Nevirapine

Nevirapine substantially decreases atazanavir exposure and increases nevirapine exposures. Do not co-administer.

Co-administration may cause significant decrease in plasma concentrations of etravirine and loss of therapeutic effect. Co-administration of etravirine and other NNRTIs is not recommended.

Co-administered with atazanavir; nevirapine is contraindicated with this combination due to decreased atazanavir exposure and increased nevirapine levels.

Co-administration decreases doravirine plasma concentrations. Use with nevirapine is not recommended.

Co-administration without ritonavir is not recommended due to decreased amprenavir levels and increased nevirapine exposure.

Potent CYP3A4 enzyme inducer that may decrease itraconazole bioavailability and efficacy. Avoid use 2 weeks before and during itraconazole treatment.

Potent CYP3A4 enzyme inducer that may decrease ketoconazole bioavailability and reduce antifungal efficacy. Coadministration not recommended.

Strong CYP 3A4 inducer; likely to decrease the pharmacological action of methylergonovine maleate.

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

Non-nucleoside reverse transcriptase inhibitor that may significantly decrease plasma concentrations of norethindrone and ethinyl estradiol, potentially diminishing contraceptive effectiveness.

Non-nucleoside reverse transcriptase inhibitor that may significantly decrease plasma concentrations of estrogen and/or progestin.

Plasma warfarin levels may change with potential for increases in coagulation time. Anticoagulation levels should be monitored frequently.

MRP2 inhibitor that may increase cabozantinib exposure. Monitor for increased toxicity with concomitant use.

Nevirapine is a hepatic CYP enzyme inducer expected to reduce caspofungin acetate plasma concentrations. Increased caspofungin dosing should be considered.

Nevirapine significantly decreases clarithromycin exposure while increasing 14-OH metabolite concentrations, potentially reducing activity against Mycobacterium avium complex. Alternatives like azithromycin should be considered.

Non-nucleoside reverse transcriptase inhibitor that may decrease plasma concentrations of estrogen and/or progestin, potentially diminishing contraceptive effectiveness.

CYP3A4 inducer that may reduce plasma concentrations of estrogens, possibly decreasing therapeutic effects and altering uterine bleeding profile.

Nevirapine decreases ethinyl estradiol plasma levels. Oral contraceptives should not be used as sole contraception method; alternative or additional contraception recommended.

Non-nucleoside reverse transcriptase inhibitor that may decrease plasma concentrations of etonogestrel.

Antifungals: Fluconazole* ↑Nevirapine Because of the risk of increased exposure to nevirapine, caution should be used in concomitant administration, and patients should be monitored closely for nevirapine-associated adverse events.

CYP3A4 inducer may decrease serum hydrocortisone concentrations and increase risk of adrenal crisis; may require dose increase.

Appropriate doses with respect to efficacy and safety have not been established due to decreased indinavir levels.

Nevirapine, a non-nucleoside reverse transcriptase inhibitor, may significantly decrease plasma concentrations of estrogen and/or progestin.

Non-nucleoside reverse transcriptase inhibitor may significantly decrease plasma concentrations of estrogen and/or progestin.

Non-nucleoside reverse transcriptase inhibitor that may decrease plasma concentrations of estrogen and/or progestin.

Dose adjustment to 500/125 mg tablets or 533/133 mg oral solution twice daily recommended due to decreased lopinavir exposure.

Strong CYP 3A4 inducer; likely to decrease the pharmacological action of methylergonovine.

Coadministration decreases nelfinavir concentrations. Appropriate nelfinavir dose with respect to safety and efficacy has not been established.

Non-nucleoside reverse transcriptase inhibitor that may decrease plasma concentrations of estrogen and/or progestin.

Significant decrease in systemic concentrations of norethindrone may occur.

Non-nucleoside reverse transcriptase inhibitor that may decrease plasma concentrations of estrogen and/or progestin.

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

Fosamprenavir* ↓ Amprenavir ↑ Nevirapine Co-administration of nevirapine and fosamprenavir without ritonavir is not recommended. Fosamprenavir/Ritonavir* ↓ Amprenavir ↑ Nevirapine No dosing adjustments are required when nevirapine is co-administered with 700/100 mg of fosamprenavir/ritonavir twice daily. The combination of nevirapine administered with fosamprenavir/ritonavir once daily has not been studied.

Alternatives to clarithromycin, such as azithromycin, should be considered.

Hepatitis C Antiviral Agents Boceprevir Plasma concentrations of boceprevir may be decreased due to induction of CYP3A4/5 by nevirapine. Nevirapine and boceprevir should not be coadministered because decreases in boceprevir plasma concentrations may result in a reduction in efficacy.

Anticonvulsants: Carbamazepine, clonazepam, ethosuximide Plasma concentrations of nevirapine and the anticonvulsant may be decreased.

Cancer Chemotherapy: Cyclophosphamide Plasma concentrations may be decreased.

23 Atazanavir 300/100 mg ↓ 42 (↓ 52 to ↓ 29) Atazanavir 300/100 mg ↓ 28 (↓ 40 to ↓ 14) Atazanavir 300/100 mg ↓ 72 (↓ 80 to ↓ 60) Atazanavir 400/100 mg ↓ 19 (↓ 35 to ↑ 2) Atazanavir 400/100 mg ↑ 2 (↓ 15 to ↑ 24) Atazanavir 400/100 mg ↓ 59 (↓ 73 to ↓ 40) Darunavir/Ritonavir Based on between-trial comparison.

Antiarrhythmics: Amiodarone, disopyramide, lidocaine Plasma concentrations may be decreased.

Nevirapine decreases efavirenz concentrations. No appropriate doses established for safe and effective use of this combination.

Anticonvulsants: Carbamazepine, clonazepam, ethosuximide Plasma concentrations of nevirapine and the anticonvulsant may be decreased.

Lopinavir/Ritonavir* ↓Lopinavir Dosing in adult patients: A dose adjustment of lopinavir/ritonavir to 500/125 mg tablets twice daily or 533/133 mg (6.5 mL) oral solution twice daily is recommended when used in combination with nevirapine. Neither lopinavir/ritonavir tablets nor oral solution should be administered once daily in combination with nevirapine. Neither lopinavir/ritonavir tablets nor oral solution should be administered once daily in combination with nevirapine.

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.

Calcium Channel blockers: Diltiazem, nifedipine, verapamil Plasma concentrations may be decreased.

300 mg SD 200 mg BID 8 ↑ 1 (↓ 35 to ↑ 55) ↑ 54 (↓ 6 to ↑ 151) ↔ Nelfinavir 750 mg TID 200 mg QD x 14 days; 200 mg BID x 14 days 23 ↔ ↔ ↓ 32 (↓ 50 to ↑ 5) Nelfinavir-M8 metabolite ↓ 62 (↓ 70 to ↓ 53) ↓ 59 (↓ 68 to ↓ 48) ↓ 66 (↓74 to ↓ 55) Ritonavir 600 mg BID 200 mg QD x 14 days; 200 mg BID x 14 days 18 ↔ ↔ ↔ Stavudine 30-40 mg BID 200 mg QD x 14 days; 200 mg BID x 14 days 22 ↔ ↔ § Zalcitabine 0.125-0.25 mg TID 200 mg QD x 14 days; 200 mg BID x 14 days 6 ↔ ↔ § Zidovudine 100-200 mg TID 200 mg QD x 14 days; 200 mg BID x 14 days 11 ↓ 28 (↓ 40 to ↓ 4) ↓ 30 (↓ 51 to ↑ 14) § Other Medications AUC C max C min Clarithromycin 500 mg BID 200 mg QD x 14 days; 200 mg BID x 14 days 15 ↓ 31 (↓ 38 to ↓ 24) ↓ 23 (↓ 31 to ↓ 14) ↓ 56 (↓ 70 to ↓ 36) Metabolite 14-OH-clarithromycin ↑ 42 (↑ 16 to ↑ 73) ↑ 47 (↑ 21 to ↑ 80) ↔ Ethinyl Estradiol and Norethindrone 0.035 mg (as Ortho-Novum ® 1/35) 1 mg (as Ortho-Novum ® 1/35) 200 mg QD x 14 days; 200 mg BID x 14 days 10 ↓ 20 (↓ 33 to ↓ 3) ↔ § ↓ 19 (↓ 30 to ↓ 7) ↓ 16 (↓ 27 to ↓ 3) § Depomedroxy- Progesterone Acetate 150 mg every 3 months 200 mg QD x 14 days; 200 mg BID x 14 days 32 ↔ ↔ ↔ Fluconazole 200 mg QD 200 mg QD x 14 days; 200 mg BID x 14 days 19 ↔ ↔ ↔ Ketoconazole 400 mg QD 200 mg QD x 14 days; 200 mg BID x 14 days 21 ↓ 72 (↓ 80 to ↓ 60) ↓ 44 (↓ 58 to ↓ 27) § Methadone Individual Subject Dosing 200 mg QD x 14 days; 200 mg BID ≥ 7 days 9 In a controlled pharmacokinetic trial with 9 subjects receiving chronic methadone to whom steady-state nevirapine therapy was added, the clearance of methadone was increased by 3-fold, resulting in symptoms of withdrawal, requiring dose adjustments in 10 mg segments, in 7 of the 9 subjects.

Saquinavir/Ritonavir The interaction between nevirapine and saquinavir/ritonavir has not been evaluated The appropriate doses of the combination of nevirapine and saquinavir/ritonavir with respect to safety and efficacy have not been established.

Telaprevir Plasma concentrations of telaprevir may be decreased due to induction of CYP3A4 by nevirapine and plasma concentrations of nevirapine may be increased due to inhibition of CYP3A4 by telaprevir. Nevirapine and telaprevir should not be coadministered because changes in plasma concentrations of nevirapine, telaprevir, or both may result in a reduction in telaprevir efficacy or an increase in nevirapine-associated adverse events.

No significant interaction was observed when tipranavir was co-administered with low-dose ritonavir and nevirapine.