lamant V, Mauco G, Braquet P, et al. Inhibition of the metabolism of platelet activating factor (PAF-acether) by three specific antagonists from Ginkgo biloba. Bio Pharmacol 1987;36:2749-52.25588 - Ariga T. Platelet aggregation inhibitor in garlic (letter). Lancet 1980;i:150.26011 - Lanza FL. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol 1998;93:2037-2046.27253 - Meeks ML, Mahaffey KW, Katz MD. Danazol increases the anticoagulant effect of warfarin. Ann Pharmacother 1992;26:641-2.27670 - White HD, Aylward PE, Frey MJ, et al. Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Circulation 1997;96:2155-61.27671 - White H; Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial Investigators. Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial. Lancet 2001;358:1855-63.27672 - Lincoff AM, Bittl JA, Harrington RA, et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA 2003;289:853-63.27983 - Sporanox (itraconazole) capsules package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2022 Dec.28003 - Mifeprex (Mifepristone, RU-486) package insert. New York, NY: Danco Laboratories, LLC.; 2023 Mar.28040 - Xanax (alprazolam tablet) package insert. New York, NY: Pharmacia & Upjohn Company; 2023 Jan.28158 - VFEND (voriconazole) tablets, suspension, and injection package insert. New York, NY: Pfizer Inc; 2022 Oct.28193 - Viread (tenofovir disoproxil fumarate) package insert. Foster City, CA: Gilead Sciences, Inc; 2019 Apr.28238 - Biaxin (clarithromycin) package insert. North Chicago, IL: AbbVie, Inc.; 2019 Sep.28260 - Paxil (paroxetine) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Seot.28275 - Effexor (venlafaxine) package insert. Philadelphia, PA: Wyeth Pharmaceuticals, Inc.; 2021 Sept.28315 - Norvir (ritonavir capsules) package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.28343 - Zoloft (sertraline) package insert. Morgantown, WV: Viatris Specialty LLC; 2023 Jan.28434 - Wodlinger AM, Pieper JA. The role of clopidogrel in the management of acute coronary syndromes. Clin Ther 2003;25:2155-81.28435 - Plavix (clopidogrel) package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2022 Sept28436 - Ticlid (ticlopidine) package insert. Nutley, NJ: Roche Laboratories, Inc.; 2005 Dec.28442 - Sustiva (efavirenz) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2019 Oct.28470 - Vaes LP, Chyka PA. Interactions of warfarin with garlic, ginger, ginkgo, or ginseng: nature of the evidence. Review. Ann Pharmacother 2000;34:1478-82.28476 - Rescriptor (delavirdine) package insert. Research Triangle Park, NC: ViiV Healthcare; 2019 Aug.28535 - Cerebyx (fosphenytoin sodium) package insert. New York, NY: Pfizer Labs; 2022 Apr.28549 - Coumadin (warfarin tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2017 Aug.28610 - Rapamune (sirolimus) package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2021 Jun.28723 - Refludan (lepirudin) package insert. Wayne, NJ: Bayer HealthCare Pharmaceuticals, Inc.; 2006 Dec.28843 - Zonegran (zonisamide) package insert. Dublin, Ireland: Concordia Pharmaceuticals, Inc.; 2020 Apr.28995 - Invirase (saquinavir) package insert. South San Francisco, CA: Genentech Inc.; 2020 Sept.29012 - Lexiva (fosamprenavir calcium) package insert. Research Triangle Park, NC: ViiV Healthcare; 2019 Mar29088 - Sular (nisoldipine) package insert. Atlanta, GA: Shionogi Pharma, Inc.; 2017 Jun.29289 - Xifaxan (rifaximin) package insert. Bridgewater, NJ: Salix Pharmaceuticals, Inc.; 2022 Oct.29472 - Oncovin (vincristine sulfate injection, USP) package insert. Indianapolis, IN: Eli Lilly and Company; 1997 Oct.29575 - Trental (pentoxifylline) package insert. Bridgewater, NJ: Sanofi-Aventis Pharmaceuticals Inc.; 2010 Jun.29579 - Schoene NW. Vitamin E and omega-3 fatty acids: effectors of platelet responsiveness. Nutrition 2001;17:793-6.29586 - Angiomax (bivalirudin) for injection package insert. Parsippany, NJ: The Medicines Company; 2019 Jun.29732 - Lovenox (enoxaparin) injection package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2021 Dec29816 - ReoPro (abciximab injection) package insert. Horsham, PA: Janssen Biotech Inc.; 2019 Aug.29934 - Cymbalta (duloxetine hydrochloride) delayed-release capsules package insert. Indianapolis, IN: Eli Lilly and Company; 2021 Sept.30003 - Visudyne (verteporfin for injection) package insert. Bridgewater, NJ: Bausch Health US, LLC.; 2021 Jul.30054 - Prastera Kit (prasterone 200 mg softgels, supplied in a convenience package with ibuprofen oral tablets 400mg) package insert. Moristown NJ; Health Science Funding LLC: 2014 April.30141 - Integrilin (eptifibatide) package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2021 Feb.30142 - Aggrastat (tirofiban) package insert. Princeton, NJ: Medicure Pharma; 2019 May.30163 - Agrylin (anagrelide) capsules package insert. Lexington, MA: Takeda Pharmaceuticals USA, Inc.; 2021 Oct.30210 - Remodulin (treprostinil sodium injection) package insert. Research Triangle Park, NC: United Therapeutics Corp.; 2021 Feb.30282 - Synalgos-DC (aspirin; caffeine; dihydrocodeine) capsules package insert. Atlanta, GA: Mikart, Inc.; 2019 Oct.30314 - Rifadin capsules and injection (rifampin) package insert. Bridgewater, NJ: Sanofi-Aventis, LLC; 2021 Dec.30431 - Marinol (dronabinol, THC) package insert. Marietta, GA: Unimed Pharmaceuticals, Inc.; 2023 Jan.30676 - Emend (aprepitant oral products) package insert. Whitehouse Station, NJ: Merck & Co.,Inc.; 2019 Nov.30966 - Sufenta (sufentanil citrate injection) package insert. Lake Forest, IL: Akorn Pharmaceuticals, Inc.; 2019 Oct31320 - Aptivus (tipranavir) package insert. Ridgefield, CT: Boehringer Ingelheim; 2020 Jun.31764 - Vaprisol (conivaptan hydrochloride injection) package insert. Deerfield, IL: Baxter Healthcare Corporation; 2016 Oct.31832 - Nexavar (sorafenib) package insert. Wayne, NJ; Bayer HealthCare Pharmaceuticals Inc.; 2020 July.32432 - Prezista (darunavir) package insert. Horsham, PA: Janssen Products, LP; 2023 Mar.32789 - Zolinza (vorinostat) capsules package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2018 Dec.32857 - Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb.32984 - Kim LS, Axelrod LJ, Howard P, et al. Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Ostearthritis Cartilage 2006;14:286-94.32986 - Roberts AJ, O'Brien ME, Subak-Sharpe G. Nutraceuticals: The Complete Encyclopedia of Supplements, Herbs, Vitamins, and Healing Foods. New York, New York: The Berkley Publishing Group; 2001.33192 - Tykerb (lapatinib) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2018 Dec.33473 - Selzentry (maraviroc) package insert. Research Triangle Park, NC: ViiV Healthcare; 2020 Oct.33536 - Hycamtin (topotecan) capsules package insert. Research Triangle Park, NC: GlaxoSmithKline; 2018 Sept.33578 - Kruijtzer CMF, Beijnen JH, Rosing H, et al. Increased oral bioavailability of topotecanin combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J Clin Oncol 2002;20:2943-50.33607 - Loperamide hydrochloride capsules package insert. Morgantown, WV: Mylan Pharmaceuticals Inc; 2016 Oct.33653 - Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357:2666-76.33718 - Intelence (etravirine) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 July.34329 - Eberl S, Renner B, Neubert A, et al. Role of p-glycoprotein inhibition for drug interactions: evidence from in vitro and pharmacoepidemiological studies. Clin Pharmacokinet 2007;46:1039-49.34331 - Wang RB, Kuo KL, Lien LL, et al. Structure-activity relationship: analyses of p-glycoprotein substrates and inhibitors. J Clin Pharm Ther 2003;28:203-228.34332 - Eriksson UG, Dorani H, Karlsson J, et al. Influence of erythromycin on the pharmacokinetics of ximelagatran may involve inhibition of P-glycoprotein-mediated excretion. Drug Metab Dispos 2006;34:775-82.34512 - Saitoha H, Saikachia Y, Kobayashia M, et al. Limited interaction between tacrolimus and P-glycoprotein in the rat small intestine. Eur J Pharm Sci 2006;28:34-42.36055 - Effient (prasugrel) package insert. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2020 Dec.36101 - Multaq (dronedarone) package insert. Bridgewater, NJ: Sanofi-aventis U.S. LLC; 2020 Nov.37590 - Elewski B, Tavakkol A. Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality. Ther Clin Risk Manag. 2005;1(4):299-306.38831 - Oleptro (trazodone hydrochloride) extended-release tablets package insert. Dublin, Ireland: Labopharm Europe Limited; 2014 Jul.38955 - Xiaflex (collagenase clostridium histolyticum) package insert. Malvern, PA: Endo Pharmaceuticals, Inc.; 2022 Aug.40027 - Emend (fosaprepitant dimeglumine injection) package insert. Whitehouse Station, NJ: Merck & Co.,Inc.; 2022 May.40043 - Elmiron (pentosan) capsule package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Feb.40233 - Sporanox (itraconazole) oral solution package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2022 Dec.41251 - Bone KM: Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence. Mol Nutr Food Res 2008;52(7):764-771.41258 - Aruna LL, Naidu MU. Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects. Br J Clin Pharmacol 2006;63:333-338.41265 - Engelsen J, Nielsen JD, Winter K. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treated outpatients; a randomised, double blind, placebo-crossover trial. Thromb Haemost 2002;87:1075-6.41543 - Halcion (triazolam) package insert. New York, NY: Pharmacia and Upjohn Company; 2023 Jan.41826 - Zevalin (ibritumomab tiuxetan) package insert. Irvine, CA: Spectrum Pharmaceuticals, Inc.; 2019 Sept.41851 - Thymoglobulin (anti-thymocyte globulin (rabbit)) package insert. Cambridge, MA: Genzyme Corporation; 2018 Sept.41934 - Lysodren (mitotane) package insert. Princeton, NJ: Bristol-Myers Squibb Oncology; 2021 June.42121 - Pradaxa (dabigatran) oral capsules package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2021 Jun.43177 - Viibryd (vilazodone) tablets package insert. Madison, NJ; Allergan USA, Inc.: 2021 July.43880 - Lamisil (terbinafine oral granules) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019 Mar.43881 - Terbinafine tablets package insert. Princeton, NJ: Bionpharma Inc.; 2021 Nov.44854 - Xarelto (rivaroxaban) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2023 Feb.44951 - Brilinta (ticagrelor) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 May.45290 - Complera (emtricitabine; rilpivirine; tenofovir disoproxil fumarate) package insert. Foster City, CA: Gilead Sciences, Inc.; 2019 Nov.45335 - Zelboraf (vemurafenib) tablet package insert. South San Francisco, CA: Genentech USA, Inc.; 2020 May.45458 - Xalkori (crizotinib) package insert. New York, NY: Pfizer Labs; 2022 July.46322 - Hycamtin (topotecan hydrochloride) for Injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2018 Sept.47165 - Norvir (ritonavir tablets, solution, and powder) package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.48524 - Kalydeco (ivacaftor) package insert. Boston, MA: Vertex Pharmaceuticals Incorporated; 2023 May.48620 - Pletal (cilostazol) package insert. Rockville, MD: Otsuka America Pharmaceutical, Inc.; 2017 May.48697 - Korlym (mifepristone) tablet package insert. Menlo Park, CA: Corcept Therapeutics; 2019 Nov.49451 - Drayson MT, Chapman CE, Dunn JA, et al. MRC trial of alpha2b-interferon maintenance therapy in first plateau phase of multiple myeloma. MRC Working Party on Leukaemia in Adults. Br J Haematol 1998;101(1):195-202.49823 - Afinitor (everolimus) tablets package insert. East Hanover, NJ:Novartis Pharmaceuticals Corporation; 2022 Feb.49866 - Stendra (avanafil) package insert. Freehold, NJ: Metuchen Pharmaceuticals, LLC.; 2022 Oct.49903 - Zortress (everolimus) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2018 Aug.49946 - Fragmin (dalteparin) injection. New York, NY: Pfizer, Inc.; 2020 Dec.50586 - Torisel (temsirolimus) injection package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc; 2018 March.50617 - Dabigatran (Pradaxa) European package insert. Boehringer Ingelheim International GmbH; Germany: 2012 Mar.51727 - Xtandi (enzalutamide) capsule and tablet package insert. Northbrook, IL:Astellas Pharma US, Inc.; 2022 Sept.51834 - Food and Drug Administration (FDA): Drug development and drug interactions. Retrieved Sep 19, 2012. Available on the World Wide Web http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#transporter.52351 - Dilantin (phenytoin sodium) oral suspension package insert. New York, NY: Parke-Davis Division of Pfizer Inc; 2022 Mar.52498 - Parasrampuria DA, Lantz MV, Benet LZ. A Human Lymphocyte Based Ex Vivo Assay to Study the Effect of Drugs on P-Glycoprotein (P-gp) Function. Pharm Res 2001;18(1):39-44.52506 - Cometriq (Cabozantinib) capsules package insert. South San Francisco, CA:Exelixis, Inc.; 2020 Jan52698 - Juxtapid (lomitapide) package insert. Cambridge, MA: Aegerion Pharmaceuticals, Inc.; 2019 Dec.52739 - Eliquis (apixaban) package insert. Bristol-Myers Squibb Company; Princeton, NJ. 2021 Apr.53295 - Ado-trastuzumab emtansine (Kadcyla) Package Insert. San Francisco, CA: Genentech, Inc; 2022 Feb.54802 - Tafinlar (dabrafenib) capsules package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2023 Mar.55469 - Fetzima (levomilnacipran) extended-release capsules package insert. North Chicago, IL: AbbVie, Inc.; 2023 Mar.56041 - Trintellix (vortioxetine tablets) package insert. Lexington, MA: Takeda Pharmaceuticals America, Inc.; 2021 Sept.56353 - Gazyva (obinutuzumab) injection package insert. South San Francisco, CA: Genentech, Inc.; 2022 July.56410 - Imbruvica (ibrutinib) capsules, tablets, and oral suspension package insert. Sunnyvale, CA: Pharmacyclics, Inc.; 2023 May.56471 - Olysio (simeprevir) capsule package insert. Titusville, NJ: Janssen Therapeutics; 2017 Nov.56538 - Vickers AE, Sinclair JR, Zollinger M. Multiple cytochrome P-450s involved in the metabolism of terbinafine suggest a limited potential for drug-drug interactions. Drug Metab Dispos. 1999;27(9):1029-1038.56565 - Wessler JD, Grip LT, Mendell J, et al. The P-glycoprotein transport system and cardiovascular drugs. J Am Coll Cardiol 2013;61:2495-502.56579 - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Updated Mar 10, 2020. Retrieved from the World Wide Web at www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm56871 - Navelbine (vinorelbine) injection package insert. Parsippany, NJ: Pierre Fabre Pharmaceuticals Inc; 2020 Jan.56982 - Argatroban injection package insert. Eatontown, NJ: Hikma Pharmaceuticals USA Inc.; 2020 Jan.57046 - Perucca E, Hedges A, Makki KA, et al. A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. Br J Clin Pharmacol 1984;18:401-10.57048 - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Retrieved from the World Wide Web December 27, 2013. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#major57094 - Zykadia (ceritinib) package insert. Indianapolis, IN: Novartis; 2021 Oct.57151 - Zontivity (vorapaxar) package insert. Parsippany, NJ: Aralez Pharmaceuticals US Inc.; 2019 Nov.57202 - Zhou S, Chan E, Pan S, et al. Pharmacokinetic interactions of drugs with St John's wort. J Psychopharmacol 2004;18:262-76.57675 - Zydelig (idelalisib) tablet package insert. Foster City, CA:Gilead Sciences, Inc.; 2022 Feb.57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.57852 - Dostalek M, Pistovcakova J, Jurica J, et al. The effect of St John's wort (hypericum perforatum) on cytochrome p450 1a2 activity in perfused rat liver. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2011;155:253-7.58000 - Tybost (cobicistat) package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Sept.58167 - Harvoni (ledipasvir; sofosbuvir) tablet and oral pellets package insert. Foster City, CA: Gilead Sciences, Inc; 2020 Mar.58171 - Akynzeo (fosnetupitant; palonosetron injection and netupitant; palonosetron capsules) package insert. Lugano, Switzerland: Helsinn Healthcare; 2023 February.58203 - Ofev (nintedanib) capsule package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2022 Jan.58220 - Bachmakov I, Werner U, Endress B, et al. Characterization of beta-adrenoceptor antagonists as substrates and inhibitors of the drug transporter P-glycoprotein. Fundam Clin Pharmacol 2006;20:273-82.58664 - Viekira Pak (ombitasvir; paritaprevir; ritonavir; dasabuvir) tablet package insert. North Chicago, IL: AbbVie, Inc; 2019 Dec.58685 - Savaysa (edoxaban) package insert. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2021 Apr.59042 - Cresemba (isavuconazonium) package insert. Northbrook, IL: Astellas Pharma US, Inc; 2022 Feb.59891 - Orkambi (lumacaftor; ivacaftor) tablet package insert. Boston, MA: Vertex Pharmaceuticals, Inc. 2022 Sept60001 - Daklinza (daclatasvir) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2019 Oct.60002 - Technivie (ombitasvir; paritaprevir; ritonavir) tablet package insert. North Chicago, IL: AbbVie, Inc; 2019 Dec.60087 - Sprycel (dasatinib) tablet package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2023 Feb.60099 - Addyi (flibanserin tablets) package insert. Raleigh, NC: Sprout Pharmaceuticals, Inc.; 2021 Sept.60281 - Cotellic (cobimetinib) tablets package insert. San Francisco, CA: Genentech USA, Inc; 2022 Oct.60297 - Tagrisso (osimertinib) tablet package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022 Oct.60523 - Zepatier (elbasvir; grazoprevir) tablet package insert. Whitehouse Station, NJ: Merck, Inc; 2021 Dec.60681 - Defitelio (defibrotide sodium) injection package insert. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; 2016 Mar.60706 - Venclexa (venetoclax) tabs package insert. South San Francisco, CA: Genentech, Inc.; 2020 Nov.60738 - Cabometyx (Cabozantinib) tablets package insert. Alameda, CA: Exelixis, Inc.; 2022 July.60911 - Epclusa (sofosbuvir; velpatasvir) tablet and oral pellets package insert. Foster City, CA: Gilead Sciences, Inc; 2022 Apr.60951 - Syndros (dronabinol) oral solution package insert. Chandler, AZ; Insys Therapeutics, Inc. 2022 Sept.61360 - Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease. J Am Coll Cardiol 2016;68(10):1082-1115.61413 - Vemlidy (tenofovir alafenamide) package insert. Foster City, CA: Gilead Sciences, Inc.; 2022 Oct.61816 - Kisqali (ribociclib) tablets package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2022 Oct.61909 - Alunbrig (brigatinib) tablet package insert. Cambridge, MA: Ariad Pharmaceuticals Inc.; 2022 March.62037 - Bevyxxa (betrixaban) capsules package insert. South San Francisco, Ca: Portola Pharmaceuticals, Inc.; 2020 Aug.62127 - Nerlynx (neratinib) package insert. Los Angeles, CA: Puma Biotechnology, Inc; 2021 June.62131 - Vosevi (sofosbuvir; velpatasvir; voxilaprevir) tablet package insert. Foster City, CA: Gilead Sciences, Inc; 2019 Nov.62181 - Idhifa (enasidenib) tablet package insert. Summit, NJ: Celgene Corporation; 2020 Nov.62201 - Mavyret (glecaprevir; pibrentasvir) tablets package insert. North Chicago, IL: AbbVie Inc.; 2021 Sept.62611 - Prevymis (letermovir) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2020 Mar.62874 - Erleada (apalutamide) tablets package insert. Horsham, PA: Janssen Products, LP; 2023 Feb.62889 - Apadaz (benzhydrocodone; acetaminophen) tablets package insert. Newton, PA: KVK-Tech, Inc.; 2021 Mar.63043 - Tattelman E. Health effects of garlic. Am Fam Physician. 2005;72:103-106. Review.63084 - Tavalisse (fostamatinib disodium hexahydrate) tablets package insert. South San Francisco, CA: Rigel Pharmaceuticals, Inc.; 2018 Apr.63309 - Epidiolex (cannabidiol) oral solution package insert. Carlsbad, CA: Greenwich Biosciences, Inc.; 2022 Feb.63317 - Braftovi (encorafenib) capsules package insert. Boulder, CO: Array BioPharma Inc.; 2022 Feb.63368 - Tibsovo (ivosidenib) tablet package insert. Cambridge, MA: Agios Pharmaceuticals; 2022 May.63456 - Diacomit (stiripentol) package insert. Beauvais, France: Biocodex; 2022 Jul.63571 - Copiktra (duvelisib) capsules package insert. Las Vegas, NV: Secura Bio, Inc.; 2021 Dec.63624 - Tegsedi (inotersen) injection package insert. Waltham, MA: Akcea Therapeutics, Inc.; 2022 Jun.63651 - Talzenna (talazoparib) capsules package insert. New York, NY: Pfizer Labs; 2021 Sept.63731 - Dsuvia (sufentanil) sublingual tablets package insert. Redwood City, CA: AcelRx Pharmaceuticals, Inc.; 2019 Oct.63787 - Xospata (gilteritinib) tablets package insert. Northbrook, IL: Astellas Pharma US, Inc.; 2022 Jan.63940 - Cablivi (caplacizumab-yhdp) injection package insert. Cambridge, MA: Ablynx US; 2022 Feb.64561 - Pretomanid tablet package insert. Hyderabad, India: Mylan, Laboratories Limited; 2022 Dec.64568 - Inrebic (fedratinib) capsules package insert. Summit, NJ: Celgene Corporation; 2021 Dec.64576 - Xenleta (lefamulin) package insert. Dublin, Ireland: Nabriva Therapeutics US, Inc.; 2021 Mar.64590 - Nourianz (istradefylline) tablets package insert. Bedminster, NJ: Kyowa Kirin, Inc.; 2019 Aug.64685 - Reyvow (lasmiditan) tablets package insert. Indianapolis, IN: Eli Lilly and Company; 2022 Sep.64778 - Oxbryta (voxelotor) tablets package insert. South San Francisco, CA: Global Blood Therapeutics, Inc.; 2021 Dec.64870 - Dayvigo (lemborexant) tablets package insert. Nutley, NJ: Eisai Inc.; 2023 Apr.64874 - Ubrelvy (ubrogepant) tablets package insert. Madison, NJ: Allergan USA, Inc.; 2023 Feb.65052 - Nurtec ODT (rimegepant) orally disintegrating tablet package insert. New Haven, CT: Biohaven Pharmaceuticals, Inc.; 2022 Apr.65246 - Koselugo (selumetinib) capsules package insert. Wilmington, DE: AstraZeneca Pharmaceuticals, LP; 2021 Dec.65295 - Tukysa (tucatinib) tablets package insert. Bothell, WA: Seattle Genetics, Inc.; 2023 Jan65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed April 20, 2023. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.65377 - Tabrecta (capmatinib) tablets package insert. Novartis Pharmaceuticals Corporation;East Hanover, NJ:2023 March.65387 - Retevmo (selpercatinib) capsules package insert. Indianapolis, IN: Eli Lilly and Company; 2022 Sept.65685 - Dooley KE, Bliven-Sizemore EE, Weiner M, et al. Safety and pharmacokinetics of escalating daily doses of the antituberculosis drug rifapentine in healthy volunteers. Clin Pharmacol Ther 2012; 91:566129 - Zokinvy (lonafarnib) capsules package insert. Palo Alto, CA: Eiger BioPharmaceuticals, Inc.; 2020 Nov.66159 - Orladeyo (berotralstat) package insert. Durham, NC; BioCryst Pharmaceuticals, Inc.: 2022 Mar.66183 - Orgovyx (relugolix) tablets package insert. Brisbane, CA: Myovant Sciences, Inc.; 2023 Mar.66336 - Lupkynis (voclosporin) capsules package insert. Rockville, MD: Aurinia Pharma U.S., Inc.; 2021 Jan.66372 - Tepmetko (Tepotinib) tablets package insert. Rockland, MA:EMD Serono, Inc; 2023 Mar.66700 - Lumakras (sotorasib) tablet package insert. Thousand Oaks, CA: Amgen, Inc.; 2023 Apr.66793 - Kerendia (finerenone) tablets package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2022 Sept.67136 - Fyarro (sirolimus protein-bound particles) injectable suspension package insert. Pacific Palisades, CA: Aadi Bioscience, Inc.; 2021 Nov.67137 - Livtencity (maribavir) package insert. Lexington, MA: Takeda Pharmaceuticals America, Inc.; 2023 Apr.67277 - Cibinqo (abrocitinib) package insert. New York, NY: Pfizer; 2023 Feb.67403 - Pyrukynd (mitapivat) tablets package insert.Cambridge, MA: Agios Pharmaceuticals, Inc.; 2022 Feb.67427 - Vonjo (pacritinib) capsules package insert. Seattle, WA: CTI BioPharma Corp; 2022 Feb.68007 - Relyvrio (sodium phenylbutyrate and taurursodiol) oral suspension package insert. Cambridge, MA: Amylyx Pharmaceuticals, Inc., 2022 Sep.68013 - Lytgobi (futibatinib) tablets package insert. Princeton, NJ: Taiho Oncology, Inc.; 2022 Sept.68325 - Krazati (adagrasib) tablets package insert. San Diego, CA: Mirati Therapeutics, Inc.; 2022 Dec.68383 - Sunlenca (lenacapavir) package insert. Foster City, CA: Gilead Science, Inc.; 2022 Dec.68520 - Jaypirca (pirtobrutinib) tablets package insert. Indianapolis, IN: Lilly USA, LLC; 2023 Jan.68530 - Orserdu (elacestrant) tablets package insert. New York, NY; Stemline Therapeutics, Inc: 2023 Jan.68641 - Sparsentan (Filspari) package insert. San Diego, CA: Travere Therapeutics, Inc.; 2023 Feb.

      Monitoring Parameters

      • CBC
      • LFTs

      US Drug Names

      • BRILINTA
      ;