Fosamprenavir Antacids

Drugs that may affect fosamprenavir include antacids, carbamazepine, delavirdine, dexamethasone, histamine H2-receptor antagonists, HMG-CoA reductase inhibitors,... 

Delavirdine NNRTI 400 mg tid Separate dosing from ddl or antacids by 1 h Rash, t liver enzymes, headache, nausea, diarrhea See footnote 4 for contraindicated medications. Also avoid concurrent fosamprenavir and rifabutin. Teratogenic in rats... 

Fosamprenavir PI2 1400 mg bid or 700 mg bid with ritonavir 100 bid or 1400 mg daily with ritonavir 100-200 mg daily. Adjust dose in hepatic insufficiency Separate dosing from antacids by 2 h. Avoid concurrent high-fat meals Diarrhea, nausea, vomiting, hypertriglyceridemia, rash, headache, perioral paresthesias, t liver enzymes See footnote 4 for contraindicated medications. Do not administer with lopinavir/ritonavir or in severe hepatic insufficiency. Also avoid cimetidine, disulfiram, metronidazole, vitamin E, ritonavir oral solution, and alcohol when using the oral solution... 

Tipranavir PI2 Must be taken with ritonavir to achieve effective levels tipranavir 500 mg bid/ritonavir 200 mg bid. Avoid use in hepatic insufficiency. Approved for pediatric usage Take with food. Separate from ddl by at least 2 h. Avoid antacids. Avoid in patients with sulfa allergy. Refrigeration required Diarrhea, nausea, vomiting, abdominal pain, rash, t liver enzymes, hypercholesterolemia, hypertriglyceridemia See footnote 4 for contraindicated medications. Avoid concurrent fosamprenavir, saquinavir. Do not administer to patients at risk for bleeding... 

Clinically important, potentially hazardous interactions with alfuzosin, alprazolam, amphotericin B, anisindione, antacids, aprepitant, astemizole, atorvastatin, bosentan, ciclesonide, cimetidine, clorazepate, conivaptan, cyproterone, dasatinib, dexamethasone, dicumarol, didanosine, eplerenone, erythromycin, ethotoin, fentanyl, fesoterodine, fosamprenavir, fosphenytoin, grapefruit juice, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lovastatin, mephenytoin, methylprednisolone, micafungin, midazolam, nilotinib, pimozide, prednisolone, prednisone, quinidine, rifampin, rimonabant, rivaroxaban, sildenafil, silodosin, simvastatin, sirolimus, solifenacin, temsirolimus, terfenadine, tolvaptan, triazolam, vardenafil, vinblastine, vincristine, warfarin... 

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... 

Proton pump inhibitors (marked effect) and H2-receptor antagonists (modest effect) reduce atazanavir levels. Other drugs that increase gastric pH are also predicted to reduce plasma levels of atazanavir. Fosamprenavir may be similarly affected (moderate effects seen with ranitidine), although antacids and esomeprazole had little effect in one study. Omeprazole decreases indinavir levels and an antacid modestly decreased tipranavir levels. Neither ranitidine nor omeprazole had any effect on darunavir/ritonavir or lopinavir/ritonavir levels. In contrast, cimetidine, ranitidine and omeprazole have been shown to increase saquinavir levels. 

In a crossover study in healthy subjects the AUC of amprenavir (derived from a single 1.4-g dose of fosamprenavir) was decreased by 18% and the maximum plasma level by 35%, but the minimum level was not significantly altered by the concurrent use of 30 mL of an aluminium/magnesi-um hydroxide antacid (Maalox TC). ... 

Based on the limited data with other protease inhibitors, the manufacturer of amprenavir also recommends it should not be given within 1 hour of antacids. The decrease in amprenavir levels seen when fosamprenavir is given with an antacid are not considered clinically relevant, and no fosamprenavir dose adjustments are likely to be neeessary. Greater decreases were seen with ranitidine, although the minimum levels were unehanged. The UK manufaeturer states that no fosamprenavir dose adjustment is needed with ranitidine or other H2-receptor antagonists however, the US manufacturer says the combination should be used with caution because fosamprenavir may be less effective. However, no interaction occurred with esomeprazole, and this, or other proton pump inhibitors may be given at the same time as fosamprenavir. 

Ford SL, Wire MB, Lou Y, Baker KL, Stein DS. Effect of antacids and ranitidine on the single-dose pharmacokinetics of fosamprenavir. Antimicrob Agents Chemother(2005) 49,467-9. 

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