Saquinavir with itraconazole

The information about the interactions of protease inhibitors with itraconazole is limited. On the basis of the available data, it is possible that itraconazole has greater effects than ketoconazole , (below), on protease inhibitor levels. The manufacturers of indinavir advise modestly reducing the indinavir dose to 600 mg every 8 hours if it is to be given with itraconazole. The UK manufacturer of saquinavir recommends monitoring for saquinavir toxicity if itraconazole is used. Some protease inhibitors, especially ritonavir and possibly indinavir, may increase itraconazole levels and most manufacturers say that doses of itraconazole greater than 200 mg a day are not recommended. The US manufacturers of amprenavir recommend increased monitoring for adverse effects and state that the dose of itraconazole may need to be reduced if it is greater than 400 mg daily. ... 

Sildenafil doses should be decreased when any potent cytochrome P450 3A4 inhibitor is used (e g., cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and saquinavir). Vardenafil doses vary accordingto which agent is used (2.5 mg q 72 h for ritonavir, 2.5 mg q 24 h for indinavir, ketoconazole 400 mg daily, and itraconazole 400 mg daily and 5 mg q 24 h for ketoconazole 200 mg daily, itraconazole200 mg daily, and erythromycin). Tadalafil doses are reduced only when it is used with the most potent cytochrome P450 3A4 inhibitors (e g., ketoconazole or ritonavir). 

MODAFINIL 1. ANTIBIOTICS-clarithromycin, telithromycin 2. ANTIFUNGALS-itraconazole, ketoconazole 3. ANTIVIRALS-indinavir, nelfinavir, ritonavir, saquinavir t plasma concentrations of modafinil, with risk of adverse effects Due to inhibition of CYP3A4, which has a partial role in the metabolism of modafinil Be aware. Warn patients to report dose-related adverse effects, e.g. headache, anxiety... 

ITRACONAZOLE, KETOCONAZOLE PROTEASE INHIBITORS Possibly t levels of ketoconazole by amprenavir, indinavir and ritonavir (with or without lopinavir). Conversely, indinavir, ritonavir and saquinavir levels t by itraconazole and ketoconazole Inhibition of, or competition for, CYP3A4-mediated metabolism Use itraconazole with caution and monitor for adverse effects. No dose adjustment is recommended for doses <400 mg/day of ketoconazole... 

The HIV protease inhibitor saquinavir has hmited and variable oral systemic availability and ritonavir, an inhibitor of CYP450 and P glycoprotein, is widely used to increase its systemic exposure. A small pilot study in three HIV-infected patients has suggested that oral itraconazole can have similar effects on the oral availability of saquinavir (109). Concomitant use of itraconazole 200 mg/day with a combination of saquinavir and two nucleoside reverse transcriptase inhibitors led to a 2.5-to 6.9-fold increase in the AUC of saquinavir, a 2.0- to 5.4-fold increase in peak plasma concentrations, and a 1.6-to 17-fold increase in trough plasma concentrations. The effect of itraconazole on saquinavir was comparable to that of ritonavir. 

Hoetelmans RM. Itraconazole as an alternative for ritonavir liquid formulation when combined with saquinavir. AIDS 2000 14(l) 89-90. 

Clinically important, potentially hazardous interactions with alcohol, aprepitant, clarithromycin, CNS depressants, delavirdine, digoxin, efavirenz, fluconazole, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ivermectin, kava, ketoconazole, propoxyphene, ritonavir, saquinavir, St John s wort... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, bedomethasone, buprenorphine, calcium, chloramphenicol, cimetidine, dobazam, clorazepate, cyclosporine, cyproterone, darunavir, dasatinib, delavirdine, dexamethasone, diazoxide, disulfiram, dopamine, fesoterodine, fluconazole, flunisolide, fluoxetine, fosamprenavir, ginkgo biloba, hydrocortisone, imatinib, indinavir, influenza vaccines, isoniazid, isradipine, itraconazole, lacosamide, lapatinib, lopinavir, meperidine, methylprednisolone, midazolam, mivacurium, nelfinavir, nilotinib, nilutamide, phenylbutazone, piracetam, posaconazole, prednisolone, prednisone, primrose, ritonavir, rivaroxaban, sage, saquinavir, solifenacin, St John s wort, sucralfate, telithromycin, temsirolimus, teniposide, ticlopidine, tizanidine, tolvaptan, triamcinolone, uracil/tegafur, vigabatrin... 

Clinically important, potentially hazardous interactions with amphetamines, aprepitant, astemizole, atazanavir, azithromycin, azole antifungals, clarithromycin, darunavir, dirithromycin, erythromycin, fluoxetine, fosamprenavir, grapefruit juice, imatinib, indinavir, itraconazole, ketoconazole, methylphenidate, nefazodone, nelfinavir, nilotinib, pemoline, phenothiazines, protease inhibitors, quinidine, ritonavir, saquinavir, sertraline, sparfloxacin, sulpiride, telithromycin, thioridazine, tipranavir, tricyclic antidepressants, troleandomycin, voriconazole, zileuton, ziprasidone... 

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... 

Clinically important, potentially hazardous interactions with amprenavir, amyl nitrite, atazanavir, delavirdine, erythromycin, fosamprenavir, indinavir, isosorbide dinitrate, isosorbide mononitrate, itraconazole, ketoconazole, nelfinavir, nitrates, nitroglycerin, ritonavir, saquinavir... 

The AUC of erlotinib has been found to be increased by 66% when given with ketoconazole 200 mg twice daily for 5 days. The manufacturers advise caution with concurrent use, and recommend that the dose of erlotinib should be reduced if severe adverse reactions occur when given with strong CYP3A4 inhibitors. They specifically name atazanavir, clarithromycin, erythromycin, grapefruit and grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, neltinavir, ritonavir, saquinavir, telithromycin, troleandomycin and voriconazole. ... 

Koks CHW, Van Heeswijk RPG, Veldkamp AI, Meenhorst PL, Mulder J-W, van der Meer JTM, Beijnen JH, Hoetelmans RMW. Itraconazole as an alternative for ritonavir liquid formulation when combined with saquinavir. AIDS (2000) 14, 89-90. 

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