Drug Interaction Report

MONITOR CLOSELY: Certain drugs such as carbonic anhydrase inhibitors and drugs with anticholinergic activity (e.g., antihistamines, antispasmodics, neuroleptics, phenothiazines, skeletal muscle relaxants, tricyclic antidepressants, disopyramide) may potentiate the risk of oligohidrosis and hyperthermia associated occasionally with the use of topiramate, particularly in pediatric patients. These agents may alter electrolyte and fluid balance (carbonic anhydrase inhibition), inhibit peripheral sweating mechanisms (anticholinergic effect), and/or interfere with core body temperature regulation in the hypothalamus (neuroleptics and phenothiazines), resulting in the inability to adjust to temperature changes, especially in hot weather. Also, agents with anticholinergic activity frequently cause drowsiness and other central nervous system-depressant effects, which may be additively or synergistically increased in patients also treated with topiramate.

MANAGEMENT: Caution is advised when topiramate is prescribed with other drugs that predispose patients to heat-related disorders, including carbonic anhydrase inhibitors and drugs with anticholinergic activity. Patients, particularly pediatric patients, should be monitored closely for evidence of decreased sweating and increased body temperature, especially in warm or hot weather. Proper hydration before and during vigorous activities or exposure to warm temperatures is recommended. Patients (or their guardians or caregivers) should contact their physician immediately if they are not sweating as usual, with or without a fever. Ambulatory patients treated with topiramate and agents with anticholinergic activity should also be made aware of the possibility of additive CNS effects (e.g., drowsiness, dizziness, lightheadedness, confusion) and counseled to avoid activities requiring mental alertness until they know how these agents affect them.

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.