Rifabutin Amprenavir

Amprenavir Rifabutin dose at least halved (150 mg daily or every other day, or 300 mg three times per week). Amprenavir dose unchanged. Not recommended (amprenavir levels markedly reduced). 1-3... 

Drugs that might be affected by amprenavir include antiarrhythmics, anticonvulsants, azole antifungals, benzodiazepines, calcium channel blockers, cisapride, clarithromycin, cyclosporine, ergot alkaloids, fentanyl, HMG-CoA reductase inhibitors, indinavir, methadone, nelfinavir, oral contraceptives, pimozide, rifabutin, ritonavir, saquinavir, sildenafil, tacrolimus, trazodone, tricyclic antidepressants, warfarin, and zidovudine. 

Efavirenz (Sustiva) [Antiretroviral/NNRTI] Uses Hiv infxns Action Antiretroviral nonnucleoside RTI Dose Adults. 600 mg/d PO qhs Feds. See package insert avoid high-fat meals Caution [D, ] CDC recommends HIV-infected mothers not breast-feed Contra Component sensitivity Disp Caps SE Somnolence, vivid dreams, dizziness, rash, N/V/D Interactions T Effects W/ ritonavir T effects OF CNS depressants, ergot derivatives, midazolam, ritonavir, simvastatin, triazolam, warfarin X effects W/ carbamazepine, phenobarbital, rifabutin, rifampin, saquinavir, St. John s wort i effects OF amprenavir, carbamazepine, clarithromycin, indinavir, phenobarbital, saquinavir, warfarin may alter effectiveness OF OCPs EMS Concurrent EtOH usage can t CNS d ression OD May cause muscle contractions and adverse CNS effects activated charcoal may be effective... 

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... 

Dosage adjustments in comhination therapy Amprenavir. Amprenavir 1,200 mg and ritonavir 200 mg once a day or amprenavir 600 mg and ritonavir 100 mg twice a day. Am-penavirandefavirenz. Amprenavir 1,200 mg twice a day and ritonavir 200 mg twice a day with standard dose of efavirenz. Indinavir. Indinavir 800 mg twice a day and ritonavir 100-200 mg twice a day or indinavir400 mg twice a day and ritonavir 400 mg twice a day. Nelfinavirorsaquinavir. Ritonavir 400 mg twice a day. Rifabutin. Decrease rifabutin dosage to 150 mg every other day. 

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. 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

The drugs that induce cytochrome P-450 system isoenzyme CYP3A4 will inhibit the blood levels of amprenavir. It decreases the plasma levels of methadone and delavirdine and increases the plasma levels of rifabutin, ketoconazole and atorvas-tatin. This may be the result of the ability of amprenavir to inhibit as well as induce CYP3A4. 

RIFABUTIN PROTEASE INHIBITORS t efficacy and t adverse effects of rifabutin Inhibition of CYP3A4-mediated metabolism. Nelfinavir also competitively inhibits 2C19 1 rifabutin dose by at least 50% when given with amprenavir, indinavir or nelfinavir, and by 75% with atazanavir, ritonavir (with or without lopinavir) or tipranavir... 

The adverse effects of amprenavir in patients treated with combination therapy included nausea, vomiting, diarrhea, epigastric pain, flatulence, paresthesia, headache, rash, and fatigue (4). The contribution of a single drug to the observed adverse effects is difficult to establish. Amprenavir inhibits CYP3A4 to a greater extent than saquinavir, and to a much lesser extent than ritonavir (5). Co-administration with rifampicin and rifabutin should be avoided. Those who take... 

Co-administration of amprenavir with rifampicin and rifabutin should be avoided (12). 

Polk RE, Brophy DF, Israel DS, Patron R, Sadler BM, Chittick GE, Symonds WT, Lou Y, Kristoff D, Stein DS. Pharmacokinetic interaction between amprenavir and rifabutin or rifampin in healthy males. Antimicrob Agents Chemother 2001 45(2) 502-8. 

The use of rifampicin with the protease inhibitors indinavir, nelfinavir, and amprenavir is contraindicated. However, these agents can be used with rifabutin after appropriate dosage reduction. Failure to reduce the dosage of rifabutin can result in toxic manifestations, such arthralgia and uveitis. 

Clinically important, potentially hazardous interactions with abarelix, acenocoumarol, amisulpride, amprenavir, anisindione, anticoagulants, arsenic, astemizole, carbimazole, celiprolol, ciprofloxacin, dabigatran, degarelix, dicumarol, digoxin, diltiazem, enoxacin, fentanyl, fosamprenavir, gatifloxacin, grapefruit juice, lomefloxacin, methotrexate, moxifloxacin, nilotinib, norfloxacin, ofloxacin, oxprenolol, quinidine, quinolones, rifabutin, rifampin, rifapentine, ritonavir, simvastatin, sparfloxacin, sulpiride, tacrolimus, tipranavir, verapamil, warfarin, zuclopenthixol... 

Clinically important, potentially hazardous interactions with adefovir, alprazolam, amprenavir, anisindione, anticoagulants, buprenorphine, carbamazepine, dicumarol, dihydroergotamine, ergot, fosamprenavir, indinavir, ixabepilone, lovastatin, methadone, methysergide, midazolam, phenobarbital, phenytoin, quinidine, rifabutin, rifampin, sildenafil, simvastatin, triazolam, warfarin... 

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... 

Clinically important, potentially hazardous interactions with alfentanil, alfuzosin, alprazolam, amiodarone, amprenavir, aprepitant, astemizole, atazanavir, bepridil, buprenorphine, bupropion, carbamazepine, chlordiazepoxide, ciclesonide, clozapine, conivaptan, cyclosporine, cyproterone, dasatinib, diazepam, dihydroergotamine, ergot alkaloids, estazolam, eszopidone, etravirine, ezetimibe, fentanyl, fesoterodine, flecainide, flurazepam, fluticasone, halazepam, ivabradine, ixabepilone, ketoconazole, lapatinib, levothyroxine, meperidine, meptazinol, methysergide, midazolam, nifedipine, nilotinib, oral contraceptives, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quazepam, quinidine, ranolazine, rifabutin, rifampin, rifapentine, rimonabant, rivaroxaban, saquinavir, sildenafil, silodosin, simvastatin, solifenacin, St John s wort, tadalafil, temsirolimus, trabectedin, triazolam, vardenafil, voriconazole, zolpidem... 

Rifabutin bioavailability is increased by amprenavir, atazanavir, fosamprenavir/ritonavir, indinavir, lopinavir/ritonavir, nelfinavir, tipranavir/ritonavir, and especially ritonavir, with an increased risk of toxicity. Rifabutin modestiy decreases the bioavailability of indinavir, neifinavir, and particuiarly saquinavir (with an increased risk of therapeutic faiiure), but has no effect on amprenavir, atazanavir, and ritonavir-boosted fosamprenavir. The combination of rifabutin with protease inhibitors may be used, but dosage adjustments of rifabutin or both drugs are often necessary. 

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