Mitotane interactions

CYP3A4 Inducers: Avoid concomitant strong CYP3A4 inducers during YONSA treatment. (Abiraterone label, Drug interactions)

• CYP3A Inducers: Avoid co-administration with strong CYP3A inducers. (Acalabrutinib 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. (Acetaminophen and codeine label, Boxed warning)

CYP3A4 Inducers : Avoid coadministration of VIJOICE with a strong CYP3A4 inducer. (Alpelisib label, Drug interactions)

• 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)

• when coadministered with drugs that are strong inducers of CYP3A due to the potential for loss of therapeutic effect and development of resistance. (Atazanavir label, Contraindications)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

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)

Strong CYP3A4 Inducers: Avoid concomitant use. (Bortezomib label, Drug interactions)

• Strong CYP3A Inducers: Avoid concomitant use with BOSULIF. (Bosutinib label, Drug interactions)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

Evaluate patients starting CYP3A4 inhibitors or stopping CYP3A4 inducers at frequent intervals for respiratory depression. (Buprenorphine 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. (Butalbital, acetaminophen, caffeine, and codeine label, Boxed warning)

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (Butalbital, aspirin, caffeine, and codeine label, Boxed warning)

Avoid chronic co-administration of strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. (Cabozantinib 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)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

• 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)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Moderate or Strong CYP3A4 inducers: Avoid concomitant use. (Daridorexant label, Drug interactions)

Co-administration of PREZCOBIX or PREZCOBIX PED with CYP3A inducers may lead to lower exposures of darunavir and cobicistat and potential loss of efficacy of darunavir and possible resistance. (Darunavir and cobicistat label, Contraindications)

If concomitant administration of a strong CYP3A4 inducer cannot be avoided, consider a dose increase [see Dosage and Administration ( 2.3 )] . (Dasatinib label, Drug interactions)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

These drugs include, but are not limited to, the following: the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin the androgen receptor inhibitor enzalutamide the antimycobacterials rifampin, rifapentine the cytotoxic agent mitotane St. (Doravirine label, Contraindications)

• Avoid concomitant use of doxorubicin hydrochloride with inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp ( 7.1 ) (Doxorubicin label, Drug interactions)

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

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

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)

Strongly induce CYP3A, which may lead to lower exposure of one or more components and loss of efficacy of GENVOYA and possible resistance. (Elvitegravir, cobicistat, emtricitabine, and tenofovir label, Contraindications)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane 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)

Preventing or Managing DI The concomitant use of ADDYI with CYP3A4 inducers is not recommended. (Flibanserin label, Drug interactions)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentration. (Hydrocodone label, Boxed warning)

In addition, discontinuation of a concomitantly used Cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentrations. (Hydrocodone and acetaminophen label, Boxed warning)

In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentration. (Hydrocodone and chlorpheniramine label, Boxed warning)

In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentration. (Hydrocodone and homatropine label, Boxed warning)

In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentration. (Hydrocodone and ibuprofen label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

• Strong CYP3A4 Inducers: Do not administer strong CYP3A4 inducers with CAMPTOSAR. (Irinotecan label, Drug interactions)

Avoid concomitant use of CYP3A4 inducers when using Corlanor. (Ivabradine label, Drug interactions)

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

Avoid strong CYP3A4 inducers. (Lapatinib label, Drug interactions)

Strong CYP3A4 Inducers: Avoid coadministration of strong CYP3A4 inducers with VITRAKVI. (Larotrectinib label, Drug interactions)

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

Concomitant administration of SUNLENCA with strong CYP3A inducers is contraindicated due to decreased lenacapavir plasma concentrations, which may result in the loss of therapeutic effect and development of resistance to SUNLENCA [see Drug Interactions (7.1) ] . (Lenacapavir label, Contraindications)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Effect of Other Drugs on LORBRENA Strong CYP3A Inducers LORBRENA is contraindicated in patients taking strong CYP3A inducers [see Contraindication (4) ] . (Lorlatinib label, Drug interactions)

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

Strong CYP3A4 inducers (e.g., rifampin, avasimibe, St. (Lurasidone label, Contraindications)

Strong CYP3A4 inducers (rifampin) reduce exposure to macitentan: avoid co-administration with OPSUMIT ( 7.1 , 12.3 ). (Macitentan label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in meperidine plasma concentration. (Meperidine label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

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)

Strong CYP3A4 inducers (e.g., rifampin) : Decreased concentrations of naloxegol; concomitant use is not recommended. (Naloxegol label, Drug interactions)

John’s Wort reduce the bioavailability and efficacy of nifedipine; therefore nifedipine should not be used in combination with strong CYP3A inducers such as rifampin (See CONTRAINDICATIONS ). (Nifedipine label, Drug interactions)

Strong CYP3A Inducers: Avoid concomitant use with CAVHANZA. (Nilotinib 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)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

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

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. (Oxycodone label, Boxed warning)

In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. (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)

VOTRIENT is not recommended if chronic use of strong CYP3A4 inducers cannot be avoided. (Pazopanib label, Drug interactions)

Strong or Moderate CYP3A4 Inducers: Avoid concomitant use of NUPLAZID. (Pimavanserin label, Drug interactions)

• Patients taking strong Cytochrome P450 3A enzyme (CYP3A) inducers, such as rifampin, [see Warnings and Precautions ( 5.6 ) and Drug Interactions ( 7.1 , 7.2 )] . (Praziquantel label, Contraindications)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

Hormonal contraceptives: Avoid concomitant use with LYSODREN. (Mitotane 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, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine. (Promethazine and codeine label, Boxed warning)

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 and Moderate CYP3A Inducers: Avoid concomitant administration. (Rimegepant label, Drug interactions)

• Certain CYP3A inducers: Coadministration with strong inducers of CYP3A is not recommended. (Ritlecitinib label, Drug interactions)

Avoid concomitant use of XARELTO with drugs that are known combined P-gp and strong CYP3A inducers [see Drug Interactions (7.3) ] . (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)

Intervention: Avoid the use of VARUBI in patients who require chronic administration of strong CYP3A4 inducers. (Rolapitant label, Drug interactions)

• Avoid use with rifampin and strong CYP3A4 inducers ( 7.3 ). (Romidepsin 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)

• Strong CYP3A Inducers: Avoid strong CYP3A4 inducers. (Sorafenib label, Drug interactions)

Spironolactone: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

Spironolactone: Avoid concomitant use with LYSODREN. (Mitotane label, Drug interactions)

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

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 co-administration of strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (e.g., rifampin, phenytoin) with TEPADINA due to the potential effects on efficacy and toxicity [see Clinical Pharmacology ( 12.3 ) ] . (Thiotepa label, Drug interactions)

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

Avoid concomitant use of SAMSCA with strong CYP3A inducers. (Tolvaptan label, Drug interactions)

Coadministration with a strong CYP3A4 inducer may result in a relevant decrease in FARESTON exposure and should be avoided. (Toremifene label, Drug interactions)

CYP3A inducers: Avoid concomitant strong CYP3A inducers ( 7.1 ) (Trabectedin 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)

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 tramadol are complex. (Tramadol and acetaminophen label, Boxed warning)

Avoid concomitant use with strong CYP3A inducers if possible. (Tretinoin label, Drug interactions)

If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. (Mitotane label, Boxed warning)

Strong CYP3A4 Inducers: Should be avoided as concomitant use will result in reduction of ubrogepant exposure. (Ubrogepant label, Drug interactions)

Ella should not be administered with CYP3A4 inducers [see Drug interactions (7.1) and Clinical Pharmacology (12.3) ] . (Ulipristal label, Warnings and precautions)

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)

Strong CYP3A Inducers : Avoid concomitant use with strong CYP3A inducers. (Vepdegestrant label, Drug interactions)

Warfarin: Avoid concomitant use with LYSODREN. (Mitotane 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)

Prolonged Bleeding Time LYSODREN can cause platelet function disorders due to abnormal adenosine diphosphate (ADP)-induced platelet aggregation. (Mitotane label, Warnings and precautions)

• Use with CYP3A Inducers: Increase the risk of reduced efficacy of alprazolam. (Alprazolam label, Drug interactions)

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (Amlodipine label, Drug interactions)

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (Amlodipine and atorvastatin label, Drug interactions)

Blood pressure should be monitored when amlodipine is coadministered with CYP3A4 inducers (e.g. rifampicin, St. (Amlodipine and benazepril label, Drug interactions)

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (Amlodipine and olmesartan label, Drug interactions)

Blood pressure should be closely monitored when amlodipine is coadministered with CYP3A inducers (e.g. rifampicin, St. (Amlodipine and valsartan label, Drug interactions)

CYP3A4/5 Inducers Co-administration of rifampin, a strong inducer of CYP3A4/5, reduced the plasma exposure of axitinib in healthy volunteers. (Axitinib label, Drug interactions)

Clinically Significant Interactions with Bexagliflozin Tablets UGT Enzyme Inducers Clinical Impact UGT Enzyme Inducers may significantly reduce exposure to bexagliflozin and lead to a decreased efficacy [ see Clinical Pharmacology ( 12.3 )]. (Bexagliflozin label, Drug interactions)

Strong CYP3A4 inducers Double the recommended dosage and further adjust based on clinical response. (Brexpiprazole label, Drug interactions)

Therefore, potent inhibitors or inducers of CYP3A4 may increase or reduce the circulating levels of CYCLOSET, respectively. (Bromocriptine label, Drug interactions)

Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inducers can decrease the plasma concentration of buprenorphine [see Clinical Pharmacology (12.3) ] , potentially resulting in decreased efficacy… (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)

Inducers of Hepatic CYP Enzymes Rifampin : Rifampin is a potent CYP3A4 inducer and concomitant administration with caspofungin acetate for injection is expected to reduce the plasma concentrations of caspofungin acetate for injection. (Caspofungin label, Drug interactions)

Miscellaneous Cytochrome P450 Inducers: Efavirenz Nevirapine Rifampicin Rifabutin Rifapentine Use With Caution Inducers of CYP3A enzymes, such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine will increase the metabolism of clarithromycin, thus decreasing plasma concentrations of clarithromycin, while increasing those of 14-OH-clarithromycin. (Clarithromycin label, Drug interactions)

Inducers of CYP3A4 and CYP3A5 Inducers of CYP3A4 and/or CYP3A5 may reduce plasma concentrations of clindamycin. (Clindamycin label, Drug interactions)

…several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. (Clomipramine label, Drug interactions)

Due to increased steroid clearance and increase of steroid-binding protein, high-dose replacement therapy may be required and free cortisol and corticotropin (ACTH) should be monitored to adapt the systemic corticosteroids. (Mitotane label, Warnings and precautions)

Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of PREZISTA/ritonavir, respectively. (Darunavir label, Warnings and precautions)

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)

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)

Examples Glutethimide and phenobarbital Intervention If a patient initiates or discontinues therapy with an enzyme inducer, dose adjustment of doxercalciferol may be necessary. (Doxercalciferol label, Drug interactions)

Coadministration of RPV and drugs that induce CYP3A may result in decreased plasma concentrations of RPV and loss of virologic response and possible resistance to RPV or to the class of NNRTIs. (Emtricitabine, rilpivirine, and tenofovir label, Drug interactions)

CYP3A4 Inducers Pre-treatment with a CYP3A4 inducer prior to erlotinib decreased erlotinib exposure [see Clinical Pharmacology (12.3) ]. (Erlotinib label, Drug interactions)

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)

While no in vivo drug-drug interaction studies were conducted between estazolam and inducers of CYP3A, compounds that are potent CYP3A inducers (such as carbamazepine, phenytoin, rifampin, and barbiturates) would be expected to decrease estazolam concentrations. (Estazolam label, Warnings)

Drugs that Induce CYP3A4 (Rifampicin) Racemic zopiclone exposure was decreased 80% by concomitant use of rifampicin, a potent inducer of CYP3A4. (Eszopiclone label, Drug interactions)

Strong CYP3A inducer and P-gp inducer : Increase the dosage as recommended. (Everolimus label, Drug interactions)

Strong CYP 3A4 inducers: Concomitant use of strong CYP 3A4 inducers decreases exemestane exposure. (Exemestane label, Drug interactions)

Phenobarbital Clinical Impact: Chronic administration of phenobarbital, a known enzyme inducer, may be associated with a decrease in the plasma half-life of fenoprofen. (Fenoprofen label, Drug interactions)

CYP3A4 Inducers No dosing adjustments are recommended in the presence of CYP3A4 inducers, such as rifampin and carbamazepine. (Fesoterodine 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)

Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of fosamprenavir calcium/ritonavir, respectively. (Fosamprenavir label, Warnings and precautions)

CYP3A4 Interactions: Fosaprepitant is a weak inhibitor of CYP3A4, and aprepitant, the active moiety, is a substrate, inhibitor, and inducer of CYP3A4; see Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustment of FOCINVEZ and concomitant drugs. (Fosaprepitant label, Warnings and precautions)

• CYP3A4 Inducer: Increase IRESSA to 500 mg daily in patients receiving a strong CYP3A4 inducer. (Gefitinib label, Drug interactions)

…and its plasma concentrations can be significantly affected resulting in an increase in exposure Consider dose reduction [see Dosage and administration (2.7) ] Strong and moderate CYP3A4 inducers, e.g., rifampin, efavirenz Guanfacine is primarily metabolized by CYP3A4 and its plasma concentrations can be significantly affected resulting in a decrease in exposure… (Guanfacine label, Drug interactions)

Drugs that May Decrease Haloperidol Plasma Concentrations Coadministration of haloperidol with potent enzyme inducers of CYP3A4 may gradually decrease the plasma concentrations of haloperidol to such an extent that efficacy may be reduced. (Haloperidol label, Drug interactions)

• CYP3A4 Inducers: Monitor for increased toxicity when used in combination with CYP3A4 inducers. (Ifosfamide label, Drug interactions)

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

The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary. (Imipramine 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)

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)

…Drugs That May Alter T 4 and Triiodothyronine (T 3 ) Serum Transport Without Effecting Free Thyroxine (FT 4 ) Concentration (Euthyroidism) Drug or Drug Class Effect Clofibrate Estrogen-containing oral contraceptives Estrogens (oral) Heroin/Methadone 5-Fluorouracil Mitotane Tamoxifen These drugs may increase serum thyroxine-binding globulin (TBG) concentration. (Levothyroxine label, Drug interactions)

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

Inducers of P-glycoprotein or CYP3A4 Enzymes Clinical Impact Rifampin decreased linagliptin exposure, suggesting that the efficacy of linagliptin may be reduced when administered in combination with a strong P-gp or CYP3A4 inducer. (Linagliptin and metformin label, Drug interactions)

Table 2: Drugs That May Alter Triiodothyronine (T3) Serum Transport Without Affecting Free Thyroxine (FT4) Concentration (Euthyroidism) Drug or Drug Class Effect Clofibrate Estrogen-containing oral contraceptives Estrogens (oral) Heroin/Methadone 5-Fluorouracil Mitotane Tamoxifen These drugs may increase serum thyroxine-binding globulin (TBG) concentration. (Liothyronine label, Drug interactions)

…Nasal/Ophthalmic Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone prednisone triamcinolone ↓ lopinavir ↑ glucocorticoids Coadministration with oral dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to lopinavir. (Lopinavir and ritonavir label, Drug interactions)

• If patients with severe renal impairment or ESRD receiving SELZENTRY (without concomitant CYP3A inducers or inhibitors) experience postural hypotension, the dose of SELZENTRY should be reduced from 300 mg twice daily to 150 mg twice daily. (Maraviroc label, Warnings and precautions)

Rifampin (Potent Inducer of CYP3A4) Coadministration of a single 500 mg oral dose of mefloquine and 600 mg of rifampin once daily for 7 days in 7 healthy Thai volunteers resulted in a decrease in the mean C max and AUC of mefloquine by 19% and 68%, respectively, and a decrease in the mean elimination half-life of mefloquine from 305 hours to 113 hours. (Mefloquine label, Drug interactions)

Inducers of CYP3A4 (e.g., phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital) could increase the rate of elimination of donepezil. (Memantine and donepezil label, Drug interactions)

…agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration… (Methadone label, Drug interactions)

CYP3A4 inducers Drugs (e.g. nevirapine, rifampin) that are strong inducers of CYP3A4 are likely to decrease the pharmacological action of methylergonovine maleate. (Methylergonovine 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)

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

Possible Reduced Efficacy with Strong CYP3A4 Inducers Concomitant use of strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. (Nimodipine label, Warnings and precautions)

Coadministration with oral doses of a P-gp and CYP3A4 inducer, rifampicin, decreased exposure to nintedanib by 50%. (Nintedanib label, Drug interactions)

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (Olmesartan, amlodipine, and hydrochlorothiazide label, Drug interactions)

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)

Table 6: 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 and sodium bicarbonate 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)

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)

• Concomitant use of strong CYP3A4 inducers: Increase quetiapine dose up to 5 fold when used in combination with a chronic treatment (more than 7-14 days) of potent CYP3A4 inducers (e.g., phenytoin, rifampin, St. (Quetiapine label, Drug interactions)

Antiepileptics (AEDs) (Carbamazepine, Phenobarbital, and Phenytoin) Carbamazepine, phenobarbital, and phenytoin are CYP3A4 inducers and may decrease quinine plasma concentrations if used concurrently with quinine sulfate. (Quinine label, Drug interactions)

Rifampin (strong CYP enzyme inducer): Decreases exposure to and effects of ramelteon. (Ramelteon label, Drug interactions)

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

Drug Interactions Effect of Rifabutin on the Pharmacokinetics of Other Drugs Rifabutin induces CYP3A enzymes and therefore may reduce the plasma concentrations of drugs metabolized by those enzymes. (Rifabutin label, Drug interactions)

Coadministration of EDURANT or EDURANT PED and drugs that induce CYP3A may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs. (Rilpivirine label, Drug interactions)

Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. (Risperidone 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)

Strong CYP3A4 Inducers Concomitant use of JAKAFI/JAKAFI XR with strong CYP3A4 inducers may decrease ruxolitinib exposure [ see Clinical Pharmacology ( 12.3 )] , which may reduce efficacy of JAKAFI/JAKAFI XR. (Ruxolitinib 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 Inducers : Consider dose increase of SUTENT when administered with strong CYP3A4 inducers. (Sunitinib label, Drug interactions)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Suvorexant label, Drug interactions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (Tacrolimus label, Warnings and precautions)

CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) increase CIALIS exposure ( 2.7 , 5.10 , 7.2 ) requiring dose adjustment: CIALIS for use as needed: no more than 10 mg every 72 hours CIALIS for once daily use: dose not to exceed 2.5 mg CYP3A4 inducers (e.g. rifampin) decrease CIALIS exposure ( 7.2 ). (Tadalafil label, Drug interactions)

Patients should be monitored for adequate clinical effect when amlodipine is co-administered with CYP3A4 inducers. (Telmisartan and amlodipine label, Drug interactions)

Co-administration with Inducers or Inhibitors of CYP3A Metabolism Agents Inducing CYP3A Metabolism: Strong inducers of CYP3A4/5 such as dexamethasone, carbamazepine, phenytoin, phenobarbital, rifampin, rifabutin, and rifampacin may decrease exposure of the active metabolite, sirolimus. (Temsirolimus label, Warnings and precautions)

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

DRUG INTERACTIONS Hepatic microsomal enzyme inducing agents, such as carbamazepine, were found to significantly increase the clearance of thiothixene. (Thiothixene 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)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (Tofacitinib label, Drug interactions)

CYP3A4 Inducers: Increase in RALDESY dosage may be necessary ( 2.5 , 7 ). (Trazodone label, Drug interactions)

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

Strong Inducers of CYP 3A Clinical implication Coadministration of triazolam with strong inducers of CYP3A4 can significantly decrease the plasma concentration of triazolam and may decrease effectiveness of triazolam. (Triazolam 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. (Valproic acid label, Drug interactions)

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

CYP3A4 Inducers: Consider increasing VIIBRYD dosage by 2-fold, up to 80 mg once-daily over 1 to 2 weeks when used concomitantly with strong CYP3A4 inducers for greater than 14 days ( 2.4 , 7 ). (Vilazodone label, Drug interactions)

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)

The selective serotonin reuptake inhibitors sertraline (weak CYP3A4 inducer) and fluoxetine (CYP2D6 inhibitor), and the anti-epileptic drug felbamate (CYP2C19 inhibitor and CYP3A4 inducer) do not affect the pharmacokinetics of clonazepam. (Clonazepam label, Drug interactions)

Drug Interactions If phenytoin or other hepatic enzyme inducers are taken concurrently with Norpace or Norpace CR, lower plasma levels of disopyramide may occur. (Disopyramide label, Drug interactions)

• Cytochrome P450 3A4 inducers, inhibitors, or substrates: May alter docetaxel metabolism. (Docetaxel label, Drug interactions)

TAF is not an inhibitor or inducer of CYP3A in vivo . (Emtricitabine and tenofovir label, Drug interactions)

Effects of Other Drugs on HALAVEN No drug-drug interactions are expected with CYP3A4 inhibitors, CYP3A4 inducers or P-glycoprotein (P-gp) inhibitors. (Eribulin label, Drug interactions)

Potential for Etravirine to Affect Other Drugs Etravirine is an inducer of CYP3A and inhibitor of CYP2C9, CYP2C19 and P-glycoprotein (P-gp). (Etravirine label, Drug interactions)

Potential for Glycerol Phenylbutyrate to Affect Other Drugs Drugs with narrow therapeutic index that are substrates of CYP3A4 Glycerol phenylbutyrate is a weak inducer of CYP3A4 in humans. (Glycerol phenylbutyrate label, Drug interactions)

In cases of cognitive dysfunction, thyroid function should be evaluated as mitotane may induce hypothyroidism. (Mitotane label, Warnings and precautions)

In cases of cognitive dysfunction, thyroid function should be evaluated as mitotane may induce hypothyroidism. (Mitotane label, Warnings and precautions)

When phenytoin or other hepatic enzyme inducers such as rifampin and phenobarbital have been taken concurrently with mexiletine, lowered mexiletine plasma levels have been reported. (Mexiletine label, Drug interactions)

In cases of cognitive dysfunction, thyroid function should be evaluated as mitotane may induce hypothyroidism. (Mitotane label, Warnings and precautions)

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)

In cases of cognitive dysfunction, thyroid function should be evaluated as mitotane may induce hypothyroidism. (Mitotane label, Warnings and precautions)

Concurrent use of strong CYP3A inducers (e.g., St. (Vincristine 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)

CYP2C19 and CYP3A4 Inducer Co-administration of Micafungin in Sodium Chloride Injection with rifampin and ritonavir did not alter the pharmacokinetics of micafungin. (Micafungin 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)