Efavirenz, lamivudine, and tenofovir interactions

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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

• CYP3A Inhibitors: Avoid co-administration with strong CYP3A inhibitors. (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)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Hepatitis B antiviral agents Adefovir dipivoxil Concomitant administration of adefovir dipivoxil is not recommended. (Efavirenz, lamivudine, and tenofovir label, Drug 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)

Concomitant use of almotriptan tablets and potent CYP3A4 inhibitors should be avoided in patients with renal or hepatic impairment [see Clinical Pharmacology ( 12.3 )] . (Almotriptan label, Drug interactions)

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

• 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)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Atovaquone/ proguanil ↓ atovaquone ↓ proguanil Concomitant administration is not recommended. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Atovaquone/ proguanil ↓ atovaquone ↓ proguanil Concomitant administration is not recommended. (Efavirenz, lamivudine, and tenofovir 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)

Moderate CYP3A4/5 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, and nafcillin) may also reduce the plasma exposure of axitinib and should be avoided if possible. (Axitinib label, Drug interactions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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

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)

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

Concomitant use of strong CYP3A4 inhibitors (e.g., azole antimycotics, HIV protease inhibitors) with CYCLOSET should be avoided. (Bromocriptine label, Drug interactions)

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)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid taking a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) while taking COMETRIQ or reduce the dosage of COMETRIQ if concomitant use with strong CYP3A4 inhibitors cannot be avoided [see Dosage and Administration ( 2.2 ), Clinical Pharmacology… (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)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid use of Citalopram Capsules in CYP2C19 poor metabolizers, patients receiving concomitant cimetidine or another CYP2C19 inhibitor, patients with hepatic impairment, and patients who are greater than 60 years of age, because Citalopram Capsules are only available in a 30 mg dose strength and dosage adjustments are not possible [see Drug Interactions ( 7 ),… (Citalopram label, Warnings and precautions)

Antiviral and antiretroviral drugs: Avoid concomitant use. (Cladribine label, Drug interactions)

CYP2C19 inhibitors: Avoid concomitant use of omeprazole or esomeprazole. (Clopidogrel label, Warnings and precautions)

• 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)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid concomitant use of strong CYP3A4 inhibitors. (Dasatinib label, Drug interactions)

Avoid use of moderate or strong CYP3A4 inducers with EMFLAZA, as they may reduce efficacy ( 7.1 ) (Deflazacort label, Drug interactions)

• Avoid concomitant use of strong CYP3A4 inhibitors or inducers. (Dexamethasone label, Drug interactions)

QT Prolongation: Monitor ECG if concomitant use of drugs that prolong QT interval cannot be avoided or if concomitant CYP3A4 inhibitors used. (Dextromethorphan and quinidine label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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)

Concomitant use of Docetaxel Injection and drugs that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided. (Docetaxel label, Drug interactions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

• 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)

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)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir 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)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART) [see Warnings and Precautions (5.2) ] . (Entecavir 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)

WARNING Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of ergotamine tartrate and caffeine tablets with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. (Ergotamine and caffeine label, Boxed warning)

Avoid co-administering erlotinib with strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit or grapefruit juice) or a combined CYP3A4 and CYP1A2 inhibitor (e.g., ciprofloxacin). (Erlotinib label, Drug interactions)

Consequently, estazolam should be avoided in patients receiving ketoconazole and itraconazole, which are very potent inhibitors of CYP3A (see CONTRAINDICATIONS ). (Estazolam label, Warnings)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

• 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)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Cytochrome P450 3A4 Interaction The concomitant use of HYSINGLA ER 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 label, Boxed warning)

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)

Cytochrome P450 3A4 Interaction The concomitant use of Hydrocodone Polistirex and Chlorpheniramine Polistirex with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. (Hydrocodone and chlorpheniramine label, Boxed warning)

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

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Increased Toxicity with Concomitant Use of Antiretroviral Drugs Pancreatitis Pancreatitis (including fatal cases) have occurred in patients with HIV infection during therapy with hydroxyurea and didanosine, with or without stavudine. (Hydroxyurea label, Drug interactions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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

Antivirals Efavirenz Nevirapine Not recommended 2 weeks before and during TOLSURA treatment. (Itraconazole 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)

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

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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

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

Velpatasvir/Sofosbuvir ↓ velpatasvir Coadministration of EFV and sofosbuvir/velpatasvir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Concomitant administration of JUXTAPID with moderate or strong CYP3A4 inhibitors, as this can increase JUXTAPID exposure [see Warnings and Precautions (5.6) , Drug Interactions (7.1) , and Clinical Pharmacology (12.3) ]. (Lomitapide label, Contraindications)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

• Strong CYP3A Inhibitors : Avoid concomitant use; reduce LORBRENA dose if concomitant use cannot be avoided. (Lorlatinib 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)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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)

Although there have been no reports of such interactions with methylergonovine alone, strong and moderate CYP 3A4 inhibitors should not be co-administered with methylergonovine. (Methylergonovine label, Drug interactions)

CYP3A inducers: Do not use mifepristone with CYP3A inducers ( 7.3 ). (Mifepristone label, Drug interactions)

Strong CYP3A Inhibitors and Inducers: Avoid concomitant use. (Mitapivat label, Drug interactions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir 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)

Patients concomitantly using strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) because these medications can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning [see Drug Interactions (7.1) and Clinical Pharmacology… (Naloxegol label, Contraindications)

CYP2B6 Inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) may reduce efficacy by reducing bupropion exposure, avoid concomitant use. (Naltrexone and bupropion label, Drug interactions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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)

Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors [see Drug Interactions ( 7.1 , 7.2 )] . (Nilotinib label, Boxed warning)

Therefore, the concomitant administration of NYMALIZE and strong CYP3A4 inhibitors should generally be avoided [ see Warnings and Precautions (5.3) ]. (Nimodipine 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)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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 CYP3A4 Inhibitors : Avoid coadministration of VOTRIENT with strong CYP3A4 inhibitors. (Pazopanib label, Drug interactions)

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

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Posaconazole ↓ posaconazole Avoid concomitant use unless the benefit outweighs the risks. (Efavirenz, lamivudine, and tenofovir 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)

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)

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

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir 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)

Bictegravir 75 mg once a day 300 mg once a day (fasted) Healthy subjects ND ↓ AUC 38% ↓ C min 56% ↓ C max 20% Co-administration of rifabutin with Biktarvy (bictegravir/emtricitabine/ tenofovir alafenamide) is not recommended due to an expected decrease in tenofovir alafenamide in addition to the reported reduction in bictegravir. (Rifabutin label, Drug interactions)

…Concentrations Administered with rifampin 600 mg daily, unless otherwise specified AUC = area under the time-concentration curve Drug or Drug Class and Prevention or Management Clinical Effect Antiretrovirals Prevention or Management: Concomitant use is contraindicated (see CONTRAINDICATIONS ) Atazanavir Decrease AUC by 72% Darunavir Rifampin dosage used concomitantly with… (Rifampin label, Drug interactions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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

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

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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)

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)

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

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Severe renal impairment (CCr < 30 mL/min) Severe hepatic impairment (Child-Pugh score ≥ 10) Concomitant administration with strong Cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, ritonavir) [see DRUG INTERACTIONS (7.1) ] Patients with a history of hypersensitivity to silodosin or any of the ingredients in silodosin capsules… (Silodosin label, Contraindications)

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)

Velpatasvir/Sofosbuvir ↓ velpatasvir Coadministration of EFV and sofosbuvir/velpatasvir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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)

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

St. John's wort can lower blood levels of some HIV medicines enough to cause treatment failure. (NCCIH, St. John's Wort)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Concomitant use of JOURNAVX with strong CYP3A inhibitors is contraindicated [see Warnings and Precautions (5.1) , Drug Interactions (7.1) ] . (Suzetrigine label, Contraindications)

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)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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 SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

…dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS [see Warnings and Precautions (5.2) ] Unable to sense or respond to thirst Hypovolemic hyponatremia Taking strong CYP3A inhibitors [see Warnings and Precautions (5.5) ] Anuria Hypersensitivity (e.g., anaphylactic shock, rash generalized) to tolvaptan or any components of the product [see Adverse… (Tolvaptan label, Contraindications)

Drugs known to prolong the QT interval and strong CYP3A4 inhibitors should be avoided [see Warnings and Precautions (5.1) ] . (Toremifene label, Boxed warning)

CYP3A inhibitors: Avoid concomitant strong CYP3A inhibitors ( 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)

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)

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)

Avoid concomitant use of VEPPANU with strong CYP3A inhibitors or drugs known to prolong the QTc interval. (Vepdegestrant label, Warnings and precautions)

Therefore, the concomitant use of strong CYP3A inhibitors with vincristine sulfate should be avoided. (Vincristine label, Drug interactions)

…and herbal products that induce CYP2C19, CYP2C9, and/or CYP3A4 and for which significantly reduced voriconazole plasma concentrations may be associated with loss of efficacy [see Drug Interactions (7) ]: • Carbamazepine • Efavirenz Concomitant use with efavirenz dosages of 400 mg every 24 hours or higher is contraindicated [see Clinical Pharmacology (12.3) ] . (Voriconazole label, Contraindications)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Concomitant Drug Class: Drug Name Effect Clinical Comment Anticoagulant: Warfarin ↑ or ↓ warfarin Monitor INR and adjust warfarin dosage if necessary. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

HMG-CoA reductase inhibitors: Atorvastatin Pravastatin Simvastatin ↓ atorvastatin ↓ pravastatin ↓ simvastatin Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Use of Cytochrome P450 3A4 Inhibitors Ritonavir and other strong cytochrome P450 3A4 (CYP3A4) inhibitors can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see Drug Interactions ( 7.2 ) and Clinical Pharmacology ( 12.3 )] . (Azelastine and fluticasone label, Warnings and precautions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir 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)

Concomitant Drug Class: Drug Name Effect Clinical Comment Anticoagulant: Warfarin ↑ or ↓ warfarin Monitor INR and adjust warfarin dosage if necessary. (Efavirenz, lamivudine, and tenofovir 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)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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)

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Bupropion dose should not exceed the maximum recommended dose. (Efavirenz, lamivudine, and tenofovir 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)

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir 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)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, with carisoprodol could result in increased exposure of carisoprodol and decreased exposure of meprobamate. (Carisoprodol label, Drug interactions)

Amiodarone Amiodarone and its metabolite desethyl amiodarone, inhibitors of CYP2C9, and P- glycoprotein increased concentrations of the S(-)-enantiomer of carvedilol by at least 2 fold [see Clinical Pharmacology (12.5) ]. (Carvedilol label, Drug interactions)

Other Inducers of Hepatic CYP Enzymes Adults : When Caspofungin acetate for Injection is co-administered to adult patients with other inducers of hepatic CYP enzymes, such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, administration of a daily dose of 70 mg of Caspofungin acetate for Injection should be considered [see Dosage and Administration… (Caspofungin label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

In a drug interaction study, co-administration of orally inhaled ciclesonide and oral ketoconazole, a potent inhibitor of cytochrome P450 3A4, increased the exposure (AUC) of des-ciclesonide by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged. (Ciclesonide label, Drug interactions)

Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Strong and moderate CYP3A4 and CYP2C19 inhibitors: Increase exposure to cilostazol. (Cilostazol label, Drug interactions)

Co-administration with a strong CYP3A4 inhibitor may increase serum levels of cinacalcet. (Cinacalcet label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir 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)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Antifungals: Itraconazole Ketoconazole ↓ itraconazole ↓ hydroxyitraconazole ↓ ketoconazole Consider alternative antifungal treatment because no dose recommendation for itraconazole or ketoconazole can be made. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Concomitant administration of itraconazole, a strong CYP3A4 inhibitor, with DUAVEE, resulted in increases in bazedoxifene exposure (40%) and, to a lesser extent, conjugated estrogens exposure (9% for baseline-adjusted total estrone, 5% for total equilin), compared to DUAVEE alone [see Pharmacokinetics (12.3) ] . (Conjugated estrogens and bazedoxifene label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Concomitant Drug Class: Drug Name Effect Clinical Comment Anticoagulant: Warfarin ↑ or ↓ warfarin Monitor INR and adjust warfarin dosage if necessary. (Efavirenz, lamivudine, and tenofovir 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)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with dexlansoprazole may reduce antiviral effect and promote the development of drug resistance . (Dexlansoprazole label, Drug interactions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir 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)

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)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir 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)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Antifungals: Itraconazole Ketoconazole ↓ itraconazole ↓ hydroxyitraconazole ↓ ketoconazole Consider alternative antifungal treatment because no dose recommendation for itraconazole or ketoconazole can be made. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Concomitant Drug Class: Drug Name Effect Clinical Comment Anticoagulant: Warfarin ↑ or ↓ warfarin Monitor INR and adjust warfarin dosage if necessary. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Concomitant Drug Class: Drug Name Effect Clinical Comment Anticoagulant: Warfarin ↑ or ↓ warfarin Monitor INR and adjust warfarin dosage if necessary. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with esomeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ] . (Esomeprazole label, Drug interactions)

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)

Women who take medications that are strong CYP3A4 inducers should not choose Natazia as their oral contraceptive while using these inducers and for at least 28 days after discontinuation of these inducers due to the possibility of increased breakthrough bleeding and/or decreased contraceptive efficacy. (Estradiol and dienogest label, Drug interactions)

Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. (Estradiol and norethindrone 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)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Decreased exposure of etonogestrel may be expected. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Anti-infective: Clarithromycin ↓ clarithromycin ↑ 14-OH metabolite Consider alternatives to macrolide antibiotics because of the risk of QT interval prolongation. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

HMG-CoA reductase inhibitors: Atorvastatin Pravastatin Simvastatin ↓ atorvastatin ↓ pravastatin ↓ simvastatin Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Concomitant Drug Class: Drug Name Effect Clinical Comment Anticoagulant: Warfarin ↑ or ↓ warfarin Monitor INR and adjust warfarin dosage if necessary. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

…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)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Concomitant Drug Class: Drug Name Effect Clinical Comment Anticoagulant: Warfarin ↑ or ↓ warfarin Monitor INR and adjust warfarin dosage if necessary. (Efavirenz, lamivudine, and tenofovir 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)

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir 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)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with lansoprazole may reduce antiviral effect and promote the development of drug resistance. (Lansoprazole label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir 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)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Antimalarials: Artemether/lumefantrine ↓ artemether ↓ dihydroartemisinin ↓ lumefantrine Consider alternatives to artemether/lumefantrine because of the risk of QT interval prolongation [see Warnings and Precautions (5.16) ] . (Efavirenz, lamivudine, and tenofovir 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)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Hepatic Enzyme Inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin) : Drugs which induce cytochrome P450 3A4 enzyme activity may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased. (Methylprednisolone label, Drug interactions)

Antifungals: Itraconazole Ketoconazole ↓ itraconazole ↓ hydroxyitraconazole ↓ ketoconazole Consider alternative antifungal treatment because no dose recommendation for itraconazole or ketoconazole can be made. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

…salicylates, monoamine oxidase inhibitors, non-selective beta-adrenergic-blocking agents, anabolic hormones (e.g., methandrostenolone), guanethidine, gymnema sylvestre, glucomannan, thioctic acid, and inhibitors of CYP2C9 (e.g., amiodarone, fluconazole, voriconazole, sulfinpyrazone) or in patients known to be poor metabolizers of CYP2C9 substrates, alcohol. (Nateglinide label, Drug interactions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

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

Some drugs or herbal products that may decrease the effectiveness of HCs include efavirenz, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, rifabutin, rufinamide, aprepitant, and products containing St. (Norethindrone 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)

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

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Concomitant administration of CYP3A4 inhibitors may inhibit the metabolism of, and increase the mometasone furoate plasma concentration and potentially increase the risk for adverse reactions. (Olopatadine and mometasone label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir and nelfinavir) when used concomitantly with omeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology ( 12.3 )]. (Omeprazole label, Drug interactions)

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir and nelfinavir) when used concomitantly with omeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology ( 12.3 )] . (Omeprazole and sodium bicarbonate label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Drug Interactions and Decreased Vitamin Absorption ORLISTAT may interact with concomitant drugs including cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs, and antiretroviral drugs [see Drug Interactions (7) ]. (Orlistat label, Warnings and precautions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance. (Pantoprazole label, Drug interactions)

Exposure of Paricalcitol Injection will increase upon coadministration with strong CYP3A inhibitors [see Clinical Pharmacology (12.3) ] . (Paricalcitol label, Drug interactions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Drugs that induce CYP3A activity (e.g., phenobarbital, rifampin, rifabutin) would be expected to increase the clearance of EFV resulting in lowered plasma concentrations. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

HMG-CoA reductase inhibitors: Atorvastatin Pravastatin Simvastatin ↓ atorvastatin ↓ pravastatin ↓ simvastatin Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

HMG-CoA reductase inhibitors: Atorvastatin Pravastatin Simvastatin ↓ atorvastatin ↓ pravastatin ↓ simvastatin Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased. (Efavirenz, lamivudine, and tenofovir 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)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Antimalarials: Artemether/lumefantrine ↓ artemether ↓ dihydroartemisinin ↓ lumefantrine Consider alternatives to artemether/lumefantrine because of the risk of QT interval prolongation [see Warnings and Precautions (5.16) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Impact of Other Drugs on Propranolol CYP2D6, CYP1A2 and CYP2C19 Inhibitors: CYP2D6 inhibitors (e.g. bupropion, fluoxetine, paroxetine, quinidine), CYP1A2 inhibitors (e.g., ciprofloxacin, enoxamine, fluvoxamine) and CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine, ticlopidine) increase exposure to propranolol when co-administered with INNOPRAN XL. (Propranolol label, Drug interactions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Antimalarials: Artemether/lumefantrine ↓ artemether ↓ dihydroartemisinin ↓ lumefantrine Consider alternatives to artemether/lumefantrine because of the risk of QT interval prolongation [see Warnings and Precautions (5.16) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with rabeprazole may reduce antiviral effect and promote the development of drug resistance. (Rabeprazole label, Drug interactions)

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

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir 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)

Fixed-Dose Combination of Efavirenz, Emtricitabine, and Tenofovir Once-weekly coadministration of 900 mg PRIFTIN with the antiretroviral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg in HIV-infected patients did not result in any substantial change in steady state exposures of efavirenz, emtricitabine,… (Rifapentine label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Coadministration of a selective and potent inhibitor of CYP3A4, ketoconazole (100 mg bid for 2 days with ropivacaine infusion administered 1 hour after ketoconazole) caused a 15% reduction in in vivo plasma clearance of ropivacaine. (Ropivacaine label, Drug interactions)

HMG-CoA reductase inhibitors: Atorvastatin Pravastatin Simvastatin ↓ atorvastatin ↓ pravastatin ↓ simvastatin Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Strong CYP3A4 Inhibitors: Reduce, interrupt, or discontinue JAKAFI/JAKAFI XR doses as recommended except in patients with acute or chronic graft-versus-host-disease. (Ruxolitinib label, Drug interactions)

Strong Inhibitors of CYP3A4/5 Enzymes Ketoconazole significantly increased saxagliptin exposure. (Saxagliptin label, Drug interactions)

Strong Inhibitors of CYP3A4/5 Enzymes Ketoconazole significantly increased saxagliptin exposure. (Saxagliptin and metformin label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

Sertraline ↓ sertraline Increases in sertraline dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

The possibility of interactions with other drugs administered concurrently should be considered, particularly when their main route of elimination is active renal secretion via the organic cationic transport system (e.g., trimethoprim) [see Clinical Pharmacology (12.3) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Monitor QT interval more frequently when SUTENT is concomitantly administered with strong CYP3A4 inhibitors or drugs known to prolong QT interval. (Sunitinib label, Warnings and precautions)

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

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

…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)

Antimalarials: Artemether/lumefantrine ↓ artemether ↓ dihydroartemisinin ↓ lumefantrine Consider alternatives to artemether/lumefantrine because of the risk of QT interval prolongation [see Warnings and Precautions (5.16) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Narcotic analgesic: Methadone ↓ methadone Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

CYP3A4 Substrates (e.g., midazolam) and CYP2B6 Substrates (e.g., bupropion, efavirenz): Efficacy of concomitant drugs may be decreased; monitor patients’ response and consider increasing the dosage of the concomitant drug, if necessary. (Telotristat 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)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir 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)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

CYP3A4 inducers/inhibitors: Monitor for decreased tinidazole effect or increased adverse reactions ( 7.2 ) (Tinidazole label, Drug interactions)

Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

CYP2C9: Concomitant use with CYP2C9 inhibitors can decrease torsemide clearance. (Torsemide label, Drug interactions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir 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)

The possibility of interactions with other drugs administered concurrently should be considered, particularly when their main route of elimination is active renal secretion via the organic cationic transport system (e.g., trimethoprim) [see Clinical Pharmacology (12.3) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir 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)

Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] . (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir 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)

Inhibitors of CYP3A4: May cause earlier onset and/or increased severity of adverse reactions ( 7.1 ) (Vinorelbine label, Drug interactions)

Antidepressants: Bupropion ↓ bupropion Increases in bupropion dosage should be guided by clinical response. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Concomitant Drug Class: Drug Name Effect Clinical Comment Anticoagulant: Warfarin ↑ or ↓ warfarin Monitor INR and adjust warfarin dosage if necessary. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Zafirlukast exposure is likely to be increased by other moderate and strong CYP2C9 inhibitors. (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)

QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving TDF. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving TDF. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Hormonal contraceptives: Oral Ethinyl estradiol/ Norgestimate ↓ active metabolites of norgestimate A reliable method of barrier contraception should be used in addition to hormonal contraceptives. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

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

Hormonal contraceptives: Oral Ethinyl estradiol/ Norgestimate ↓ active metabolites of norgestimate A reliable method of barrier contraception should be used in addition to hormonal contraceptives. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Hormonal contraceptives: Oral Ethinyl estradiol/ Norgestimate ↓ active metabolites of norgestimate A reliable method of barrier contraception should be used in addition to hormonal contraceptives. (Efavirenz, lamivudine, 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)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Hormonal contraceptives: Oral Ethinyl estradiol/ Norgestimate ↓ active metabolites of norgestimate A reliable method of barrier contraception should be used in addition to hormonal contraceptives. (Efavirenz, lamivudine, and tenofovir 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)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Hormonal contraceptives: Oral Ethinyl estradiol/ Norgestimate ↓ active metabolites of norgestimate A reliable method of barrier contraception should be used in addition to hormonal contraceptives. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Hormonal contraceptives: Oral Ethinyl estradiol/ Norgestimate ↓ active metabolites of norgestimate A reliable method of barrier contraception should be used in addition to hormonal contraceptives. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Hormonal contraceptives: Oral Ethinyl estradiol/ Norgestimate ↓ active metabolites of norgestimate A reliable method of barrier contraception should be used in addition to hormonal contraceptives. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

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)

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

Hormonal contraceptives: Oral Ethinyl estradiol/ Norgestimate ↓ active metabolites of norgestimate A reliable method of barrier contraception should be used in addition to hormonal contraceptives. (Efavirenz, lamivudine, and tenofovir 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)

Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving TDF. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

However, no formal drug-drug interaction studies between zileuton and CYP3A4 inhibitors, such as ketaconazole, have been conducted. (Zileuton label, Drug interactions)

Drugs without Clinically Significant Interactions No dosage adjustment is recommended when SYMFI is administered with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, and lorazepam. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Drugs without Clinically Significant Interactions No dosage adjustment is recommended when SYMFI is administered with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, and lorazepam. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Drugs without Clinically Significant Interactions No dosage adjustment is recommended when SYMFI is administered with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, and lorazepam. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Drugs without Clinically Significant Interactions No dosage adjustment is recommended when SYMFI is administered with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, and lorazepam. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)

Effect of Other Drugs on Micafungin in Sodium Chloride Injection CYP3A4, CYP2C9 and CYP2C19 Inhibitors Co-administration of Micafungin in Sodium Chloride Injection with cyclosporine, itraconazole, voriconazole and fluconazole 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)

Drugs without Clinically Significant Interactions No dosage adjustment is recommended when SYMFI is administered with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, and lorazepam. (Efavirenz, lamivudine, and tenofovir label, Drug interactions)