Rifabutin Lopinavir

Drugs that might decrease plasma concentrations of lopinavir/ritonavir include rifampin, phenobarbital, carbamazepine, phenytoin, azole antifungals, delavirdine, rifabutin, St. John s wort, efavirenz, nevirapine, and corticosteroids. 

Drugs that might be affected by lopinavir/ritonavir include ergot derivatives, oral contraceptives, antiarrhythmics, HMG-CoA reductase inhibitors, HIV protease inhibitors, atovaquone, calcium channel blockers, ketoconazole, itraconazole, pimozide, cisapride, clarithromycin, disulfiram, metronidazole, immunosuppressants, midazolam, triazolam, narcotic analgesics, rifabutin and rifabutin metabolite, sildenafil, warfarin, bupropion, clozapine, desipramine, piroxicam, quinidine, theophylline, and zolpidem. 

HIV infection (in combination with other antiretrovirals) PO 800 mg (two 400-mg capsules) q8h. Dosage adjustments when given concomitantly Delavirdine, itraconazole, ketoconazok Reduce dose to 600 mg q8h. Efavirenz-. Increase dose to 1,000 mg q8h. Lopinavir/ritonavir Reduce dose to 600 mg twice a day. Nevirapine-. Increase dose to 1,000 mgqSh. Rifabutin-. Reduce rifabutin by lA and increase indinavir to 1,000 mg q8h. Ritonavir 100-200 mg twice a day and indinavir 800 mg twice a day or ritonavir 400 mg twice a day and indinavir 400 mg twice a 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... 

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... 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Clinically important, potentially hazardous interactions with amiodarone, atorvastatin, bepridil, carbamazepine, delavirdine, dihydroergotamine, etravirine, flecainide, itraconazole, ketoconazole, lidocaine, lopinavir, lovastatin, midazolam, phenobarbital, phenytoin, pimozide, propafenone, quinidine, rifabutin, rifampin, sildenafil, simvastatin, St John s wort, triazolam, vardenafil, 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... 

Rifabutin 300 to 600 mg daily for 12 days did not significantly affect the pharmacokinetics of [buffered] didanosine 167 to 250 mg twice daily in 12 patients with AIDS. The steady-state pharmacokinetics of rifabutin were not affected by didanosine (buffered sachet preparation), which suggests that the buffer used in the didanosine preparation had no effect on rifabutin absorption. However, a case has been reported of a patient taking lopinavir/ritonavir, efavirenz, lamivudine and buffered didanosine who had impaired rifabutin absorption. When rifabutin was taken 30 minutes after didanosine, rifabutin levels were undetectable, but when rifabutin was taken 3 hours after didanosine, rifabutin levels were apparent. ... 

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. 

Rifabutin. When healthy subjects were given lopinavir/ritonavir 400/100 mg twice daily with rifabutin 150 or 300 mg daily for 10 days the AUC of rifabutin was increased threefold and the AUC of lopinavir was increased by 17%. " ... 

Lopinavir/ritonavir Rifabutin dose reduced by at least 75% (150 mg every other day or three times per week). Lopinavir/ritonavir dose unchanged. Not recommended (lopinavir leveb markedly reduced). However, adjusted doses of lopinavir/ritonavir (800/200 mg or 400/400 mg twice daily) may overcome the pharmacokinetic interaction, but have a high incidence of elevated liver enzymes, and so if used, close monitoring is needed. 3, 17-19... 

Drug-drug interactious Lopinavir - - ritonavir The steady-state pharmacokinetics of rifabutin and its active metabolite 25-desacetyl-rifabutin have been examined before and after the addition of lopinavir - -ritonavir in 10 patients with HIV infection and active tuberculosis [79 ]. Samples were collected at 2-4 weeks after starting rifabutin 300 mg thrice weekly without lopinavir -I- ritonavir, 2 weeks after the addition of lopinavir -I- ritonavir 400/100 mg bd to rifabutin 150 mg thrice weekly, and (if rifabutin plasma concentrations were below the target range) 2 weeks after an increase in rifabutin dosage to 300 mg thrice weekly with lopinavir + ritonavir. Lopinavir - -ritonavir reduced the Cmax of total rifabutin and most unbound rifabutin C ax values were below the tuberculosis MIC. For most patients, the AUC was low or lower than associated with treatment failure or relapse and with acquired rifampicin resistance. The authors concluded that the recommended doses of rifabutin for use with lopinavir -I- ritonavir may be inadequate in many patients and recommended monitoring of plasma concentrations. 

Boulanger C, Hollender E, Farrell K, Stambaugh JJ, Maasen D, Ashkin D, Symes S, Espinoza LA, Rivero RO, Graham JJ, Peloquin CA. Pharmacokinetic evaluation of rifabutin in combination with lopinavir-ritonavir in patients with HIV infection and active tuberculosis. Clin Infect Dis 2009 49(9) 1305-11. 

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