Rifampicin ritonavir + saquinavir

Clinically important, potentially hazardous interactions with atazanavir, carbamazepine, clarithromycin, dexamethasone, erythromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, phenobarbital, phenytoin, rifampicin, ritonavir, saquinavir, St John s wort... 

N/V/D, abcl pain, bleeding, fever, T QT Interactions T Effects W/ atazanavir, clar-itliromycin, erythromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfi-navir, ritonavir, saquinavir, telithromydn 1 effects W/ antacids, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampicin, St. John s wort EMS Ding contains lactose, may cause D/abd discomfort in pts w/ lactose intolerance OD Sxs unknown symptomatic and supportive... 

However, Roche Pharma have recommended that rifampicin should not be used in patients who are taking ritonavir + saquinavir, because of the results of a study in which 11 of 28 patients who took rifampicin 300 mg/day with ritonavir 100 mg bd + saquiniavir 1000 mg bd developed severe hepatotoxicity [http //www.fda.gov/medwatch/ safety/2005/Saquinavir-Rifampin deardoc Feb05]. 

Rifampicin (Rifampin). Rifampicin 600 mg once daily decreased the AUC of saquinavir (soft capsules) 1.2 g three times daily by 70%. It was suggested that the combination of ritonavir and saquinavir (both 400 mg twice daily) could cancel out the effects of rifampicin on saquinavir, so therapeutic levels of all three drugs could be achieved. This assumption has been confirmed in HIV-positive patients. Five of 20 patients originally given the combination developed hepatotoxicity, 2 of whom had co-morbidities. However, in a further study in healthy subjects, severe hepatotoxicity with transaminase elevations of about 20 times the upper limit of normal occurred in 11 of 17 subjects after they took saquina-vir/ritonavir 1000/100 mg twice daily with rifampicin 600 mg once daily for 1 to 5 days. > ... 

VeldkampAI,HoetelmansRMW,BeijnenJH, Mulder JW,Meenhorst PL. Ritonavir enables combined therapy with rifampicin and saquinavir. Clin Infect Dis (1999) 29,1586. 

Ritonavir + saquinavir The effects of rifampicin 600 mg/day on the steady-state... 

F is 3 X hoger) ritonavir (600 mg daily or two or three times per week) is a possibility. However, the pharmacokinetic data and clinical experience for these combinations are limited. Coadministration of saquinavir HGC or saquinavir SGC with rifampicin (in the absence of ritonavir) is not recommended because rifampicin markedly decreases concentration of saquinavir... 

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... 

In 14 healthy men, rifampicin 600 mg/day reduced the AUC of saquinavir (given as a soft gel capsule 1200 mg tds) by 46% when both were given for 14 days this reduction can be counteracted by the addition of ritonavir (18). 

Rifampicin (rifampin) bioavaiiabiiity is increased by indinavir, but amprenavir has no effect. Rifampicin markedly reduces the bioavailability of amprenavir, atazanavir/ritonavir, indinavir, indinavir with ritonavir, iopinavir/ritonavir, nelfinavir and saquinavir, but oniy modestiy reduces that of ritonavir. The effects of rifampicin on iopinavir/ritonavir and saquinavir/ritona-vir can be overcome by increasing the protease inhibitor dose, but this appears to increase adverse effects (hepatotoxicity). 

Rifampicin markedly reduces the levels of many of the protease inhibitors, and its use with unboosted protease inhibitors should be avoided, because of the risk of reduced antiviral efficacy and emergence of resistant viral strains. There are limited data to suggest that ritonavir as the sole protease inhibitor, or ritonavir used as a pharmacokinetic enhancer with other protease inhibitors such as saquinavir, can be used with rifampicin. However, further study has shown a high incidence of hepatotoxicity with saquinavir/ritonavir 1000/100 mg twice daily and rifampicin, and the manufacturers of ritonavir and saquinavir advise that these drugs should not be given together with rifampicin. Current UK guidelines state that, until more data are available, ritonavir-boosted protease inhibi-... 

Saquinavir/ritonavir Rifabutin dose reduced by at least 75% (150 mg every other day or three times per week). Appropriate saquinavir/ritonavir dose not established. Consider usual dose (1000/100 mg twice daily). Rifampicin dose unchanged. Saquinavir/ritonavir 400/400 mg twice daily. Note that a regimen of 1000/100 mg twice daily with rifampicin was associated with severe hepatotoxicity, and the combination is contraindicated. 3,20,21... 

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