Drug Interaction Report

MONITOR: The coadministration with interferons has been associated with decreases in clearance and increases in plasma concentration and elimination half-life of theophylline. The mechanism is unknown but may be related to interferon-induced suppression of hepatic CYP450 enzymes, particularly, CYP450 1A2. Physiologic events and drugs that induce interferon synthesis (e.g., viral infection, influenza vaccination) have also been reported to decrease metabolism and potentiate the effects of certain drugs including theophylline. Some authorities suggest that the interaction with peginterferon alfa-2a may be maximal after more than 4 weeks of concomitant therapy.

MANAGEMENT: Caution is advised if theophylline or other methylxanthines are administered with an interferon. Pharmacologic response and serum theophylline levels should be monitored and the dosage adjusted accordingly, particularly following initiation or discontinuation of interferon therapy in patients who are stabilized on their methylxanthine regimen. Patients should be advised to contact their physician if they experience signs and symptoms of theophylline toxicity such as nausea, vomiting, diarrhea, headache, restlessness, insomnia, or irregular heartbeat.

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of ribavirin. Administration of a single oral dose of ribavirin following a high-fat meal delayed absorption (Tmax was doubled) but increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by up to 70% compared to administration in the fasting state.

MANAGEMENT: To ensure maximal oral absorption, ribavirin should be administered with or immediately after a meal.