Drug Interaction Report

MONITOR: The coadministration of delavirdine in combination with other non-nucleoside reverse transcriptase inhibitors (NNRTIs) like efavirenz or nevirapine has not been studied. However, since all three drugs are metabolized by the CYP450 3A4 isoenzyme, pharmacokinetic interactions may theoretically occur. Delavirdine is a potent inhibitor of CYP450 3A4 and may increase the plasma concentrations of both efavirenz and nevirapine. Nevirapine, on the other hand, is an inducer of the isoenzyme and may decrease the plasma concentrations of delavirdine. Efavirenz may have variable effects on delavirdine because it can induce as well as competitively inhibit CYP450 3A4 metabolism.

MANAGEMENT: Clinical monitoring for altered effects of both delavirdine and the other NNRTI may be appropriate following addition or withdrawal of one or the other drug.

ADJUST DOSING INTERVAL: Administration with food increases the plasma concentrations of efavirenz and may increase the frequency of adverse reactions. According to the product labeling, administration of efavirenz capsules (600 mg single dose) with a high-fat/high-caloric meal (894 kcal, 54 g fat, 54% calories from fat) or a reduced-fat/normal-caloric meal (440 kcal, 2 g fat, 4% calories from fat) was associated with mean increases of 39% and 51% in efavirenz peak plasma concentration (Cmax) and 22% and 17% in systemic exposure (AUC), respectively, compared to administration under fasted conditions. For efavirenz tablets, administration of a single 600 mg dose with a high-fat/high-caloric meal (approximately 1000 kcal, 500-600 kcal from fat) resulted in a 79% increase in mean Cmax and a 28% increase in mean AUC of efavirenz relative to administration under fasted conditions.

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of efavirenz. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Efavirenz should be taken on an empty stomach, preferably at bedtime. Dosing at bedtime may improve the tolerability of nervous system symptoms such as dizziness, insomnia, impaired concentration, somnolence, abnormal dreams and hallucinations, although they often resolve on their own after the first 2 to 4 weeks of therapy . Patients should be advised of the potential for additive central nervous system effects when efavirenz is used concomitantly with alcohol or psychoactive drugs, and to avoid driving or operating hazardous machinery until they know how the medication affects them.

The recommended maximum number of medicines in the 'NNRTIs' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'NNRTIs' category:

• efavirenz
• Rescriptor (delavirdine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.