Drug Interactions between guaifenesin / oxtriphylline and terbinafine

MONITOR: The coadministration of terbinafine and theophylline may result in elevated plasma concentrations of the latter. In a randomized, crossover study consisting of 12 healthy volunteers, terbinafine (250 mg orally once a day for 4 days) increased the area under the serum concentration-time curve (AUC) and half-life of a single dose of theophylline (5 mg/kg) by 16% and 24%, respectively, compared to placebo. Oral clearance decreased by 14%. The exact mechanism is unknown but may involve inhibition of the CYP450 1A2 enzymatic pathway, which is responsible for the metabolism of theophylline and other methylxanthines such as caffeine, the clearance of which has also been found to be reduced (21%) by terbinafine.

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should be monitored closely during concomitant therapy with terbinafine. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever terbinafine is added to or withdrawn from therapy. Due to the long elimination half-life of terbinafine, especially following prolonged use, potential drug interactions may be observed for several months after discontinuation of terbinafine therapy. Patients should be advised to report any signs of theophylline toxicity including nausea, vomiting, diarrhea, headache, restlessness, insomnia, or irregular heartbeat to their physicians.