Lopinavir Rifampicin

Interactions. Involvement of protease inhibitors with the cytochrome P450 system provides scope for interaction with numerous substances. Agents that induce P450 enzymes (e.g. rifampicin, St John s wort) accelerate their metabolism, and reduce plasma concentration enzyme inhibitors (e.g. ketoconazole, cimetidine) raise their plasma concentration competition with other drugs for the cytochrome enzymes can lead to variable results. Ritonavir is itself a powerful inhibitor of CYP 3A4 and CYP 2D6. This effect is utilised when ritonavir in small quantity is combined (in capsules) with lopinavir to inhibit its metabolism and increase its therapeutic efficacy. The present account should be sufficient to warn the physician, and thereby the patient, to take particular heed when seeking to co-administer any drug a with protease inhibitor. 

Clinically important, potentially hazardous interactions with albendazole, aminoglutethimide, aspirin, bexarotene, carbamazepine, cyclophosphamide, dasatinib, diuretics, ephedrine, imatinib, itraconazole, lapatinib, live vaccines, lopinavir, methotrexate, phenobarbital, phenytoin, praziquantel, primidone, rifampicin, rifampin, temsirolimus, warfarin... 

Rifampicin (Rifampin). Rifampicin 600 mg daily for 10 days decreased the AUC of lopinavir (given as lopinavir/ritonavir 400/100 mg twice daily) by 75% in a study in healthy subjects. " A dose titration of lopinavir/ritonavir was earried out in healthy subjects to try and overcome the interaction with rifampicin. In 10 evaluable subjects, use of rifampicin 600 mg daily with lopinavir/ritonavir 800/200 mg twice daily decreased the minimum lopinavir level by 57% without affecting the maximum level, when compared with lopinavir/ritonavir 400/100 mg twice daily without rifampicin. In another 9 evaluable subjects, rifampicin 600 mg daily with lopinavir/ritonavir 400/400 mg twice daily did not alter the maximum or minimum level of lopinavir, but markedly increased ritonavir levels, when compared with lopinavir/ritonavir 400/100 mg twice daily without rifampicin. Of 29 subjects who received the adjusted doses of lopinavir/ritonavir with rifampicin, 9 subjects had grade 2 to 3 elevations in liver enzymes, and this was more eommon in the lopinavir/ritonavir 400/400 mg group than the lopinavir/ritonavir 800/200 mg group. 

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. 

Lopinavir + ritonavir The interaction of rifampicin with lopinavir -I- ritonavir has been assessed in 34 patients, of whom 23 took a non-adjusted dose of lopinavir + ritonavir (400/100 mg bd or 800/200 mg/ day), six took a slightly adjusted dose (500/ 125 or 533/133 mg bd), and five took a recommended dose (400/400 or 800/200 mg bd) [85 ]. Seven prematmely stopped taking the combination within 4 weeks because of acute adverse events (4/23, 1/6, and 2/5 in the three respective dosage groups). Combined use of lopinavir -I- ritonavir and rifampicin is challenging, as it implies a balance between suboptimal efficacy and toxicity. 

L homme RF, Nijland HM, Gras L, Aamoutse RE, van Crevel R, Boeree M, Brinkman K, Prins JM, Juttmann JR, Burger DM. Clinical experience with the combined use of lopinavir/ritonavir and rifampicin. AIDS 2009 23(7) 863-5. 

Murphy RA, Marconi VC, Gandhi RT, Kuritzkes DR, Sunpath H. Coadministration of lopinavir/ritonavir and rifampicin in HIV and tuberculosis co-infected adults in South Africa. PLoS One 2012 7(9) e44793. 

---