Rifabutin Atovaquone

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. 

Atovaquone (Mepron) [Antiprotozoal] Uses Rx prevention PCP Action 4- nucleic acid ATP synth Dose Rx 750 mg PO bid for 21 d Prevention 1500 mg PO once/d (w/ meals) Caution [C, ] Disp Susp SE FevCT, HA, anxiety, insomnia, rash, N/V Interactions X Effects W/ metoclopramide, rifabutin, rifampin, tetracycline EMS None OD Sxs unknown but may cause a rash symptomatic and supportive... 

Fluconazole, probenecid and atovaquone increase the risk of myelotoxicity by zidovudine. This may be attributed to an increased plasma concentration of zidovudine in the presence of these drugs, perhaps through their inhibitory effects on glucuronose transferase. Rifabutin and rifampin decrease plasma concentrations, and clarithromycin decreases the absorption of zidovudine. Zidovudine and stavu-dine should not be used in combination because they compete for intracellular phosphorylation. 

RIFAMYCINS ANTIMALARIALS -ATOVAQUONE Both rifampicin and rifabutin L atovaquone levels, although the effect is greater with rifampicin (1AUC 50% cf. with 34% rifabutin) Uncertain because atovaquone is predominantly excreted unchanged via the gastrointestinal route Avoid co-administration with rifampicin. Take care with rifabutin and watch for poor response to atovaquone... 

In 24 healthy subjects given atovaquone 750 mg twice daily and rifabutin 300 mg once daily for 14 days, there was a modest 34% decrease in the AUC of atovaquone and a small 19% decrease in the rifabutin levels. ... 

Rifampicin reduces serum atovaquone levels by about 50% whereas atovaquone modestly raises serum rifampicin levels. The combination should be avoided because of the likelihood of sub-therapeutic atovaquone levels. Rifabutin caused a lesser 34% decrease in atovaquone levels, which the manufacturer considers may also reduce efficacy. 

The effect of rifabutin is less than rifampicin, and the authors of the above report suggested that no atovaquone dosage adjustment is needed. However, in the UK, the manufacturer of atovaquone still considers that rifabutin use could result in subtherapeutic atovaquone levels in some patients, and they also advise against the concurrent use of this combination. ... 

---