Antiviral Protease Inhibitors

Because of reported antiplatelet effects, patients using anticlotting medications (eg, warfarin, aspirin, ibuprofen) should use garlic cautiously. Additional monitoring of blood pressure and signs and symptoms of bleeding is warranted. Garlic may reduce the bioavailability of saquinavir, an antiviral protease inhibitor, but it does not appear to affect the bioavailability of ritonavir. 

The first-developed method for the enantioselective construction of secondary aminated stereocenters, by Knowles, was the hydrogenation of enamides such as II. In the context of a synthesis of BILN 2061 15, an antiviral protease inhibitor, Anne-Marie Faucher of Boehringer-Ingeiheim, Laval has shown (Organic Lett. 2004, 6, 2901) that such hydrogenations can be effected even in the presence of a terminal vinyl group. The product 12 was carried on to 15 over several steps, including the Ru (Hoyveda) cyclization of 13 to 14. 

FLECAINIDE ANTIVIRALS - PROTEASE INHIBITORS Amprenavir, ritonavir and possibly saquinavir and tipranavir with ritonavir t flecainide levels, with risk of ventricular arrhythmias Uncertain possibly inhibition of CYP3A4- and CYP2D6-mediated metabolism of flecainide Manufacturers recommend avoiding co-administration of flecainide with amprenavir, ritonavir and saquinavir... 

CALCIUM CHANNEL BLOCKERS ANTIVIRALS-PROTEASE INHIBITORS Plasma concentrations of calcium channel blockers are t by protease inhibitors Protease inhibitors inhibit CYP3A4-mediated metabolism of calcium channel blockers. Also, ritonavir inhibits CYP2C9-mediated metabolism of verapamil, and ritonavir and saquinavir both inhibit intestinal P-gp, which may T the bioavailability of verapamil Monitor PR, BP and ECG closely 1 dose of calcium channel blocker if necessary (e.g. the manufacturers of diltiazem suggest starting at 50% of the standard dose and titrating to effect)... 

POTASSIUM-SPARING DIURETICS ANTIVIRALS-PROTEASE INHIBITORS Possibly t adverse effects of eplerenone with nelfinavir, ritonavir (with or without lopinavir) and saquinavir Inhibition of CYP3A4-mediated metabolism of eplerenone Avoid concomitant use... 

IVABRADINE ANTIVIRALS-PROTEASE INHIBITORS t levels with nelfinavir and ritonavir Uncertain Avoid co-administration... 

CILOSTAZOL ANTIVIRALS-PROTEASE INHIBITORS Amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir t cilostazol levels These protease inhibitors inhibit CYP3A4-mediated metabolism of cilostazol Avoid co-administration... 

SYMPATHOMIMETICS ANTIVIRALS-PROTEASE INHIBITORS 1. Risk of serotonin syndrome when dexamfetamine is administered with ritonavir 2. Indinavir may t phenylpropanolamine levels 1. Protease inhibitors inhibit CYP2D6-mediated metabolism 2. Likely inhibition of phenylpropanolamine metabolism 1. Avoid co-administration 2. Monitor BP closely watch for marked t BP... 

ST JOHN S WORT ANTIVIRALS-PROTEASE INHIBITORS Markedly l levels and efficacy of protease inhibitors by St John s wort Possibly t CYP3A4-mediated metabolism of the protease inhibitors Avoid co-administration... 

BUSPIRONE ANTIVIRALS-PROTEASE INHIBITORS T adverse effects, e.g. prolonged sedation Inhibition of CYP3A4-mediated metabolism of BZDs and buspirone Watch closely for T sedation 1 dose of sedative as necessary. Some recommend considering substituting long-acting for shorter-acting BZDs with less active metabolites (e.g. lorazepam for diazepam)... 

DISULFIRAM ANTIVIRALS-PROTEASE INHIBITORS t risk of disulfiram reaction with ritonavir (with or without lopinavir) Ritonavir and lopinavir/ritonavir oral solutions contain 43% alcohol Warn patients. Consider using capsule preparations as an alternative... 

DOCETAXEL ANTIVIRALS-PROTEASE INHIBITORS t risk of adverse effects of docetaxel Inhibition of CYP3A4-mediated metabolism. Also inhibition of P-gp efflux of vinblastine Use with caution. Additional monitoring required. Monitor FBC weekly... 

SULPHONYLUREAS ANTIVIRALS-PROTEASE INHIBITORS t adverse effects of tolbutamide with ritonavir (e.g. myelosuppression, peripheral neuropathy, mucositis) Uncertain Monitor blood sugar closely... 

THYROID HORMONES ANTIVIRALS - PROTEASE INHIBITORS 1 efficacy of levothyroxine by ritonavir (with or without lopinavir) and possibly indinavir and nelfinavir Uncertain possibly T metabolism via induction of glucuronosyl transferases Monitor thyroid function closely... 

ANAESTHETICS - LOCAL ANTIVIRALS-PROTEASE INHIBITORS t adverse effects of lidocaine with lopinavir and ritonavir Uncertain t bioavailability Caution consider using an alternative local anaesthetic... 

LOPERAMIDE ANTIVIRALS - PROTEASE INHIBITORS t risk of adverse effects when loperamide is co-ingested with ritonavir Ritonavir inhibits P-gp and CYP3A4 Monitor for clinical effect consider 1 dose if necessary. Stop if there are signs of abdominal distension in patients with HIV as toxic megacolon has been reported... 

PROTON PUMP INHIBITORS ANTIVIRALS - PROTEASE INHIBITORS ... 

NORETHISTERONE ANTIVIRALS - PROTEASE INHIBITORS t adverse effects with amprenavir and atazanavir Uncertain Watch for early features of toxicity of amprenavir and atazanavir, and adjust the dose accordingly... 

PHOSPHODIESTERASE TYPE 5 INHIBITORS ANTIVIRALS-PROTEASE INHIBITORS t sildenafil, tadalafil and vardenafil levels Inhibition of CYP3A4- and possibly CYP2C9-mediated metabolism of sildenafil Use with caution monitor BP closely. UK manufacturers recommend avoiding co-administration of vardenafil with protease inhibitors in people >75 years. US manufacturers recommend using with caution, starting with a daily dose of 2.5 mg... 

CANNABIS ANTIVIRALS-PROTEASE INHIBITORS-indinavir, nelfinavir, nevirapine, ritonavir, saquinavir Cannabis may cause l plasma concentrations of protease inhibitors, particularly indinavir and nelfinavir Cannabis may cause inhibition or induction of CYP3A4 isoenzymes, which metabolize these protease inhibitors Be aware. Regular monitoring of viral indicators is necessary... 

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