Possible Interaction: Caffeine and Midazolam

“Results: CAF caused a statistically significant increase in AC3 positive cells when coadministered with midazolam (p = 0.002), ketamine (p = 0.014), or fentanyl (p < 0.001).”

“Such alterations in hepatic P450 significantly resulted in an increase in the plasma concentrations of substrate drugs caffeine [1A2], tolbutamide [2C11], chlorzoxazone [2E1], and midazolam [3A2]) for each P450 isoform, and thus, the hypnotic action of midazolam could be significantly prolonged.”

“The synergistic production of fine motor dyskinesia by the concurrent administration of caffeine and midazolam may be relevant to the triggering of anxiety attacks by caffeine observed in panic disorder patients.”

“The conspicuous synergistic action of caffeine on the motor control deficit produced by midazolam contrasts with the typical antagonism found between the benzodiazepines and methylxanthines when performance is evaluated by psychomotor tests not requiring fine motor control.”

“When each dose of caffeine was combined with 3 mg/kg midazolam , a marked synergism in motor performance impairment occurred.”

“Mixtures of low doses of caffeine and midazolam frequently antagonized GABA responses.”

“It was however possible to detect a narrow range of concentrations of midazolam which had an additive effect to the enhancement by caffeine.”

“The hypodipsic effect of caffeine was reversed by benzodiazepine treatment ( midazolam or diazepam).”