Ticagrelor interactions

…(Childs-Pugh categories B and C), since alfuzosin blood levels are increased in these patients [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ]. with potent CYP3A4 inhibitors such as ketoconazole, itraconazole, and ritonavir, since alfuzosin blood levels are increased [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . in… (Alfuzosin label, Contraindications)

• taking strong cytochrome P450 3A (CYP3A) inhibitors (e.g., ketoconazole, itraconazole), except ritonavir [see Dosage and Administration (2.5) , Warnings and Precautions (5.5) , Drug Interactions (7.1) ] . (Alprazolam label, Contraindications)

…hematomas in these patients include: • use of indwelling epidural catheters • concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants • a history of traumatic or repeated epidural or spinal punctures • a history of spinal deformity or spinal surgery • optimal timing between… (Apixaban label, Boxed warning)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

WARNING: BLEEDING RISK • BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding ( 5.1 , 6.1 ). (Ticagrelor label, Boxed warning)

WARNING: BLEEDING RISK • BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding ( 5.1 , 6.1 ). (Ticagrelor label, Boxed warning)

Do not use avanafil in patients taking strong CYP3A4 inhibitors [see Warnings and Precautions ( 5.2 ) and Dosage and Administration ( 2.3 )]. (Avanafil label, Drug interactions)

Concomitant administration of BIXLENVO with combined P-gp, UGT1A1, and strong CYP3A inhibitors is not recommended. (Bictegravir, emtricitabine, and tenofovir alafenamide label, Drug interactions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

Evaluate patients starting CYP3A4 inhibitors or stopping CYP3A4 inducers at frequent intervals for respiratory depression. (Buprenorphine label, Drug interactions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

Celecoxib 100 mg twice daily was non-inferior to naproxen 375 to 500 mg twice daily and ibuprofen 600 to 800 mg three times daily for the composite endpoint of the Antiplatelet Trialists' Collaboration (APTC), which consists of cardiovascular death (including hemorrhagic death), non-fatal myocardial infarction, and non-fatal stroke [ see Clinical Studies (14.5)… (Celecoxib label, Warnings and precautions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

WARNING: BLEEDING RISK • BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding ( 5.1 , 6.1 ). (Ticagrelor label, Boxed warning)

Avoid use of strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin) [see Clinical Pharmacology (12.3) ] . (Ticagrelor label, Drug interactions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

WARNING: BLEEDING RISK • BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding ( 5.1 , 6.1 ). (Ticagrelor label, Boxed warning)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (Codeine label, Boxed warning)

Patients with renal or hepatic impairment should not be given colchicine capsules with drugs that inhibit both P-glycoprotein and CYP3A4 inhibitors [see Drug Interactions (7) ] . (Colchicine label, Contraindications)

…hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the… (Dabigatran label, Boxed warning)

Strong CYP3A4 inhibitors: Avoid concomitant use. (Daridorexant label, Drug interactions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION WITH POTENT CYP3A4 INHIBITORS Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics. (Dihydroergotamine label, Boxed warning)

WARNING: BLEEDING RISK • BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding ( 5.1 , 6.1 ). (Ticagrelor label, Boxed warning)

Drug-Drug Interactions Strong Inhibitors of Cytochrome P450 (CYP) 3A4 Tamsulosin-containing products, including JALYN, should not be coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole) as this can significantly increase tamsulosin exposure [see Drug Interactions (7.1) , Clinical Pharmacology (12.3) ]. (Dutasteride and tamsulosin label, Warnings and precautions)

…hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the… (Edoxaban label, Boxed warning)

• Recent use (i.e., within at least 72 hours) of the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, or nelfinavir [see Drug Interactions (7.2) and Clinical Pharmacology (12.3) ]. (Eletriptan label, Contraindications)

…hematomas in these patients include: Use of indwelling epidural catheters Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, and other anticoagulants A history of traumatic or repeated epidural or spinal punctures A history of spinal deformity or spinal surgery Optimal timing between… (Enoxaparin label, Boxed warning)

…Patients Eplerenone is contraindicated in all patients with: • serum potassium > 5.5 mEq/L at initiation, • creatinine clearance ≤ 30 mL/min, or • concomitant administration of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir) [see Drug Interactions (7.1) , Clinical Pharmacology (12.3)… (Eplerenone label, Contraindications)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

Avoid simvastatin and lovastatin doses greater than 40 mg [ see Clinical Pharmacology (12.3) ]. (Ticagrelor label, Drug interactions)

• Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of fentanyl. (Fentanyl label, Boxed warning)

CYP3A4 Inhibitors Doses of Toviaz greater than 4 mg are not recommended in adult patients taking strong CYP3A4 inhibitors, such as ketoconazole, itraconazole, and clarithromycin [see Dosage and Administration (2.5) ]. (Fesoterodine label, Drug interactions)

Contraindicated with Strong or Moderate CYP3A4 Inhibitors The concomitant use of ADDYI and moderate or strong CYP3A4 inhibitors increases flibanserin concentrations, which can cause severe hypotension and syncope [see Warnings and Precautions (5.2) ] . (Flibanserin label, Boxed warning)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (Fluticasone label, Drug interactions)

Avoid strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): May increase risk of systemic corticosteroid and cardiovascular effects. (Fluticasone and salmeterol label, Drug interactions)

…in these patients include: • use of indwelling epidural catheters • concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants • a history of traumatic or repeated epidural or spinal puncture • a history of spinal deformity or spinal surgery • Optimal timing between… (Fondaparinux label, Boxed warning)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

Cytochrome P450 3A4 Interaction The concomitant use of hydrocodone bitartrate and acetaminophen tablets with all Cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (Hydrocodone and acetaminophen label, Boxed warning)

Avoid use of strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin) [see Clinical Pharmacology (12.3) ] . (Ticagrelor label, Drug interactions)

…bradycardia [see Warnings and Precautions ( 5.3 )] • Severe hepatic impairment [see Use in Specific Populations ( 8.6 )] • Pacemaker dependence (heart rate maintained exclusively by the pacemaker) [see Drug Interactions ( 7.3 )] • Concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors [see Drug Interactions ( 7.1 )] Acute decompensated heart failure ( 4 ) (Ivabradine label, Contraindications)

Avoid use of strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin) [see Clinical Pharmacology (12.3) ] . (Ticagrelor label, Drug interactions)

Strong or moderate CYP3A inhibitors: Avoid concomitant use. (Lemborexant label, Drug interactions)

Avoid simvastatin and lovastatin doses greater than 40 mg [ see Clinical Pharmacology (12.3) ]. (Ticagrelor label, Drug interactions)

Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) [see Drug Interactions ( 7.1 )]. (Lurasidone label, Contraindications)

Strong CYP3A4 inhibitors (ketoconazole, ritonavir) increase exposure to macitentan: avoid co-administration with OPSUMIT ( 7.2 , 12.3 ) . (Macitentan label, Drug interactions)

Cytochrome P450 3A4 Interaction The concomitant use of DEMEROL Injection with all cytochrome P450 3A4 inhibitors may result in an increase in meperidine plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (Meperidine label, Boxed warning)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

Avoid use of strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin) [see Clinical Pharmacology (12.3) ] . (Ticagrelor label, Drug interactions)

CYP3A4 inhibitors and inducers : SULAR is substrate of CYP3A4 and coadministration of SULAR with any known inducer or inhibitor of CYP3A4 should be avoided in general. (Nisoldipine label, Drug interactions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

Cytochrome P450 3A4 Interaction The concomitant use of Oxycodone Hydrochloride Oral Solution with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (Oxycodone label, Boxed warning)

Cytochrome P450 3A4 Interaction The concomitant use of oxycodone hydrochloride tablets with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (Oxycodone and acetaminophen label, Boxed warning)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

WARNING: BLEEDING RISK • BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding ( 5.1 , 6.1 ). (Ticagrelor label, Boxed warning)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

• Avoid simultaneous use of propafenone with both a cytochrome P450 2D6 (CYP2D6) inhibitor and a 3A4 inhibitor (CYP3A4). (Propafenone label, Warnings and precautions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

• Strong CYP3A4 Inhibitors: Avoid concomitant administration. (Rimegepant label, Drug interactions)

Avoid use of strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin) [see Clinical Pharmacology (12.3) ] . (Ticagrelor label, Drug interactions)

…in these patients include: • use of indwelling epidural catheters • concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants • a history of traumatic or repeated epidural or spinal punctures • a history of spinal deformity or spinal surgery • optimal timing between… (Rivaroxaban label, Boxed warning)

• Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (Salmeterol label, Drug interactions)

Avoid simvastatin and lovastatin doses greater than 40 mg [ see Clinical Pharmacology (12.3) ]. (Ticagrelor label, Drug interactions)

Interaction with Strong Inhibitors and Inducers of CYP3A4 and/or P-gp Avoid concomitant use of sirolimus with strong inhibitors of CYP3A4 and/or P-gp (such as ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin) or strong inducers of CYP3A4 and/or P-gp (such as rifampin or rifabutin) [ see Drug Interactions (7.2) ]. (Sirolimus label, Warnings and precautions)

The dosage of Solifenacin succinate tablets greater than 5 mg once daily is not recommended when concomitantly used with strong CYP3A4 inhibitors [see Dosage and Administration ( 2.4 )] . (Solifenacin label, Drug interactions)

• Should not be used in combination with strong inhibitors of CYP3A4. (Tamsulosin label, Warnings and precautions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. (Tramadol label, Boxed warning)

The use of RALDESY Should be avoided in patients with known QT prolongation or in combination with other drugs that are inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, voriconazole), or known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotic… (Trazodone label, Warnings and precautions)

• Strong CYP3A Inhibitors and Inducers: Avoid coadministration with strong CYP3A inhibitors and inducers. (Tretinoin label, Drug interactions)

Strong CYP 3A Inhibitors Triazolam is contraindicated in patients receiving strong inhibitors of CYP 3A such as ketoconazole, itraconazole, nefazodone, ritonavir, indinavir, nelfinavir, saquinavir, and lopinavir [see Contraindications (4) , Drug Interactions (7.1) ] . (Triazolam label, Warnings and precautions)

UBRELVY is contraindicated: With concomitant use of strong CYP3A4 inhibitors [see Drug Interactions ( 7.1 )] In patients with a history of serious hypersensitivity to ubrogepant or any component of UBRELVY. (Ubrogepant label, Contraindications)

For patients with atopic dermatitis, coadministration of RINVOQ 30 mg once daily with strong CYP3A4 inhibitors is not recommended. (Upadacitinib label, Drug interactions)

Avoid use of strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin) [see Clinical Pharmacology (12.3) ] . (Ticagrelor label, Drug interactions)

CYP3A4 inhibitors: Use with caution in combination due to increased exposure of alosetron. (Alosetron label, Drug interactions)

Impact of Other Drugs on Amlodipine CYP3A Inhibitors Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (Amlodipine label, Drug interactions)

CYP3A4 Inhibitors : Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (Amlodipine and benazepril label, Drug interactions)

CYP2D6 inhibitors and CYP3A4 Inhibitors : See full prescribing information for ABILIFY MAINTENA dosage modifications when used concomitantly with CYP2D6 inhibitors and/or CYP3A4 inhibitors for greater than 14 days ( 7.1 ) (Aripiprazole label, Drug interactions)

• Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse effects. (Ticagrelor label, Drug interactions)

Strong CYP2D6 REXULTI may be administered without dosage adjustment in patients with MDD when administered with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine). or CYP3A4 inhibitors Administer half of recommended dosage. (Brexpiprazole label, Drug interactions)

Interactions with Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the co-administration of PULMICORT FLEXHALER with ketoconazole, and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) because adverse effects related to… (Budesonide label, Warnings and precautions)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. (Budesonide and formoterol label, Warnings and precautions)

• Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

Other inhibitors and inducers of CYP3A4: Substances that inhibit CYP3A4, such as ketoconazole or ritonavir, may inhibit buspirone metabolism and increase plasma concentrations of buspirone while substances that induce CYP3A4, such as dexamethasone or certain anticonvulsants (phenytoin, phenobarbital, carbamazepine), may increase the rate of buspirone metabolism. (Buspirone label, Drug interactions)

• Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

Clinically Significant Drug Interactions with VRAYLAR Strong or Moderate CYP3A4 Inhibitors Clinical Impact: Concomitant use of VRAYLAR with a strong or moderate CYP3A4 inhibitor increases the exposures of cariprazine and its major active metabolite, didesmethylcariprazine (DDCAR), compared to use of VRAYLAR alone [see Clinical Pharmacology ( 12.3 ) ]. (Cariprazine label, Drug interactions)

Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk. (Citalopram label, Warnings and precautions)

Inhibitors of CYP3A4 and CYP3A5 Inhibitors of CYP3A4 and/or CYP3A5 may increase plasma concentrations of clindamycin [ see Clinical Pharmacology (12.3) ]. (Clindamycin label, Drug interactions)

CYP2D6 and CYP3A4 Inhibitors Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology ( 12.3 )] . (Clozapine label, Drug interactions)

CYP3A4 Inhibitors The systemic exposure of darifenacin from darifenacin extended-release tablets is increased in the presence of CYP3A4 inhibitors. (Darifenacin label, Drug interactions)

• Increased Risk of Bleeding: Concomitant use of aspirin, NSAIDs, other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk ( 5.4 ). (Desvenlafaxine label, Warnings and precautions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of dexlansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . (Dexlansoprazole label, Drug interactions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. (Diclofenac label, Warnings and precautions)

• Monitor digoxin levels with initiation of or any change in BRILINTA. (Ticagrelor label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

…grouped as ACE inhibitors, oral anticoagulants, calcium channel blockers, beta blockers, cardiac glycosides, inducers of CYP3A4, substrates and inhibitors of CYP3A4, substrates and inhibitors of P-glycoprotein, nitrates, sulphonylureas, loop diuretics, potassium sparing diuretics, thiazide diuretics, substrates and inhibitors of tubular organic cation transport,… (Dofetilide label, Drug interactions)

Strong cytochrome P450 (CYP) 3A inhibitors may increase exposure to doxazosin and increased risk of hypotension. (Doxazosin label, Drug interactions)

Monitor for increased dronabinol-related adverse reactions when dronabinol oral solution is co-administered with inhibitors of CYP2C9 (e.g., amiodarone, fluconazole) and inhibitors of CYP3A4 enzymes (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, erythromycin, grapefruit juice). (Dronabinol label, Drug interactions)

Effects of Other Drugs on Dronedarone Ketoconazole and Other Potent CYP3A Inhibitors Concomitant use of ketoconazole as well as other potent CYP3A inhibitors such as itraconazole, voriconazole, ritonavir, clarithromycin, and nefazodone is contraindicated because exposure to dronedarone is significantly increased [see Contraindications (4) , Clinical Pharmacology… (Dronedarone label, Drug interactions)

Consider monitoring serum potassium concentration in high-risk patients who take a strong CYP3A4 inhibitor long-term and concomitantly. (Drospirenone and ethinyl estradiol label, Warnings and precautions)

Concomitant use of antiplatelet drugs and anticoagulants may increase this risk ( 5.5 , 7.4 , 8.1 ) (Duloxetine label, Warnings and precautions)

Concomitant Use with CYP3A Inhibitors Exposure to elexacaftor, tezacaftor and ivacaftor are increased when used concomitantly with strong or moderate CYP3A inhibitors. (Elexacaftor, tezacaftor, and ivacaftor label, Warnings and precautions)

• Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

Coadministration of DESCOVY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of TAF. (Emtricitabine and tenofovir label, Drug interactions)

Increased Risk of Bleeding: Concomitant use of nonsteroidal anti-inflammatory drugs, aspirin, other antiplatelet drugs, warfarin and other anticoagulants may increase risk ( 5.7 , 7) (Escitalopram label, Warnings and precautions)

Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects. (Estradiol label, Drug interactions)

The dose of LUNESTA should be reduced in patients who are administered potent inhibitors of CYP3A4, such as ketoconazole, while taking LUNESTA. (Eszopiclone label, Warnings and precautions)

Inhibitors of P-gp (e.g., digoxin, cyclosporine) may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations. (Everolimus label, Drug interactions)

Coadministration of CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, grapefruit juice, cimetidine) with felodipine may lead to several-fold increases in the plasma levels of felodipine, either due to an increase in bioavailability or due to a decrease in metabolism. (Felodipine label, Drug interactions)

Concentrations of fidaxomicin and OP-1118 may also be decreased at the site of action (i.e., gastrointestinal tract) via P-gp inhibition; however, concomitant P-gp inhibitor use had no attributable effect on safety or treatment outcome of fidaxomicin-treated adult patients in controlled clinical trials. (Fidaxomicin label, Drug interactions)

• Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse effects. (Ticagrelor label, Drug interactions)

Potential Pimozide Interaction Pimozide is metabolized by the cytochrome P4503A4 isoenzyme, and it has been demonstrated that ketoconazole, a potent inhibitor of CYP3A4, blocks the metabolism of this drug, resulting in increased plasma concentrations of parent drug. (Fluvoxamine label, Warnings and precautions)

Ginkgo may increase bleeding risk when taken with anticoagulant or antiplatelet medicines. (NCCIH, Ginkgo)

…Interactions: Effect of other Drugs on INTUNIV Concomitant Drug Name or Drug Class Clinical Rationale and Magnitude of Drug Interaction Clinical Recommendation Strong and moderate CYP3A4 inhibitors, e.g., ketoconazole, fluconazole Guanfacine is primarily metabolized by CYP3A4 and its plasma concentrations can be significantly affected resulting in an increase… (Guanfacine label, Drug interactions)

Platelet Inhibitors Drugs such as acetylsalicylic acid, dextran, phenylbutazone, ibuprofen, indomethacin, dipyridamole, hydroxychloroquine and others that interfere with platelet-aggregation reactions (the main hemostatic defense of heparinized patients) may induce bleeding and should be used with caution in patients receiving heparin sodium. (Heparin label, Drug interactions)

Concomitant administration of inhibitors of CYP3A4 may lead to increases in serum concentrations of ALKINDI SPRINKLE and increase the risk of adverse reactions associated with the use of excessive doses. (Hydrocortisone label, Drug interactions)

• Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

Co-morbid conditions such as coagulation disorder, concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. (Ibuprofen label, Warnings and precautions)

Increased Bleeding Risk with Anticoagulants and Antiplatelet Agents: Some published studies with omega-3 fatty acids have demonstrated prolongation of bleeding time. (Icosapent ethyl label, Drug interactions)

The dose of FANAPT should be reduced in patients co-administered a strong CYP2D6 or CYP3A4 inhibitor. (Iloperidone label, Drug interactions)

Co-morbid conditions, such as coagulation disorders, or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. (Indomethacin label, Warnings and precautions)

Potential for other drugs to affect ivacaftor CYP3A inhibitors: Reduce KALYDECO dosage in patients aged 6 months and older when co-administered with strong CYP3A inhibitors (e.g., ketoconazole) or moderate CYP3A inhibitors (e.g., fluconazole). (Ivacaftor label, Drug interactions)

Strong CYP3A4 or CYP2C9 Inhibitors Patients with renal or hepatic impairment who are taking strong inhibitors of CYP3A4 and CYP2C9 may have a significant increase in exposure to VIMPAT. (Lacosamide label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of lansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . (Lansoprazole label, Drug interactions)

Increased Risk of Bleeding : Concomitant use of NSAIDs, aspirin, other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk ( 5.5 ). (Levomilnacipran label, Warnings and precautions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

• Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

Drug Interactions Effects of Other Drugs on Loperamide Concomitant use of loperamide hydrochloride capsules with inhibitors of CYP3A4 (e.g., itraconazole) or CYP2C8 (e.g., gemfibrozil) or inhibitors of P-glycoprotein (e.g., quinidine, ritonavir) can increase exposure to loperamide. (Loperamide label, Drug interactions)

Strong CYP3A4 inhibitors: Recommended dosage is 10.5 mg once daily. (Lumateperone label, Drug interactions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. (Meloxicam label, Warnings and precautions)

• Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

Cytochrome P450-3A4 Inhibitors : May result in prolonged sedation due to decreased plasma clearance of midazolam. (Midazolam label, Drug interactions)

Examples phenytoin, carbamazepine, rifampin Strong CYP3A Inhibitors Clinical Impact The concomitant use of strong CYP3A inhibitors with REMERON/REMERONSolTab may increase the plasma concentration of mirtazapine [see Clinical Pharmacology (12.3) ] . (Mirtazapine label, Drug interactions)

Misoprostol does not exert clinically significant effects on the absorption, blood levels, and antiplatelet effects of therapeutic doses of aspirin. (Misoprostol label, Drug interactions)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. (Mometasone label, Warnings and precautions)

Consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of morphine or other opioid agonists. (Ticagrelor label, Drug interactions)

• Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

Moderate (e.g., fluconazole, atazanavir, aprepitant, diltiazem, erythromycin) and Strong (e.g., itraconazole, ketoconazole, clarithromycin, ritonavir, saquinavir) CYP3A Inhibitors Clinical Impact Increase in plasma naldemedine concentrations [see Clinical Pharmacology (12.3) ] Intervention Monitor for potential naldemedine-related adverse reactions [see Adverse… (Naldemedine label, Drug interactions)

Concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. (Naproxen label, Warnings and precautions)

CYP3A inhibitors such as fluconazole, itraconazole, clarithromycin, erythromycin, nefazodone, fluoxetine, saquinavir, indinavir, and nelfinavir may result in increased exposure to nifedipine when co-administered. (Nifedipine label, Drug interactions)

Coadministration of P-gp and CYP3A4 inhibitors may increase nintedanib exposure. (Nintedanib label, Drug interactions)

CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels. (Norethindrone and ethinyl estradiol label, Drug interactions)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (Norgestimate and ethinyl estradiol label, Drug interactions)

• Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of omeprazole [see Clinical Pharmacology ( 12.3 )] . (Omeprazole label, Drug interactions)

Co-administration with strong cytochrome P450 (CYP) 3A4 inhibitors (e.g., ketoconazole) increases the systemic exposure of oxybutynin. (Oxybutynin label, Drug interactions)

• Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk [see Drug Interactions ( 7.3 )] . (Paroxetine label, Warnings and precautions)

• Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

DRUG INTERACTIONS Bleeding has been reported in patients treated with pentoxifylline extended-release tablets with or without concomitant NSAIDs, anticoagulants, or platelet aggregation inhibitors. (Pentoxifylline label, Drug interactions)

Strong CYP3A4 Inhibitors: Reduce NUPLAZID dose to 10 mg once daily. (Pimavanserin label, Drug interactions)

• Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse effects. (Ticagrelor label, Drug interactions)

• Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse effects. (Ticagrelor label, Drug interactions)

CYP 3A4 inhibitors (e.g., ketoconazole, macrolide antibiotics): Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60% leading to an increased risk of corticosteroid side effects. (Prednisolone label, Drug interactions)

CYP 3A4 Inhibitors (e.g., Ketoconazole, Macrolide Antibiotics) Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60% leading to increased risk of corticosteroid side effects. (Prednisone label, Drug interactions)

• Concomitant use of strong CYP3A4 inhibitors: Reduce quetiapine dose to one‑sixth when coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) ( 2.5 , 7.1 , 12.3 ) (Quetiapine label, Drug interactions)

Ketoconazole (strong CYP3A4 inhibitor): Increases AUC for ramelteon; administer with caution. (Ramelteon label, Drug interactions)

CYP2C8 and CYP3A4 Inhibitors Intervention: Repaglinide tablets dose reductions and increased frequency of glucose monitoring may be required when co‑administered. (Repaglinide label, Drug interactions)

• Concomitant P-glycoprotein (P-gp) inhibitors (e.g., cyclosporine): Caution should be exercised when concomitant use of XIFAXAN and a P-glycoprotein inhibitor is needed. (Rifaximin label, Warnings and precautions)

Use with inhibitors of CYP3A4 or dual inhibitors of CYP3A4 and CYP1A2 (e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine) will increase roflumilast systemic exposure and may result in increased adverse reactions. (Roflumilast label, Drug interactions)

• Rosuvastatin plasma concentrations may increase. (Ticagrelor label, Drug interactions)

Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk ( 5.3 ) (Sertraline label, Warnings and precautions)

CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin) increase SILDENAFIL ORAL FILM exposure. (Sildenafil label, Drug interactions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. (Sumatriptan and naproxen label, Warnings and precautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (Tacrolimus label, Warnings and precautions)

…Physicians should be aware that CIALIS for once daily use provides continuous plasma tadalafil levels and should consider this when evaluating the potential for interactions with medications (e.g., nitrates, alpha-blockers, anti-hypertensives and potent inhibitors of CYP3A4) and with substantial consumption of alcohol [see Drug Interactions ( 7.1 , 7.2 , 7.3 )] . (Tadalafil label, Warnings and precautions)

• Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

Simultaneous administration of drugs that inhibit the activity of liver microsomal enzymes, i.e., CYP3A4 inhibitors such as cimetidine and ketoconazole, may prolong the half-life and decrease the plasma clearance of tinidazole, increasing the plasma concentrations of tinidazole. (Tinidazole label, Drug interactions)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (Tofacitinib label, Drug interactions)

Drug Interactions CYP3A4 Inhibitors Ketoconazole, an inhibitor of the drug metabolizing enzyme CYP3A4, significantly increased plasma concentrations of tolterodine when coadministered to subjects who were poor metabolizers (see CLINICAL PHARMACOLOGY, Variability in Metabolism and Drug-Drug Interactions ). (Tolterodine label, Drug interactions)

Co-administration of other strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin, cobicistat-containing products) with KENALOG-40 Injection may cause increased plasma concentration of triamcinolone leading to adverse reactions. (Triamcinolone label, Drug interactions)

Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the coadministration of Umeclidinium and Vilanterol ELLIPTA with ketoconazole and other known strong cytochrome P450 3A4 (CYP3A4) inhibitors (including, but not limited to, ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone,… (Umeclidinium and vilanterol label, Warnings and precautions)

In patients taking a strong CYP2D6 or CYP3A4 inhibitor, or who are CYP2D6 poor metabolizers, INGREZZA and INGREZZA SPRINKLE concentrations may be higher and QT prolongation clinically significant [see Clinical Pharmacology ( 12.2 )] . (Valbenazine label, Warnings and precautions)

Potential for Drug Interactions with Strong or Moderate CYP3A4 Inhibitors Concomitant administration with strong CYP3A4 inhibitors (such as ritonavir, indinavir, cobicistat, ketoconazole) or moderate CYP3A4 inhibitors (such as erythromycin) increases plasma concentrations of vardenafil. (Vardenafil label, Warnings and precautions)

Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and ODV. (Venlafaxine label, Drug interactions)

Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk ( 5.3 ) (Vilazodone label, Warnings and precautions)

CYP3A4 Substrates Clinical Impact Viloxazine is a weak inhibitor of CYP3A4 which increases the exposure of CYP3A4 substrates when coadministered [see Clinical Pharmacology (12.3) ]. (Viloxazine label, Drug interactions)

Vitamin E can inhibit platelet aggregation and vitamin K-dependent clotting, increasing bleeding risk with anticoagulant and antiplatelet drugs. (NIH Office of Dietary Supplements, Vitamin E)

• Increased Risk of Bleeding : Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, other antiplatelet drugs, warfarin, or other drugs that affect coagulation may increase risk ( 5.3 ). (Vortioxetine label, Warnings and precautions)

Closely monitor INR if a concomitant drug is a CYP2C9, 1A2, and/or 3A4 inhibitor or inducer. (Warfarin label, Drug interactions)

As zafirlukast is known to be an inhibitor of CYP3A4 in vitro , it is reasonable to employ appropriate clinical monitoring when these drugs are coadministered with zafirlukast. (Zafirlukast label, Precautions)

Drugs That Inhibit CYP3A4 CYP3A4 is a minor metabolic pathway for the elimination of zaleplon because the sum of desethylzaleplon (formed via CYP3A4 in vitro) and its metabolites, 5-oxo-desethylzaleplon and 5-oxo-desethylzaleplon glucuronide, account for only 9% of the urinary recovery of a zaleplon dose. (Zaleplon label, Drug interactions)

Ketoconazole Ketoconazole, a potent inhibitor of CYP3A4, at a dose of 400 mg QD for 5 days, increased the AUC and Cmax of ziprasidone by about 35-40%. (Ziprasidone label, Drug interactions)

CYP3A4 Inhibitors Ketoconazole Ketoconazole, a potent CYP3A4 inhibitor, increased the exposure to and pharmacodynamic effects of zolpidem. (Zolpidem label, Drug interactions)

Dapagliflozin or dapagliflozin 3-O-glucuronide did not meaningfully inhibit P-gp, OCT2, OAT1, or OAT3 active transporters. (Dapagliflozin label, Drug interactions)

The effect of potent CYP3A4 inhibitors on dutasteride has not been studied. (Dutasteride label, Drug interactions)

If possible, assess the presence of drug-dependent antiplatelet antibodies. (Ethosuximide label, Warnings)

An in vitro study using human liver microsomes suggests that famciclovir is not an inhibitor of CYP3A4 enzymes. (Famciclovir label, Drug interactions)

Omega-3 supplements may mildly prolong bleeding time; the combination with anticoagulants such as warfarin warrants monitoring, though clinically significant bleeding has not been consistently shown. (NIH Office of Dietary Supplements, Omega-3 Fatty Acids)

Additionally, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than fluoxetine or norfluoxetine as an inhibitor of the metabolism of several substrates for this enzyme, including astemizole, cisapride, and midazolam. (Fluoxetine label, Drug interactions)

Garlic supplements may increase bleeding risk with anticoagulants such as warfarin. (NCCIH, Garlic)

Effects of Noxafil and Noxafil PowderMix on Other Drugs Posaconazole is a strong CYP3A4 inhibitor. (Posaconazole label, Drug interactions)

Effects of Other Drugs on Ranolazine Strong CYP3A Inhibitors Concomitant use of ASPRUZYO Sprinkle with strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir is contraindicated [see Contraindications (4), Clinical Pharmacology (12.3)]. (Ranolazine label, Drug interactions)