Drug Interaction Report

MONITOR: Limited data suggest that midodrine may potentiate the risk of akathisia associated with promethazine. The mechanism is unknown but may involve competitive inhibition of CYP450 2D6 metabolism. In nine healthy volunteers, six experienced akathisia after receiving a single 10 mg oral dose of midodrine followed 60 minutes later by a 25 mg intravenous dose of promethazine, compared to four after receiving promethazine and placebo. No subject experienced akathisia following midodrine alone. The severity of akathisia was also significantly greater with the combination than with promethazine alone.

MANAGEMENT: Patients treated with midodrine and promethazine in combination should be monitored for signs and symptoms of akathisia such as tension, restlessness, insomnia, and anxiety. One or both drugs may need to be discontinued if akathisia occurs.

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.