Drug Interactions between aminophylline / ephedrine / guaifenesin / phenobarbital and oxcarbazepine

MONITOR: Barbiturates may decrease serum levels and therapeutic effects of the methylxanthines. The mechanism is barbiturate induction of CYP450 3A4 and 1A2 hepatic metabolism of methylxanthines.

MANAGEMENT: Close observation for clinical and laboratory evidence of decreased methylxanthine effect is indicated if these drugs must be used together. Patients should be advised to notify their physician if they experience a worsening of their respiratory symptoms.

MONITOR: Coadministration with potent CYP450 inducers may decrease the plasma concentrations of the pharmacologically active 10-monohydroxy metabolite of oxcarbazepine known as MHD. Administration of oxcarbazepine 900 mg/day in combination with carbamazepine 400 to 2000 mg/day has resulted in an average reduction of MHD plasma concentrations by approximately 40%. Phenytoin 250 to 500 mg/day and phenobarbital 100 to 150 mg/day have reduced the plasma concentrations of MHD on average by approximately 30% and 25%, respectively, when oxcarbazepine was coadministered at 600 to 1800 mg/day. Since MHD is responsible for much of the pharmacologic effects of oxcarbazepine, the potential for altered anticonvulsant activity should be considered. Oxcarbazepine had no significant effect on the pharmacokinetics of carbamazepine and phenobarbital, but increased the plasma concentrations of phenytoin by 40% when administered at dosages greater than 1200 mg/day.

MANAGEMENT: The possibility of diminished therapeutic effects of oxcarbazepine should be considered when used in combination with potent CYP450 inducers such as carbamazepine, phenobarbital, phenytoin, primidone (which is metabolized to phenobarbital), rifampin, and St. John's wort. Close clinical and laboratory monitoring is recommended whenever a CYP450 inducer is added to or withdrawn from oxcarbazepine therapy, and the dosage adjusted as necessary.

Ephedrine-methylxanthine combinations are used for the treatment of asthma but the efficacy of the combination has been questioned. This combination may lead to increased xanthine side effects. The mechanism is unknown, but may be related to synergistic pharmacologic effects. Patients using this combination should be closely monitored for side effects such as nausea, vomiting, tachycardia, nervousness, or insomnia. If side effects are noted, the dosage of the xanthine may need to be decreased.