Drug Interactions between cannabis and guaifenesin / oxtriphylline

MONITOR: Concomitant use of cannabis (marijuana) may decrease the plasma concentrations of theophylline. Smoking marijuana has been reported to increase theophylline clearance, with effect similar to that of smoking tobacco. The mechanism of interaction has not been established, but may involve induction of CYP450 1A2-mediated metabolism by the cannabinoids in marijuana. In one study, theophylline clearance was increased by an average of 42% in chronic smokers of either marijuana or tobacco administered single oral doses of theophylline compared to nonsmokers of either substance. There was an additive increase in total clearance of approximately 79% in subjects who smoked both marijuana and tobacco compared to nonsmokers. It is not known whether, and to what extent, the interaction may occur with other routes of administration of cannabis or any of its cannabinoids. In vitro data suggest that delta-9-tetrahydrocannabinol may induce CYP450 1A2, while cannabidiol may induce or inhibit CYP450 1A2 at clinically relevant concentrations.

MANAGEMENT: Theophylline levels should be monitored closely in patients who use marijuana or its cannabinoids. Dosage adjustments may be required following initiation, discontinuation, or change of cannabis/cannabinoid use.