Protease inhibitors 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. 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

Atovaquone modestly reduces the minimum ievei of indinavir. Ritonavir aione and ritonavir-boosted protease inhibitors are predicted to decrease atovaquone ieveis. 

The manufacturer of ritonavir predicts that it will decrease the plasma levels of atovaquone, - by inducing atovaquone glucuronidation. They say that the clinical significance of this prediction is unknown, but that an increase in the atovaquone dose might be needed. Careful monitoring of serum levels and/or therapeutic effects is recommended when atovaquone is given with ritonavir as a pharmacokinetic enhancer or as an antiretroviral. This predicted interaction would therefore apply to lopinavir/ritonavir and any other boosted protease inhibitors. However, there does not appear to be any actual data to prove that the interaction occurs or is clinically relevant. 

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