Amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir

Adverse effects. A variety of effects has been associated with these agents, including gastrointestinal disturbance, headache, dizziness, sleep disturbance, raised liver enzymes, neutropenia, pancreatitis, and rashes.

Interactions. Involvement of protease inhibitors with the cytochrome P450 system provides scope for interaction with numerous substances. Agents that induce P450 enzymes (e.g. rifampicin, St John's wort) accelerate their metabolism, and reduce plasma concentration; enzyme inhibitors (e.g. ketoconazole, cimetidine) raise their plasma concentration; competition with other drugs for the cytochrome enzymes can lead to variable results. Ritonavir is itself a powerful inhibitor of CYP 3A4 and CYP 2D6. This effect is utilised when ritonavir in small quantity is combined (in capsules) with lopinavir to inhibit its metabolism and increase its therapeutic efficacy. The present account should be sufficient to warn the physician, and thereby the patient, to take particular heed when seeking to co-administer any drug a with protease inhibitor.

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