Nelfinavir

Strong CYP3A4 inhibitor causing significant increases in colchicine plasma levels.

Anticipated significant increase in saxagliptin plasma concentrations. Do not coadminister with dapagliflozin and saxagliptin.

Strong CYP3A4 inhibitor; rare reports of serious adverse events including vasospasm leading to cerebral ischemia and ischemia of extremities.

Concomitant use is not recommended. Co-administration decreases nelfinavir serum levels (AUC decreased by 92%, Cmax by 89%, Cmin by 75%) and active metabolite M8 levels.

Concomitant use is not recommended. Esomeprazole magnesium decreases nelfinavir serum levels, potentially reducing therapeutic effectiveness.

Esomeprazole magnesium decreases nelfinavir serum levels (AUC decreased by 92%), which may result in loss of therapeutic effect and development of drug resistance.

Concomitant use not recommended. Esomeprazole substantially decreases nelfinavir serum levels (AUC decreased by 92%, Cmax by 89%), reducing therapeutic efficacy.

Strong CYP3A4 inhibitor; concomitant use is contraindicated due to increased risk of myopathy and rhabdomyolysis.

Strong CYP3A4 inhibitor; concomitant use is contraindicated due to increased risk of hypotension and syncope.

Strong CYP3A4 inhibitor may increase systemic corticosteroid effects of fluticasone propionate.

Strong CYP3A4 inhibitor may increase systemic corticosteroid and cardiovascular adverse effects when used with fluticasone propionate and salmeterol.

CYP3A4 inhibitor may increase systemic exposure to irinotecan or SN-38. Do not administer unless no therapeutic alternatives.

Strong CYP3A4 inhibitor that increases ivabradine plasma concentrations, exacerbating bradycardia and conduction disturbances.

Concomitant use of strong CYP3A4 inhibitors (such as boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, tipranavir/ritonavir, voriconazole) with lomitapide is contraindicated.

HIV protease inhibitor and strong CYP 3A4 inhibitor; should not be co-administered due to risk of vasospasm leading to cerebral ischemia and/or ischemia of extremities.

HIV protease inhibitor and strong CYP 3A4 inhibitor; rare reports of serious adverse events with ergot alkaloids including vasospasm leading to cerebral ischemia and ischemia of extremities.

Omeprazole reduces plasma levels of nelfinavir significantly (AUC decreased by 92%), which may result in loss of therapeutic effect and development of drug resistance. Concomitant use is not recommended.

Concomitant use with omeprazole and sodium bicarbonate is contraindicated. Decreased exposure may reduce antiviral effect and promote drug resistance.

Concomitant use not recommended. Pantoprazole substantially decreases nelfinavir plasma concentrations, resulting in loss of therapeutic effect and development of drug resistance.

Co-administration is not recommended. Pantoprazole substantially decreases nelfinavir plasma concentrations, resulting in loss of therapeutic effect and development of drug resistance.

( 7.2 ) 7.1 Effects of Other Drugs on Ranolazine Strong CYP3A Inhibitors Do not use ranolazine with strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir [see Contraindications (4) , Clinical Pharmacology (12.3) ].

Strong CYP3A4 inhibitor (HIV protease inhibitor) that increases simvastatin exposure and risk of myopathy and rhabdomyolysis. Concomitant use is contraindicated.

Strong CYP3A inhibitor; concomitant use not recommended due to increased suvorexant exposure.

Increased tacrolimus concentrations via CYP3A inhibition; avoid concomitant use.

Strong CYP3A inhibitor that substantially increases ticagrelor exposure, increasing risk of dyspnea, bleeding, and other adverse events.

Strong CYP3A4 inhibitor that may increase DM1 exposure and toxicity. Concomitant use should be avoided or KADCYLA treatment delayed.

No drug interaction studies have been conducted with amlodipine besylate and atorvastatin calcium and other drugs, although studies have been conducted in the individual amlodipine and atorvastatin components, as described below: Amlodipine Increased Risk of Myopathy and Rhabdomyolysis ( 2 , 5.1 , 7.3 , 12.3 ) Cyclosporine, tipranavir plus ritonavir, glecaprevir plus pibrentasvir Avoid atorvastatin Clarithromycin, itraconazole, saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir,letermovir Do not exceed 20 mg atorvastatin daily Nelfinavir Do not exceed 40 mg atorvastatin daily Lopinavir plus ritonavir, simeprevir, fibric acid derivatives, erythromycin, azole antifungals, lipid-modifying doses of niacin, colchicine Consider the risk/benefit of concomitant use with atorvastatin Other Lipid-Lowering Medications: Increased risk of myopathy (7) . In patients taking nelfinavir, do not exceed atorvastatin 40 mg [see Dosage and Administration ( 2 )].Consider the risk/benefit of concomitant use of ledipasvir plus sofosbuvir with atorvastatin. Examples: Tipranavir plus ritonavir, glecaprevir plus pibrentasvir, lopinavir plus ritonavir, simeprevir, saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir, letermovir, nelfinavir, and ledipasvir plus sofosbuvir.

Intervention Avoid concomitant use of aprepitant Examples Moderate inhibitor: diltiazem Strong inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of aprepitant [see Clinical Pharmacology ( 12.3 )].

Significantly increases atorvastatin plasma levels. Do not exceed ATORVALIQ 40 mg.

Drug Interactions Associated with Increased Risk of Myopathy/Rhabdomyolysis ( 2.6 , 5.1 , 7 , 12.3 ) Interacting Agents Prescribing Recommendations Cyclosporine, HIV protease inhibitors (tipranavir plus ritonavir), hepatitis C protease inhibitor (telaprevir) Avoid atorvastatin HIV protease inhibitor (lopinavir plus ritonavir) Use with caution and lowest dose necessary Clarithromycin, itraconazole, HIV protease inhibitors (saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir) Do not exceed 20 mg atorvastatin daily HIV protease inhibitor (nelfinavir) Hepatitis C protease inhibitor (boceprevir) Do not exceed 40 mg atorvastatin daily • Other Lipid-Lowering Medications: Use with fibrate products or lipid-modifying doses (≥ 1 g/day) of niacin increases the risk of adverse skeletal muscle effects. In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, the dose of atorvastatin should not exceed 40 mg and close clinical monitoring is recommended.

Strong CYP3A inhibitor may increase plasma concentrations of cabazitaxel. Avoid coadministration or consider 25% dose reduction.

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 ( 12.3 )] .

Darifenacin systemic exposure is increased with potent CYP3A4 inhibitors; daily dose should not exceed 7.5 mg when co-administered with nelfinavir.

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. Nelfinavir : Avoid concomitant use with dexlansoprazole. See prescribing information for nelfinavir.

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).

Avoid co-administering erlotinib tablets 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).

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) ]. Nelfinavir : Avoid concomitant use with esomeprazole sodium. See prescribing information for nelfinavir.

Strong CYP3A4 inhibitor expected to increase eszopiclone exposure and effects similarly to ketoconazole. Dose reduction needed.

Intervention Avoid concomitant use of fosaprepitant Examples Moderate inhibitor: diltiazemStrong inhibitors:ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of fosaprepitant [see Clinical Pharmacology (12.3) ] .

Intervention Avoid concomitant use of FOCINVEZ Examples Moderate inhibitor: diltiazem Strong inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of FOCINVEZ [see Clinical Pharmacology (12.3)] .

Strong CYP3A4 inhibitor may cause increased plasma concentration of triamcinolone acetonide and adverse reactions.

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. Nelfinavir : Avoid concomitant use with Lansoprazole. See prescribing information for nelfinavir.

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. Nelfinavir : Avoid concomitant use with lansoprazole. See prescribing information for nelfinavir.

Strong CYP3A4 inhibitor may increase plasma concentration of triamcinolone leading to adverse reactions.

Potent CYP3A4 inhibitor may cause intense and prolonged sedation and respiratory depression due to decreased midazolam plasma clearance.

Strong CYP3A inhibitor may increase mifepristone plasma concentrations; limit mifepristone dose to 900 mg per day when used together.

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology ( 12.3 )]. N elfinavir: Avoid concomitant use with naproxen and esomeprazole magnesium delayed-release tablets.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

Strong CYP3A4 inhibitor that significantly increases nimodipine plasma concentration and blood pressure lowering effect. Concomitant administration should generally be avoided.

Nelfinavir decreases plasma concentrations of estrogen and progestin, potentially reducing contraceptive effectiveness.

HIV protease inhibitor that may significantly decrease plasma concentrations of norethindrone and ethinyl estradiol, potentially diminishing contraceptive effectiveness.

HIV protease inhibitor that may decrease plasma concentrations of estrogen and/or progestin, potentially reducing contraceptive effectiveness.

• 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 )]. Nelfinavir : Avoid concomitant use with PRILOSEC. See prescribing information for nelfinavir.

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) ]. Avoid concomitant use of TALICIA with amprenavir, indinavir, lopinavir/ritonavir, saquinavir/ritonavir, ritonavir, tipranavir/ritonavir, fosamprenavir/ritonavir, or nelfinavir [see Warnings and Precautions (5.7) ] .

Avoid concomitant use of strong CYP3A inhibitors (e.g., clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and voriconazole).

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. Nelfinavir: Avoid concomitant use with pantoprazole sodium. See prescribing information for nelfinavir.

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. Nelfinavir: Avoid concomitant use with pantoprazole. See prescribing information for nelfinavir.

• 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. Nelfinavir : Avoid concomitant use with pantoprazole sodium in 0.9% sodium chloride injection See prescribing information for nelfinavir.

Strong CYP3A inhibitor increases paricalcitol exposure. Dose adjustment may be necessary; monitor intact PTH and serum calcium closely.

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. Nelfinavir: Avoid concomitant use with rabeprazole sodium delayed-release tablets. See prescribing information for nelfinavir.

• 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. Nelfinavir : Avoid concomitant use with rabeprazole sodium delayed-release tablets. See prescribing information for nelfinavir.

Strong CYP3A4 inhibitor may increase salmeterol exposure and risk of cardiovascular effects.

Strong CYP3A4/5 inhibitor anticipated to significantly increase saxagliptin plasma concentrations. Limit saxagliptin dosage to 2.5 mg.

Strong CYP3A4/5 inhibitor anticipated to significantly increase saxagliptin plasma concentrations. Dose limitation required.

Strong CYP3A Inhibitors : Protease inhibitors (e.g., nelfinavir, telaprevir, boceprevir, ritonavir), azole antifungals (e.g., voriconazole, posaconazole, itraconazole, ketoconazole), antibiotics (e.g., clarithromycin, troleandomycin, chloramphenicol), nefazodone, letermovir, Schisandra sphenanthera extracts May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation).

Strong CYP3A4 inhibitor that increases toremifene steady-state concentration and should be avoided.

Avoid using strong CYP3A inhibitors (e.g., oral ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, indinavir, lopinavir, ritonavir, boceprevir, nelfinavir, saquinavir, telaprevir, nefazodone, conivaptan) in patients taking YONDELIS.

Strong CYP3A4 inhibitor may increase triamcinolone plasma concentration and adverse reactions.

P-glycoprotein inhibitor that increases afatinib exposure. Reduce GILOTRIF dose by 10 mg per day if not tolerated.

Caution should be exercised when considering the co-administration of AIRSUPRA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.11) ] .

Co-administration increases azithromycin serum concentrations. Close monitoring for adverse reactions including liver enzyme abnormalities and hearing impairment is warranted.

Co-administration increases azithromycin serum concentrations. Close monitoring for liver enzyme abnormalities and hearing impairment is warranted.

Co-administration increases azithromycin serum concentrations. Close monitoring for adverse reactions such as liver enzyme abnormalities and hearing impairment is warranted.

Caution should be exercised when considering the co-administration of PULMICORT FLEXHALER with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.7) ] .

Caution should be exercised when considering the coadministration of BREYNA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.9) ] .

Caution should be exercised when considering the coadministration of budesonide inhalation suspension with long- term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions ( 5.12 ), Clinical Pharmacology ( 12.3 )].

CYP3A4 inhibitor may alter serum levels of calcifediol by inhibiting vitamin D metabolism enzymes. Dose adjustment and monitoring of serum 25-hydroxyvitamin D, PTH, and calcium may be required.

HIV protease inhibitor that inhibits CYP3A4 and may increase cyclosporine concentrations. Care should be exercised; dosage monitoring required.

Potent CYP3A4 inhibitor; darifenacin daily dose should not exceed 7.5 mg when co-administered.

HIV protease inhibitor that may decrease plasma concentrations of estrogen and/or progestin, potentially diminishing contraceptive effectiveness.

Caution should be exercised when concomitantly administering CARDURA XL with a strong CYP 3A4 inhibitor, such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole [see Clinical Pharmacology (12.3) ] .

CYP3A4 inhibitor that may increase plasma concentrations of estrogens and result in side effects.

HIV protease inhibitor that may decrease plasma concentrations of etonogestrel.

7.10 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).

7.10 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).

Caution should be exercised when considering the coadministration of budesonide and formoterol fumarate dihydrate with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.9) ] .

May decrease phenytoin serum levels; dose adjustment may be required.

Caution is recommended when administering imatinib mesylate tablets with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole).

Nelfinavir, an HIV protease inhibitor, may significantly decrease plasma concentrations of estrogen and/or progestin.

HIV protease inhibitor may significantly decrease plasma concentrations of estrogen and/or progestin.

HIV protease inhibitor that may decrease plasma concentrations of estrogen and/or progestin.

Co-administration increases nelfinavir and M8 metabolite concentrations while decreasing lopinavir. KALETRA once daily with nelfinavir is not recommended.

Caution should be exercised when considering the co-administration of mometasone furoate nasal spray with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Clinical Pharmacology (12.3) ] .

Caution should be exercised when considering the coadministration of ASMANEX HFA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3) ] .

Caution should be exercised when considering the coadministration of DULERA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.8) and Clinical Pharmacology (12.3) ] .

Caution should be exercised when considering the coadministration of mometasone furoate monohydrate nasal spray with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Clinical Pharmacology (12.3) ] .

HIV protease inhibitor that may decrease plasma concentrations of estrogen and/or progestin.

Significant decrease in systemic concentrations of norethindrone may occur.

HIV protease inhibitor that may decrease plasma concentrations of estrogen and/or progestin.

HIV protease inhibitor may significantly decrease plasma concentrations of estrogen and/or progestin.

Caution should be exercised when paclitaxel is concomitantly administered with known substrates (e.g., midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, and triazolam), inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin), and inducers (e.g., rifampin and carbamazepine) of CYP3A4. Potential interactions between paclitaxel, a substrate of CYP3A4, and protease inhibitors (ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated in clinical trials.

May decrease phenytoin serum levels; monitoring of phenytoin levels recommended.

May decrease phenytoin serum levels; monitoring of phenytoin levels recommended.

Strong CYP3A4 inhibitor that may increase midostaurin concentrations and risk of toxicity. Monitor for increased adverse reactions, especially during first week of administration.

MYTESI administration did not have a clinically relevant interaction with nelfinavir in a drug-drug interaction trial.

Other potent inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir and telithromycin) would be expected to have similar effects.

Examples: efavirenz, nevirapine, etravirine, delavirdine Antiretrovirals: Protease inhibitors (PIs) Clinical Impact: Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetic and no significant pharmacodynamic effects.

Examples: efavirenz, nevirapine, etravirine, delavirdine Antiretrovirals: Protease inhibitors (PIs) Clinical Impact: Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetic and no significant pharmacodynamic effects.

Intervention: Patients who are on chronic buprenorphine sublingual tablets treatment should have their dose monitored if NNRTIs are added to their treatment regimen Examples: Efavirenz, nevirapine, etravirine, delavirdine Antiretrovirals: Protease inhibitors (PIs) Clinical Impact: Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetic and no significant pharmacodynamic effects.

Antiretrovirals: Protease inhibitors (PIs) Clinical Impact: Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetic and no significant pharmacodynamic effects.

Examples: efavirenz, nevirapine, etravirine, delavirdine Antiretrovirals: Protease inhibitors (PIs) Clinical Impact: Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetic and no significant pharmacodynamic effects.

In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, and fluvoxamine as well as nelfinavir, ritonavir, and efavirenz inhibit the hydroxylation of bupropion.

7.5 Drugs Without Clinically Significant Interactions with Efavirenz No dosage adjustment is recommended when efavirenz is given with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, lorazepam, nelfinavir, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), paroxetine, and raltegravir.

Human immunodeficiency virus (HIV) / Hepatitis C Virus (HCV) protease inhibitors and non­-nucleoside reverse transcriptase inhibitors Significant changes in the plasma concentrations of the estrogen and /or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir]) /HCV protease inhibitors (decrease [e.g., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., efavirenz, nevirapine] or increase [e.g., etravirine]).

Human immunodeficiency virus (HIV) / Hepatitis C Virus (HCV) protease inhibitors and nonnucleoside reverse transcriptase inhibitors Significant changes in the plasma concentrations of the estrogen and /or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir]) /HCV protease inhibitors (decrease [e.g., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., efavirenz, nevirapine] or increase [e.g., etravirine]).

nelfinavir (without ritonavir) ritonavir saquinavir/ritonavir tipranavir/ritonavir ↑ nelfinavir ↓ etravirine ↓ etravirine ↓ etravirine Concomitant use of etravirine tablets with nelfinavir without low- dose ritonavir may cause a significant alteration in the plasma concentration of nelfinavir. Co- administration of etravirine tablets and nelfinavir without low- dose ritonavir is not recommended. nelfinavir (without ritonavir) ritonavir saquinavir/ritonavir tipranavir/ritonavir ↑ nelfinavir ↓ etravirine ↓ etravirine ↓ etravirine Concomitant use of etravirine tablets with nelfinavir without low- dose ritonavir may cause a significant alteration in the plasma concentration of nelfinavir.

Fosamprenavir calcium/ritonavir: ↓ Atazanavir ↔ Amprenavir HIV protease inhibitors: Indinavir a , nelfinavir a Fosamprenavir calcium: ↑ Amprenavir Effect on indinavir and nelfinavir is not well established.

Co-administration of other strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin, cobicistat-containing products) with triamcinolone acetonide injectable suspension may cause increased plasma concentration of triamcinolone leading to adverse reactions (see ADVERSE REACTIONS ).

Paradoxical Effects of Antiretroviral Agents on Methadone Hydrochloride Tablets Concurrent use of certain antiretroviral agents with CYP3A4 inhibitory activity, alone and in combination, such as abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, and tipranavir+ritonavir, has resulted in increased clearance or decreased plasma levels of methadone.

Paradoxical Effects of Anti-Retroviral Agents on Methadone Concurrent use of certain protease inhibitors with CYP3A4 inhibitory activity, alone and in combination, such as abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, and tipranvir+ritonavir, has resulted in increased clearance or decreased plasma levels of methadone.

7 DRUG INTERACTIONS • Coadministration of VIRACEPT with other drugs ( CYP3A substrates) can alter the concentration of these other drugs , and other drugs (inhibitors and/or inducers of CYP3A or CYP2C19) may alter the concentrations of nelfinavir. The potential drug-drug concentrations must be considered prior to and during therapy ( 4 , 7 , 12.3 ) • VIRACEPT should be given with food one hour after or more than 2 hours before didanosine ( 7 ) 7.1 Potential for VIRACEPT to Affect Other Drugs Nelfinavir is an inhibitor of CYP3A. 7.2 Potential for Other Drugs to Affect VIRACEPT Nelfinavir is metabolized by CYP3A and CYP2C19.

Nelfinavir* ↓Nelfinavir M8 Metabolite ↓Nelfinavir Cmin The appropriate doses of the combination of nevirapine and nelfinavir with respect to safety and efficacy have not been established.

Nelfinavir 1250 mg twice a day for 7-8 days 150 mg once a day for 8 days HIV infected patients (11) ↑ AUC by 83%, e ↑ C max by 19% Reduce rifabutin dose by 50% (to 150 mg once a day) and increase the nelfinavir dose to 1250 mg twice a day.

Unboosted PIs (atazanavir, fosamprenavir, indinavir, nelfinavir) ↑ rilpivirine ↔ unboosted PI Concomitant use of rilpivirine tablets with unboosted PIs may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes).

Unboosted PIs (atazanavir, fosamprenavir, indinavir, nelfinavir) ↑ rilpivirine ↔ unboosted PI Concomitant use of EDURANT or EDURANT PED with unboosted PIs may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes).

Human Immunodeficiency Virus (HIV)/ Hepatitis C Virus (HCV) Protease Inhibitors and Non-nucleoside Reverse Transcriptase Inhibitors : Significant decreases in systemic exposure of estrogen and/or progestin have been noted when CHCs are co-administered with some HIV protease inhibitors (eg, nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some HCV protease inhibitors (eg, boceprevir and telaprevir), and some non-nucleoside reverse transcriptase inhibitors (eg, nevirapine).

Nelfinavir Other Antiretroviral Drugs See the prescribing information of other antiretroviral drugs dependent on gastric pH for absorption prior to concomitant use with VOQUEZNA TRIPLE PAK. Nelfinavir Other Antiretroviral Drugs See the prescribing information of other antiretroviral drugs dependent on gastric pH for absorption prior to concomitant use with VOQUEZNA DUAL PAK.

Table 2: Examples of CYP450 Interactions with Warfarin Enzyme Inhibitors Inducers CYP2C9 amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast aprepitant, bosentan, carbamazepine, phenobarbital, rifampin CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking CYP3A4 alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, nilotinib, oral contraceptives, posaconazole, ranitidine, ranolazine, ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide 7.3 Drugs that Increase Bleeding Risk Examples of drugs known to increase the risk of bleeding are presented in Table 3.

Table 2: Examples of CYP450 Interactions with Warfarin Enzyme Inhibitors Inducers CYP2C9 amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast aprepitant, bosentan, carbamazepine, phenobarbital, rifampin CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking CYP3A4 alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, nilotinib, oral contraceptives, posaconazole, ranitidine, ranolazine, ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide 7.3 Drugs that Increase Bleeding Risk Examples of drugs known to increase the risk of bleeding are presented in Table 3 .