Nevirapine Ketoconazole

Drugs that may affect atazanavir include the following antacids and buffered medications, clarithromycin, didanosine (buffered formulation only), efavirenz, H2-receptor antagonists, indinavir, itraconazole, ketoconazole, nevirapine, proton pump inhibitors, rifampin, ritonavir, St. John s wort, tenofovir, voriconazole. 

Drugs that may be affected by nevirapine include rifamycins, clarithromycin, oral contraceptives, efavirenz, ketoconazole, methadone, protease inhibitors, warfarin, zidovudine. 

Others Acetaminophen, amiodarone, carbamazepine, delavirdine, efavirenz, nevirapine, quinidine, repaglinide, sildenafil, tadalafil, trazodone, vardenafil Amiodarone, amprenavir, atazanavir, ciprofloxacin, cisapride, clarithromycin, diltiozem, erythromycin, fluconazole, fluvoxamine, grapefruit juice (in high ingestion), indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, norfloxacin, ritonavir, telithromycin, troleandomycin, verapamil, voriconazole Carbamazepine, efavirenz, glucocorticoids, macrolide antibiotics, nevirapine, phenytoin, phenobarbital, rifabutin, rifapentine, rifampin, St. John s wort... 

Nevirapine induces and is metabolized by CYP3A4 therefore, coadministration of drugs that induce or are metabolized by this isoenzyme may result in interactions. Nevirapine may decrease the effectiveness of ethinyl estradiol-based contraceptives and can lower plasma concentrations of methadone. Nevirapine should not be administered with ketoconazole, rifampin, or rifabutin. 

Nevirapine is a moderate inducer of CYP3A metabolism, resulting in decreased levels of amprenavir, indinavir, lopinavir, saquinavir, efavirenz, and methadone (Table 49-4). Drugs that induce the CYP3A system, such as tipranavir, rifampin, rifabutin, and St. John s wort, can decrease levels of nevirapine, whereas those that inhibit CYP3A activity, such as fluconazole, ketoconazole, and clarithromycin, can increase nevirapine levels. 

Nevirapine NNRTI 200 mg bid Rash, hepatitis, nausea, headache Dose-escalate from 200 mg qd over 14 days to decrease frequency of rash. Avoid concurrent use with ketoconazole, methadone, and... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

Nevirapine markedly reduces the AUC of ketoconazole. In theory, efavirenz may interact similarly, whereas delavirdine may increase ketoconazole levels. The NNRTI plasma levels may be raised by ketoconazole. 

The manufacturers of nevirapine quote a study in which nevirapine 200 mg twice daily was given with ketoconazole 400 mg daily. The ketoconazole AUC was markedly reduced by 72% and its maximum plasma levels were reduced by 44%. In addition, the nevirapine plasma levels were raised by 15 to 28% compared with historical control data. ... 

Ketoconazole is likely to inhibit the metabolism of the NNRTIs by the cytochrome P450 isoenzyme CYP3A4. Nevirapine induces the metabolism of ketoconazole by CYP3A4, and, in theory, efavirenz is likely to interact similarly, whereas delavirdine is likely to inhibit ketoconazole metabolism by CYP3A4 (see Table 21.2 , (p.773)). 

The manufacturer of nevirapine states that ketoconazole and nevirapine should not be used together, because of the likely reduced efficacy of ke-toconazole. Efavirenz might be expected to interact similarly although the manufacturer of efavirenz says that the potential for an interaction has not been studied. NNRTI levels might be raised by ketoconazole, which might increase adverse effects. Cautious monitoring of efficacy and adverse effects would be prudent if concurrent use is necessary. 

Rifampin (potent CYP3A4 inducer) Ketoconazole (strong CYP3A4 inhibitor) Isoniazid/pyrazi namide Nevirapine Kaletra (lopinavir/nton avir)... 

Class 2 (High PermeabiUty, Low Solrrbility) Azathioprine, Azithromycin, Alprazolam, Warfarin, Haloperidol, Glipizide, Griseofulvinum, Danazol, Dapsone, Diclofenac, Indometacin, Itraconzol, Carbamazepine, Carvedilol, Ketoconazole, Lansoprazol, Mebendazole, Mefloqrrine, Nalidixic acid. Nevirapine, Piroxicam, Praziquantel, Ritonavir, Rifampicinirm, Spironolactone, Tamoxifen, Terfenadine, Trimethoprim, Ibnprofen, lopanoic add, Lovastatin, Naproxen, Oxaprozin, Flubiprofen, Cisapride. ... 

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