Drugs to Avoid/Use with Caution with Protease Inhibitors

• Non-sedating antihistamines

• Long-acting opiate analgesics

• Long-acting benzodiazepines

• Promotility agents

• Antiarrhythmics

• Calcium channel blockers

• Anticonvulsants

• Ergotamines and dihydroergotamine

• Illicit drugs

• Coumarin anticoagulants

• Oral contraceptives

• Lipid lowering agents (statins)

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• The non-sedating antihistamines astemizole (Hismanal) and terfenadine (Seldane) are substrates of CYP3A4. In the presence of CYP3A4 inhibitors, concentrations of these agents are significantly increased, and the risk of dose-related adverse events (including cardiotoxicity) is increased. Similar concern exists for cisapride. Therefore, use of these agents should be avoided in people currently taking medications that inhibit CYP450

• The metabolism of many benzodiazepines may be signficantly reduced by the presence of CYP450 inhibitors. In order to minimize the risk of excessive sedation, practitioners may wish to consider reducing the benzodiazepine dose, or using an agent with a different metabolic pathway (e.g., lorazepam, oxazepam, or temazepam)

• Calcium channel blockers are primarily metabolized by CYP3A. Therefore, these agents should be used cautiously with inhibiting agents, in order to avoid excessive drops in blood pressure.

• Many antidepressants are substrates of CYP2D6. They are at risk of interacting with agents that inhibit this isoenzyme; greatest precaution with ritonavir.

• Oral contraceptives are glucuronidated. Significant reductions in ethinyl estradiol concentrations are seen in the presence of ritonavir or nelfinavir. Patients taking these agents should be counselled about using an alternative method of birth control, such as barrier contraception