Protease inhibitors, adverse reaction

In 1995 the FDA approved saquinavir, the first protease inhibitor, for use in combination with other nucleoside analogue medications. In 1999 a soft gel capsule formulation of saquinavir with considerably improved absorption characteristics was developed. Ritonavir and indinavir have been approved for use alone or in combination with nucleoside analogue medications in people with advanced HIV disease. Nelfinavir is the first protease inhibitor labeled for use in children. Amprenavir is the newest of the protease inhibitors. Amprenavir can be taken with or without food, but it should not be taken with a high-fat meal because the fat content may decrease the absorption of the drug. The most disturbing adverse reactions to protease inhibitors consist of the lipodystrophy syndrome with severe hyperlipidemia and unpredictable fat redistributions over the body... 

Bonfanti P, Valsecchi L, Parazzini F, Carradori S, Pusterla L, Fortuna P, Timillero L, Alessi F, Ghiselli G, Gabbuti A, Di Cintio E, Martinelli C, Faggion I, Landonio S, Quirino T. Incidence of adverse reactions in HIV patients treated with protease inhibitors a cohort study. Coordinamento Italiano Studio Allergia e Infezione da HIV (CISAI) Group. J Acquir Immune Defic Syndr 2000 23(3) 236 15. 

Indinavir sulfate is a protease inhibitor and is used in combinations for the treatment of viral infection. During the high risk of HIV infection, indinavir is combined with zidovudine and lamivudine.65 Indinavir sulfate should be used with caution in patients with hepatic impairment and avoided in patients with severe liver damage. Caution is needed in diabetic patients and in patients with hemophilia. Adverse effects of indinavir sulfate include nausea, vomiting, diarrhea, fatigue, dizziness, headache, skin rashes, and allergic reactions (hematuria). 

Common adverse effects of protease inhibitors As experience with the protease inhibitors has grown, two important adverse reactions that are common to all of them have been uncovered. 

METRONIDAZOLE PROTEASE INHIBITORS t adverse effects, e.g. disulfiram-like reaction, flushing, with ritonavir (with or without lopinavir) Ritonavir and lopinavir oral solutions contain alcohol Warn patient and give alternative preparation if possible... 

PROTEASE INHIBITORS SULPHONYLUREAS t effect of tolbutamide with ritonavir Ritonavir is a potent inhibitor of CYP2C9, which metabolizes many sulphonylureas Watch for hypoglycaemia. Warn patients about hypoglycaemia - For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Reactions, Hypoglycaemia... 

The use of cisapride and its benefit to harm balance in children has been reviewed (25). Overall it is well tolerated. The most common adverse effects are diarrhea, abdominal cramps, borborygmi, and colic. Serious adverse events are rare and include isolated cases of extrapyramidal reactions, seizures in epileptic patients, cholestasis, QT interval prolongation and ventricular dysrhythmias, anorexia, and enuresis. Interactions of cisapride with other drugs are similar to those reported in adults. Co-administration of drugs that inhibit CYP3A4, such as imidazoles, macrolide antibiotics, the antidepressant nefazodone, and protease inhibitors such as ritonavir, are contraindicated. Furthermore, co-administration of anticholinergic drugs can compromise the beneficial effects of cisapride. 

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