Aprepitant 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)

• Simultaneous use of combined P-gp and strong CYP3A4 inducers reduces blood levels of apixaban: Avoid concomitant use. (Apixaban label, Drug interactions)

Drug Interactions : Use with strong cytochrome P450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended because loss of efficacy may occur ( 5.5 , 7.1 ) (Apremilast label, Warnings and precautions)

CYP3A4 Inducers : Avoid concomitant use for greater than 14 days ( 7.1 ) (Aripiprazole label, Drug interactions)

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 is contraindicated with: dofetilide due to the potential for increased dofetilide plasma concentrations and associated serious and/or life-threatening events. strong CYP3A inducers due to decreased plasma concentrations of BIC and LEN, which may result in the loss of therapeutic effect and development of resistance to BIXLENVO. (Bictegravir, emtricitabine, and tenofovir alafenamide label, Contraindications)

Co-administration of such combinations of a CYP2C9 inhibitor plus a strong or moderate CYP3A inhibitor with TRACLEER is not recommended. (Bosentan label, Drug interactions)

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

Intervention: Concomitant use of VRAYLAR with a CYP3A4 inducer is not recommended [see Dosage and Administration ( 2.1 , 2.6 ) ] . (Cariprazine label, Drug interactions)

• Concomitant use of Strong CYP3A4 Inducers is not recommended. (Clozapine label, Drug interactions)

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)

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

• Avoid concomitant use of strong CYP3A4 inhibitors or inducers. (Dexamethasone 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)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

• CYP3A inducers: Avoid concomitant use. (Dronedarone label, Drug interactions)

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)

• 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)

Therefore, concomitant use with strong CYP3A inducers is not recommended [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . (Elexacaftor, tezacaftor, and ivacaftor label, Warnings and precautions)

…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)

VYTORIN is contraindicated in the following conditions: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see Drug Interactions (7.1) ] . (Ezetimibe and simvastatin label, Contraindications)

• 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)

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)

…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)

Therefore, administration of potent enzyme inducers of CYP3A4 with ketoconazole tablets is not recommended. (Ketoconazole label, Drug interactions)

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

Concomitant administration with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and cobicistat-containing products) (see WARNINGS , Myopathy/Rhabdomyolysis ). (Lovastatin label, Contraindications)

CYP3A4 inducers: Avoid concomitant use with CAPLYTA. (Lumateperone label, Drug interactions)

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

Strong CYP3A4 inducers (rifampin) reduce exposure to macitentan: avoid co-administration with OPSUMIT ( 7.1 , 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)

Similarly, discontinuation of concomitant CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers in METHADOSE-treated patients may increase methadone plasma concentrations resulting in fatal respiratory depression. (Methadone label, Warnings and precautions)

John's Wort) Clinical Impact Significant decrease in plasma naldemedine concentrations, which may reduce efficacy [see Clinical Pharmacology (12.3) ] Intervention Avoid use of SYMPROIC with strong CYP3A inducers. (Naldemedine label, Drug interactions)

Avoid co-administration of nifedipine with phenytoin or any known CYP3A4 inducer or consider an alternative antihypertensive therapy. (Nifedipine label, Drug interactions)

…contraindicated with drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. (Nirmatrelvir and ritonavir label, Contraindications)

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)

Counsel patients to use a back-up method or alternative method of contraception when enzyme inducers are used with COCs ( 7.1 ) -- - ---------- ------ USE IN SPECIFIC POPULATIONS---- -- -- --------- ---- Lactation: Not recommended; Lo Loestrin Fe can decrease milk production ( 8.2 ) (Norethindrone and ethinyl estradiol label, Drug interactions)

If a CYP3A4 inducer is discontinued, consider OLINVYK dosage reduction and monitor for signs of respiratory depression. (Oliceridine 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)

• CYP3A Inducers: Avoid concurrent use of IBRANCE with strong CYP3A inducers. (Palbociclib label, Drug interactions)

Strong CYP3A4 and P-glycoprotein (P-gp) inducers : Avoid using a strong inducer of CYP3A4 and/or P-gp during a dosing interval for ERZOFRI. (Paliperidone label, Drug interactions)

Strong or Moderate CYP3A4 Inducers: Avoid concomitant use of NUPLAZID. (Pimavanserin 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)

ASPRUZYO Sprinkle is contraindicated in patients: Taking strong inhibitors of CYP3A [see Drug Interactions (7.1)] Taking inducers of CYP3A [see Drug Interactions (7.1)] With liver cirrhosis [see Use in Specific Populations (8.6)] Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nelfinavir) (4, 7.1) (Ranolazine label, Contraindications)

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

Use with P-gp and Strong CYP3A Inhibitors or Inducers Avoid concomitant use of XARELTO with known combined P-gp and strong CYP3A inhibitors [see Drug Interactions (7.2) ] . (Rivaroxaban label, Warnings and precautions)

• Drug Interactions: Use with strong cytochrome P450 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin) is not recommended. (Roflumilast label, Warnings and precautions)

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

ZOCOR is contraindicated in the following conditions: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see Drug Interactions (7.1) ] . (Simvastatin label, Contraindications)

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)

Inducers of CYP3A4 Strong CYP3A4 inducers should not be used with tamoxifen. (Tamoxifen label, Drug interactions)

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

Strong CYP3A4 inducers (e.g., rifampin): Avoid use of HETLIOZ in combination with rifampin or other CYP3A4 inducers, because of decreased exposure ( 7.2 , 12.3 ) (Tasimelteon label, Drug interactions)

• 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)

Strong CYP3A4 Inducers : Coadministration of RINVOQ/RINVOQ LQ with strong CYP3A4 inducers is not recommended. (Upadacitinib label, Drug interactions)

Use of strong CYP3A4 inducers with INGREZZA or INGREZZA SPRINKLE Concomitant use is not recommended. (Valbenazine label, Drug interactions)

John's wort, a CYP3A4 inducer, in combination with zolpidem may decrease blood levels of zolpidem and is not recommended. (Zolpidem 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)

LIPITOR plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and transporters. (Atorvastatin 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)

Inhibitors of CYP3A4 Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inhibitors can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of buprenorphine and naloxone sublingual tablet is achieved. (Buprenorphine and naloxone 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)

Table 7: Clinically Significant Drug Interactions with INVOKANA UGT Enzyme Inducers Clinical Impact: UGT enzyme inducers decrease canagliflozin exposure which may reduce the effectiveness of INVOKANA. (Canagliflozin label, Drug interactions)

• Strong inducer of CYP3A4 or CYP2C19: Consider dose increase of EPIDIOLEX. (Cannabidiol (prescription) label, Drug interactions)

It may be necessary to reduce the EQUETRO dose if used concomitantly with inhibitors of CYP3A4 and/or epoxide hydrolase. (Carbamazepine label, Drug interactions)

Co-administration of celecoxib with drugs that are known to inhibit CYP2C9 (e.g., fluconazole) may enhance the exposure and toxicity of celecoxib whereas co-administration with CYP2C9 inducers (e.g., rifampin) may lead to compromised efficacy of celecoxib. (Celecoxib label, Drug interactions)

Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ] . (Aprepitant label, Drug interactions)

Inhibitors of CYP3A4 or CYP2C19 Inhibitors of CYP3A4 Coadministration of strong (e.g., ketoconazole) and moderate (e.g., erythromycin, diltiazem and grapefruit juice) CYP3A4 inhibitors can increase exposure to cilostazol. (Cilostazol label, Drug interactions)

Examples Moderate inhibitor : diltiazem Strong inhibitors : ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of CINVANTI [see Clinical Pharmacology (12.3)… (Aprepitant label, Drug interactions)

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)

Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ] . (Aprepitant label, Drug interactions)

Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ] . (Aprepitant label, Drug interactions)

Hormonal Contraceptives : Efficacy of contraceptives may be reduced during and for 28 days following administration of aprepitant. (Aprepitant label, Warnings and precautions)

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

Closely monitor patients for signs of reduced effectiveness when deferasirox is administered with drugs metabolized by CYP3A4 (e.g., alfentanil, aprepitant, budesonide, buspirone, conivaptan, cyclosporine, darifenacin, darunavir, dasatinib, dihydroergotamine, dronedarone, eletriptan, eplerenone, ergotamine, everolimus, felodipine, fentanyl, hormonal contraceptive… (Deferasirox label, Drug interactions)

Clinically Relevant Interactions Affecting DEXILANT When Coadministered with Other Drugs and Substances CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of dexlansoprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ] . (Dexlansoprazole label, Drug interactions)

Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ] . (Aprepitant label, Drug interactions)

Co-administration of diclofenac with CYP2C9 inhibitors (e.g., voriconazole) may enhance the exposure and toxicity of diclofenac whereas co-administration with CYP2C9 inducers (e.g. rifampin) may lead to compromised efficacy of diclofenac. (Diclofenac label, Drug interactions)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Divalproex (valproate) label, Drug interactions)

Concomitant medications were 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… (Dofetilide label, Drug interactions)

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

Inhibitors and Inducers of CYP2C9 and CYP3A4 : May alter dronabinol systemic exposure; monitor for dronabinol-related adverse reactions or loss of efficacy. (Dronabinol label, Drug interactions)

Hormonal Contraceptives : Efficacy of contraceptives may be reduced during and for 28 days following administration of aprepitant. (Aprepitant label, Warnings and precautions)

Table 4: Clinically Relevant Interactions Affecting Esomeprazole When Co-Administered with Other Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Esomeprazole label, Drug interactions)

Hormonal Contraceptives : Efficacy of contraceptives may be reduced during and for 28 days following administration of aprepitant. (Aprepitant label, Warnings and precautions)

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)

Interaction With Strong Inhibitors and Inducers of CYP3A4 Coadministration of Zortress with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, boceprevir, telaprevir) or strong CYP3A4 inducers (e.g., rifampin, rifabutin) is not recommended without close monitoring of everolimus whole blood trough… (Everolimus label, Warnings and precautions)

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)

Limited data in patients receiving known enzyme inducers ( phenytoin, phenobarbital, carbamazepine ) indicate only a 30% increase in the rate of flecainide elimination. (Flecainide 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)

…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)

CYP3A4 Inducers Clinical Impact CYP3A4 inducers decrease haloperidol exposure (haloperidol is a CYP3A4 substrate) [see Clinical Pharmacology (12.3) ]. (Haloperidol 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)

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

CYP3A4 inducers may decrease Gleevec C max and area under curve (AUC). (Imatinib label, Drug interactions)

Examples Moderate inhibitor : diltiazem Strong inhibitors : ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of CINVANTI [see Clinical Pharmacology (12.3)… (Aprepitant label, Drug interactions)

Concomitant Use with CYP3A Inducers Use of KALYDECO with strong CYP3A inducers, such as rifampin, substantially decreases the exposure of ivacaftor, which may reduce the therapeutic effectiveness of KALYDECO. (Ivacaftor label, Warnings and precautions)

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)

Clinically Relevant Interactions Affecting PREVACID or PREVACID SoluTab When Coadministered with Other Drugs CYP2C19 OR CYP3A4 Inducers Clinical Impact: Decreased exposure of lansoprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ] . (Lansoprazole label, Drug interactions)

Strong CYP3A4 inhibitors : Maximum recommended dosage is 80 mg once daily ( 7 ). (Levomilnacipran label, Drug interactions)

Hormonal Contraceptives : Efficacy of contraceptives may be reduced during and for 28 days following administration of aprepitant. (Aprepitant label, Warnings and precautions)

Hormonal Contraceptives : Efficacy of contraceptives may be reduced during and for 28 days following administration of aprepitant. (Aprepitant label, Warnings and precautions)

Strong P-glycoprotein/CYP3A4 inducer: The efficacy of TRADJENTA may be reduced when administered in combination (e.g., with rifampin). (Linagliptin 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)

Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ] . (Aprepitant label, Drug interactions)

Hormonal Contraceptives : Efficacy of contraceptives may be reduced during and for 28 days following administration of aprepitant. (Aprepitant label, Warnings and precautions)

Hormonal Contraceptives : Efficacy of contraceptives may be reduced during and for 28 days following administration of aprepitant. (Aprepitant label, Warnings and precautions)

Methylprednisolone Clinical Impact Increased methylprednisolone exposure [see Clinical Pharmacology (12.3) ] . (Aprepitant label, Drug interactions)

Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ] . (Aprepitant label, Drug interactions)

John's Wort, tramadol, tryptophan, buspirone Strong CYP3A Inducers Clinical Impact The concomitant use of strong CYP3A inducers with REMERON/REMERONSolTab decreases the plasma concentration of mirtazapine [see Clinical Pharmacology (12.3) ] . (Mirtazapine label, Drug interactions)

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

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

Hormonal Contraceptives : Efficacy of contraceptives may be reduced during and for 28 days following administration of aprepitant. (Aprepitant label, Warnings and precautions)

Hormonal Contraceptives : Efficacy of contraceptives may be reduced during and for 28 days following administration of aprepitant. (Aprepitant label, Warnings and precautions)

Table 4: Clinically Relevant Interactions Affecting Omeprazole When Co-Administered with Other Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of omeprazole when used concomitantly with strong inducers [see Clinical Pharmacology ( 12.3 )] . (Omeprazole label, Drug interactions)

Phenytoin, Carbamazepine, and Rifampin In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampin), the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased. (Ondansetron 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)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (Perampanel label, Drug interactions)

Strong CYP3A4 Inducers: Decreased exposure of WAKIX; consider dosage adjustment of WAKIX ( 2.6 , 7.1 ) (Pitolisant label, Drug interactions)

CYP 3A4 inducers (e.g. barbiturates, phenytoin, carbamazepine, and rifampin): Drugs such as barbiturates, phenytoin, ephedrine, and rifampin, which induce hepatic microsomal drug metabolizing enzyme activity may enhance metabolism of prednisolone and require that the dosage of Orapred be increased. (Prednisolone label, Drug interactions)

CYP 3A4 inducers and inhibitors: May, respectively, increase or decrease clearance of corticosteroids, necessitating dose adjustment. (Prednisone label, Drug interactions)

Hormonal Contraceptives : Efficacy of contraceptives may be reduced during and for 28 days following administration of aprepitant. (Aprepitant label, Warnings and precautions)

• 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)

Rifampin (strong CYP enzyme inducer): Decreases exposure to and effects of ramelteon. (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)

Use of CINVANTI with strong CYP3A4 inducers (e.g., rifampin) may result in a reduction in aprepitant plasma concentrations and decreased efficacy of CINVANTI. (Aprepitant label, Warnings and precautions)

Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. (Risperidone label, Drug interactions)

Examples Moderate inhibitor : diltiazem Strong inhibitors : ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of CINVANTI [see Clinical Pharmacology (12.3)… (Aprepitant label, Drug interactions)

Effects of Other AEDs on BANZEL Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of BANZEL (see Table 6). (Rufinamide label, Drug interactions)

Drugs that induce CYP3A4 (e.g., phenytoin, carbamazepine, nafcillin, phenobarbital, and rifampin) should be used with caution. (Selegiline label, Drug interactions)

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

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). (Suvorexant label, Drug interactions)

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)

Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ] . (Aprepitant label, Drug interactions)

Terbinafine clearance is increased 100% by rifampin, a CYP450 enzyme inducer, and decreased 33% by cimetidine, a CYP450 enzyme inhibitor. (Terbinafine label, Drug interactions)

Use of tiagabine HCl without enzyme-inducing antiepileptic drugs results in blood levels about twice those attained in the studies on which current dosing recommendations are based (see DOSAGE AND ADMINISTRATION ). (Tiagabine label, Warnings)

CYP3A4 inducers/inhibitors: Monitor for decreased tinidazole effect or increased adverse reactions ( 7.2 ) (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)

Concomitant use of CYP2C9 inducers (e.g., rifampin) increase torsemide clearance and decrease plasma torsemide concentrations. (Torsemide label, Drug interactions)

Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. (Treprostinil label, Warnings and precautions)

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)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Valproic acid label, Drug interactions)

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)

CYP3A4 inducers decrease verapamil levels ( 7.1 ) (Verapamil label, Drug interactions)

CYP3A4 Inhibitors: The VIIBRYD dose should not exceed 20 mg once daily when co-administered with strong CYP3A4 inhibitors ( 2.4 , 7 ). (Vilazodone label, Drug interactions)

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)

Warfarin (a CYP2C9 substrate) : Risk of decreased INR of prothrombin time; monitor INR in 2–week period, particularly at 7 to 10 days, following initiation of CINVANTI. (Aprepitant label, Warnings and precautions)

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)

Multiple-dose administration of the potent CYP3A4 inducer rifampin (600 mg every 24 hours, q24h, for 14 days), however, reduced zaleplon C max and AUC by approximately 80%. (Zaleplon label, Drug interactions)

Pharmacokinetic Interactions Carbamazepine Carbamazepine is an inducer of CYP3A4; administration of 200 mg twice daily for 21 days resulted in a decrease of approximately 35% in the AUC of ziprasidone. (Ziprasidone label, Drug interactions)

CYP3A4 Inducers If co-administration with a potent CYP3A4 inducer is necessary, the patient should be closely monitored and the dose of ZONISAMIDE and other drugs that CYP3A4 substrates may need to be adjusted [see Clinical Pharmacology ( 12.3 )] . (Zonisamide label, Drug interactions)

Drugs Metabolized by CYP3A Results of in vitro studies demonstrate that duloxetine does not inhibit or induce CYP3A activity. (Duloxetine label, Drug interactions)

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

TAF is a weak inhibitor of CYP3A in vitro . (Emtricitabine and tenofovir label, Drug interactions)

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

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)

Examples ondansetron, granisetron, dolasetron 7.2 Effect of Other Drugs on the Pharmacokinetics of Aprepitant Aprepitant is a CYP3A4 substrate [see Clinical Pharmacology (12.3) ] . (Aprepitant label, Drug interactions)

Examples rifampin, carbamazepine, phenytoin (Aprepitant label, Drug interactions)

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

CYP3A4 Substrates An in vitro study has suggested that rifaximin induces CYP3A4 [see Clinical Pharmacology ( 12.3 )] . (Rifaximin label, Drug interactions)

Strong CYP3A inducers: Strong inducers of CYP3A (for example, rifampin, phenytoin, carbamazepine, phenobarbital or St. (Riociguat label, Drug interactions)

Drugs Having No Clinically Important Interactions with SAPHRIS No dosage adjustment of SAPHRIS is necessary when administered concomitantly with paroxetine (see Table 12 in Drug Interactions ( 7.1 ) for paroxetine dosage adjustment), imipramine, cimetidine, valproate, lithium, or a CYP3A4 inducer (e.g., carbamazepine, phenytoin, rifampin). (Asenapine label, Drug interactions)

…adjustment is needed when SINGULAIR is co-administered with theophylline, prednisone, prednisolone, oral contraceptives, fexofenadine, digoxin, warfarin, gemfibrozil, itraconazole, thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, and Cytochrome P450 (CYP) enzyme inducers [see Clinical Pharmacology (12.3) ]. (Montelukast label, Drug interactions)

Other HIV Protease Inhibitors (CYP3A4 Inhibition) In Vivo Studies Showed No Significant Effects of Indinavir on Voriconazole Exposure In Vitro Studies Demonstrated Potential for Inhibition of Voriconazole Metabolism (Increased Plasma Exposure) No dosage adjustment in the voriconazole dosage needed for concomitant administration with indinavir. (Voriconazole label, Drug interactions)