Everolimus interactions

It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants [see Warnings and Precautions (5.2) ] . (Adalimumab label, Boxed warning)

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

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

If serotonin syndrome occurs, discontinue ADDERALL XR and the CYP2D6 inhibitor [see Warnings and Precautions ( 5.8 ), Overdosage ( 10 )] . (Amphetamine and dextroamphetamine label, Drug interactions)

For patients receiving ELIQUIS at a dose of 2.5 mg twice daily, avoid coadministration with combined P-gp and strong CYP3A4 inhibitors [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3) ] . (Apixaban label, Drug interactions)

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

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

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

About 13 percent of the cases of neutropenia have ended fatally, but almost all fatalities were in patients with serious illness, having collagen vascular disease, renal failure, heart failure or immunosuppressant therapy, or a combination of these complicating factors. (Captopril label, Warnings)

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

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)

Nephrotoxicity Increased nephrotoxicity can occur with use of standard doses of cyclosporine in combination with Zortress. (Everolimus label, Boxed warning)

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

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

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

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

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

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

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

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

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

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

Chicken pox and measles, for example, can have a more serious or even fatal course in children on immunosuppressant corticosteroids. (Fludrocortisone label, Warnings)

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)

Interaction With Grapefruit Juice Grapefruit and grapefruit juice inhibit cytochrome P450 3A4 and P-gp activity and should therefore be avoided with concomitant use of Zortress and cyclosporine or tacrolimus. (Everolimus label, Warnings and precautions)

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)

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

…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)

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

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

If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate and the CYP2D6 inhibitor [see Warnings and Precautions (5.7) and Overdosage (10) ] . (Lisdexamfetamine 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)

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

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

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

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

CYP2D6 Inhibitors Monitor patients closely when the combination use of CYP2D6 inhibitor and metoprolol cannot be avoided. (Metoprolol label, Drug interactions)

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

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)

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

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

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

Concurrent treatment with strong inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, boceprevir, telaprevir) and inducers (e.g., rifampin, rifabutin) of CYP3A4 is not recommended. (Everolimus label, Drug interactions)

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

Concurrent treatment with strong inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, boceprevir, telaprevir) and inducers (e.g., rifampin, rifabutin) of CYP3A4 is not recommended. (Everolimus label, Drug interactions)

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

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

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

Hypersensitivity to everolimus, sirolimus, or to components of the drug product ( 4 ) (Everolimus label, Contraindications)

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)

St. John's wort can weaken these medicines by speeding up their breakdown, which can mean organ rejection, clots, or loss of effect. (NCCIH, St. John's Wort)

Interaction With Grapefruit Juice Grapefruit and grapefruit juice inhibit cytochrome P450 3A4 and P-gp activity and should therefore be avoided with concomitant use of Zortress and cyclosporine or tacrolimus. (Everolimus label, Warnings and precautions)

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

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

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

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

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

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

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

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

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

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

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

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

Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) (Everolimus label, Warnings and precautions)

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

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

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

Strong CYP2D6 Inhibitors Prevention or Management With concomitant use of atomoxetine oral solution and a strong CYP2D6 inhibitor 1 , increase the titration interval [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] . (Atomoxetine label, Drug interactions)

Atorvastatin (CYP3A4 Substrate) and Pravastatin (P-gp Substrate) Single-dose administration of Zortress with either atorvastatin or pravastatin to healthy subjects did not influence the pharmacokinetics of atorvastatin, pravastatin and everolimus, as well as total HMG-CoA reductase bioreactivity in plasma to a clinically relevant extent. (Everolimus label, Drug interactions)

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

Other Possible Interactions Moderate inhibitors of CYP3A4 and P-gp may increase everolimus blood concentrations (e.g., fluconazole; macrolide antibiotics; nicardipine, diltiazem; nelfinavir, indinavir, amprenavir). (Everolimus label, Drug interactions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) (Everolimus label, Warnings and precautions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

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)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

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

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

Cannabidiol Drug Interactions When cannabidiol and Zortress are coadministered, closely monitor for an increase in everolimus blood levels and for adverse reactions suggestive of everolimus toxicity. (Everolimus label, Warnings and precautions)

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

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

CYP2D6 Inhibitors and Poor Metabolizers Interactions of carvedilol with potent inhibitors of CYP2D6 isoenzyme (such as quinidine, fluoxetine, paroxetine, and propafenone) have not been studied, but these drugs would be expected to increase blood levels of the R(+) enantiomer of carvedilol [see Clinical Pharmacology (12.3) ]. (Carvedilol label, Drug interactions)

Cannabidiol Drug Interactions When cannabidiol and Zortress are coadministered, closely monitor for an increase in everolimus blood levels and for adverse reactions suggestive of everolimus toxicity. (Everolimus label, Warnings and precautions)

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

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

Ketoconazole and Other Strong CYP3A4 Inhibitors Multiple-dose ketoconazole administration to healthy volunteers significantly increased single dose estimates of everolimus C max , AUC, and half-life. (Everolimus 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)

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

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

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

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

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

Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections. (Denosumab label, Warnings and precautions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

Concomitant use of strong CYP2D6 inhibitors: Maximum recommended dose of AUSTEDO XR or AUSTEDO is 36 mg per day ( 2.3 , 7.1 ) (Deutetrabenazine label, Drug interactions)

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

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

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

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

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

CYP2D6 inhibitors may potentiate systemic beta-blockade. (Dorzolamide and timolol label, Drug interactions)

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

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

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

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)

Similar effects would be expected with other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine) [see Warnings and Precautions ( 5.12 )] . (Duloxetine label, Drug interactions)

When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index such as cyclosporine, everolimus, sirolimus and tacrolimus, caution and appropriate monitoring should be used [see Clinical Pharmacology (12.3) ] . (Elexacaftor, tezacaftor, and ivacaftor label, Drug interactions)

Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) (Everolimus label, Warnings and precautions)

Erythromycin (Moderate CYP3A4 Inhibitor) Multiple-dose erythromycin administration to healthy volunteers significantly increased single dose estimates of everolimus C max , AUC, and half-life. (Everolimus label, Drug interactions)

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

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

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

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

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

During Zortress therapy with cyclosporine, patients administered an HMG-CoA reductase inhibitor and/or fibrate should be monitored for the possible development of rhabdomyolysis and other adverse effects, as described in the respective labeling for these agents [ see Drug Interactions (7 . (Everolimus label, Warnings and precautions)

Other Possible Interactions Moderate inhibitors of CYP3A4 and P-gp may increase everolimus blood concentrations (e.g., fluconazole; macrolide antibiotics; nicardipine, diltiazem; nelfinavir, indinavir, amprenavir). (Everolimus label, Drug interactions)

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

Ketoconazole and Other Strong CYP3A4 Inhibitors Multiple-dose ketoconazole administration to healthy volunteers significantly increased single dose estimates of everolimus C max , AUC, and half-life. (Everolimus label, Drug interactions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

During Zortress therapy with cyclosporine, patients administered an HMG-CoA reductase inhibitor and/or fibrate should be monitored for the possible development of rhabdomyolysis and other adverse effects, as described in the respective labeling for these agents [ see Drug Interactions (7 . (Everolimus label, Warnings and precautions)

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

Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) (Everolimus label, Warnings and precautions)

During Zortress therapy with cyclosporine, patients administered an HMG-CoA reductase inhibitor and/or fibrate should be monitored for the possible development of rhabdomyolysis and other adverse effects, as described in the respective labeling for these agents [ see Drug Interactions (7 . (Everolimus label, Warnings and precautions)

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

…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)

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

CYP3A4 and/or CYP2D6 Inhibitors Clinical Impact CYP3A4 and/or CYP2D6 inhibitors increase haloperidol exposure (haloperidol is a CYP3A4 and CYP2D6 substrate) [see Clinical Pharmacology (12.3) ]. (Haloperidol label, Drug interactions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

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

Ketoconazole and Other Strong CYP3A4 Inhibitors Multiple-dose ketoconazole administration to healthy volunteers significantly increased single dose estimates of everolimus C max , AUC, and half-life. (Everolimus label, Drug interactions)

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

Ketoconazole and Other Strong CYP3A4 Inhibitors Multiple-dose ketoconazole administration to healthy volunteers significantly increased single dose estimates of everolimus C max , AUC, and half-life. (Everolimus label, Drug interactions)

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

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

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

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

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

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

Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) (Everolimus label, Warnings and precautions)

Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) (Everolimus label, Warnings and precautions)

CYP2D6 Inhibitors : Concomitant use of paroxetine resulted in increased plasma levels of Lofexidine tablets. (Lofexidine label, Drug interactions)

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

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

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

• Strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) : See Full Prescribing Information for recommended dosage reductions. (Metoclopramide label, Drug interactions)

Midazolam (CYP3A4/5 Substrate) Single-dose administration of midazolam to healthy volunteers following administration of multiple-dose Zortress indicated that everolimus is a weak inhibitor of CYP3A4/5. (Everolimus label, Drug interactions)

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

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

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

Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) (Everolimus label, Warnings and precautions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

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

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

Use with CYP2D6 Inhibitors Nebivolol exposure increases with inhibition of CYP2D6 [see Drug Interactions ( 7 ) ] . (Nebivolol label, Warnings and precautions)

Other Possible Interactions Moderate inhibitors of CYP3A4 and P-gp may increase everolimus blood concentrations (e.g., fluconazole; macrolide antibiotics; nicardipine, diltiazem; nelfinavir, indinavir, amprenavir). (Everolimus label, Drug interactions)

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

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

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

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

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

Inhibitors of CYP2D6 Fluoxetine: Fluoxetine (60 mg single dose or 60 mg daily dose for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance. (Olanzapine label, Drug interactions)

Risk of Use in Patients with Decreased Cytochrome P450 2D6 Function or Concomitant Use or Discontinuation with Cytochrome P450 3A4 Inhibitors and Inducers Risk of Increased Oliceridine Plasma Concentrations Increased plasma concentrations of oliceridine, which may result in prolonged opioid adverse reactions and exacerbated respiratory depression, may occur when… (Oliceridine label, Warnings and precautions)

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

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

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

Ketoconazole and Other Strong CYP3A4 Inhibitors Multiple-dose ketoconazole administration to healthy volunteers significantly increased single dose estimates of everolimus C max , AUC, and half-life. (Everolimus label, Drug interactions)

Cimetidine Increased plasma concentration of paroxetine Use caution if BRISDELLE is used concomitantly with other drugs that inhibit CYP2D6 (e.g., quinidine). (Paroxetine label, Drug interactions)

Ketoconazole and Other Strong CYP3A4 Inhibitors Multiple-dose ketoconazole administration to healthy volunteers significantly increased single dose estimates of everolimus C max , AUC, and half-life. (Everolimus label, Drug interactions)

Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) (Everolimus label, Warnings and precautions)

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

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

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

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

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

During Zortress therapy with cyclosporine, patients administered an HMG-CoA reductase inhibitor and/or fibrate should be monitored for the possible development of rhabdomyolysis and other adverse effects, as described in the respective labeling for these agents [ see Drug Interactions (7 . (Everolimus label, Warnings and precautions)

Strong CYP2D6 Inhibitors: Increased exposure of WAKIX; reduce the maximum recommended dose of WAKIX by half ( 2.6 , 7.1 ) (Pitolisant label, Drug interactions)

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

Atorvastatin (CYP3A4 Substrate) and Pravastatin (P-gp Substrate) Single-dose administration of Zortress with either atorvastatin or pravastatin to healthy subjects did not influence the pharmacokinetics of atorvastatin, pravastatin and everolimus, as well as total HMG-CoA reductase bioreactivity in plasma to a clinically relevant extent. (Everolimus label, Drug interactions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

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

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)

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

Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) (Everolimus label, Warnings and precautions)

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

Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) (Everolimus label, Warnings and precautions)

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

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)

Fluoxetine and Paroxetine Fluoxetine (20 mg once daily) and paroxetine (20 mg once daily), CYP 2D6 inhibitors, have been shown to increase the plasma concentration of risperidone 2.5–2.8 fold and 3–9 fold respectively. (Risperidone label, Drug interactions)

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

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

During Zortress therapy with cyclosporine, patients administered an HMG-CoA reductase inhibitor and/or fibrate should be monitored for the possible development of rhabdomyolysis and other adverse effects, as described in the respective labeling for these agents [ see Drug Interactions (7 . (Everolimus label, Warnings and precautions)

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

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

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

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

…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)

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

• Do not exceed 50 mg/day and the maximum single dose should not exceed 25 mg if administered in conjunction with a strong CYP2D6 inhibitor (e.g., fluoxetine, paroxetine). (Tetrabenazine label, Warnings and precautions)

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

CYP2D6 Inhibitors Potentiated systemic beta-blockade (e.g., decreased heart rate) has been reported during combined treatment with CYP2D6 inhibitors (e.g., quinidine) and timolol. (Timolol label, Drug interactions)

Cyclosporine, tacrolimus: Monitor for toxicities of these immunosuppressive drugs ( 7.1 ) (Tinidazole label, Drug interactions)

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

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

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

Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) (Everolimus label, Warnings and precautions)

Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) (Everolimus label, Warnings and precautions)

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)

Lymphomas and Other Malignancies Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. (Everolimus label, Warnings and precautions)

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

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

Therefore, the potential exists for a drug interaction between drugs that inhibit CYP2D6-mediated metabolism of venlafaxine, reducing the metabolism of venlafaxine to ODV, resulting in increased plasma concentrations of venlafaxine and decreased concentrations of the active metabolite. (Venlafaxine label, Drug interactions)

Verapamil (CYP3A4 and P-gp Substrate) Multiple-dose verapamil administration to healthy volunteers significantly increased single dose estimates of everolimus C max and AUC. (Everolimus label, Drug interactions)

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

CYP2D6 Substrates Clinical Impact Viloxazine is a weak inhibitor of CYP2D6, and increases the exposure of CYP2D6 substrates when coadministered [see Clinical Pharmacology (12.3) ] . (Viloxazine label, Drug interactions)

• Strong inhibitors of CYP2D6: Reduce TRINTELLIX dose by half when coadministered ( 2.5 , 7.1 ). (Vortioxetine label, Drug interactions)

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

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

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

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

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

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

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

CYP2D6 substrates Clinical Impact: In vitro studies indicate that celecoxib, although not a substrate, is an inhibitor of CYP2D6. (Celecoxib label, Drug interactions)

Drugs which inhibit CYP2D6 and CYP3A3/4 also inhibit the metabolism of cevimeline. (Cevimeline label, Drug interactions)

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

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

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

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus 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)

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

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

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

• CYP2D6 inhibitors: As meclizine is metabolized by CYP2D6, there is a potential for drug-drug interactions between meclizine hydrochloride and CYP2D6 inhibitors ( 7.2 ). (Meclizine label, Drug interactions)

In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. (Methimazole label, Warnings)

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. (Propylthiouracil label, Warnings)

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

Drugs Metabolized by CYP2D6 Clinical Impact: Sertraline hydrochloride capsules are a CYP2D6 inhibitor [see Clinical Pharmacology ( 12.3 )] . (Sertraline label, Drug interactions)

Strong Inhibitors of CYP2D6 The impact on the efficacy of tamoxifen with co-administration of strong CYP2D6 inhibitors (e.g., paroxetine) is not well established. (Tamoxifen label, Drug interactions)

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)