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

MONITOR: Coadministration with alcohol or other central nervous system (CNS) depressants may enhance the sedative effects of allopurinol and increase the likelihood and/or severity of central nervous system (CNS) side effects, such as drowsiness, somnolence, vertigo, and ataxia.

MANAGEMENT: Caution for increased CNS adverse effects is advised if allopurinol is coadministered with alcohol, other CNS depressants, or agents that cause dizziness or vertigo. Patients should not drive, operate machinery, or engage in hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them.

MONITOR: Allopurinol may inhibit the metabolism of xanthines (e.g., theophylline), possibly increasing serum concentrations and the risk of toxicity. When theophylline was coadministered with allopurinol, a 25% increase in steady-state theophylline serum concentrations were observed. This interaction may be more likely to occur with daily allopurinol doses of 600 mg or more. The mechanism may related to allopurinol's inhibition of xanthine oxidase, an enzyme involved in the metabolism of theophylline.

MANAGEMENT: Closer clinical and laboratory monitoring for adverse effects is advised if theophylline is used concomitantly with allopurinol. Additionally, theophylline levels should be more closely monitored following the initiation or discontinuation of allopurinol treatment, and the theophylline dosage adjusted as necessary in accordance with the prescribing information. Patients should be advised to report any signs of theophylline toxicity to their doctor (e.g., nausea, vomiting, diarrhea, headache, restlessness, insomnia, or irregular heartbeat).

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.

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.