Drug Interactions: Inhibitors of CYP3A4 Isozymes: Caution is advised when
midazolam is administered concomitantly with drugs that are known to inhibit the cytochrome P450 3A4 enzyme system
(ie, some drugs in the drug classes of azole antimycotics, protease inhibitors, calcium channel antagonists, and
macrolide antibiotics). Drugs such as erythromycin, diltiazem, verapamil, ketoconazole, fluconazole and itraconazole
were shown to significantly increase the C max and AUC of orally administered midazolam. These drug
interactions may result in increased and prolonged sedation due to a decrease in plasma clearance of midazolam.
Although not studied, the potent cytochrome P450 3A4 inhibitors ritonavir and nelfinavir may cause intense and
prolonged sedation and respiratory depression due to a decrease in plasma clearance of midazolam. Caution is advised
when VERSED Syrup is used concomitantly with these drugs. Dose adjustments should be considered and possible
prolongation and intensity of effect should be anticipated.
Inducers of CYP3A4 Isozymes: Cytochrome P450 inducers, such as rifampin, carbamazepine, and
phenytoin, induce metabolism and caused a markedly decreased C max and AUC of oral midazolam in adult
studies. Although clinical studies have not been performed, phenobarbital is expected to have the same effect.
Caution is advised when administering VERSED Syrup to patients receiving these medications and if necessary dose
adjustments should be considered.
CNS Depressants: One case was reported of inadequate sedation with chloral hydrate and later
with oral midazolam due to a possible interaction with methylphenidate administered chronically in a 2-year-old boy
with a history of Williams syndrome. The difficulty in achieving adequate sedation may have been the result of
decreased absorption of the sedatives due to both the gastrointestinal effects and stimulant effects of
The sedative effect of VERSED Syrup is accentuated by any concomitantly administered medication which depresses
the central nervous system, particularly narcotics (eg, morphine, meperidine and fentanyl), propofol, ketamine,
nitrous oxide, secobarbital and droperidol. Consequently, the dose of VERSED Syrup should be adjusted according to
the type and amount of concomitant medications administered and the desired clinical response.
No significant adverse interactions with common premedications (such as atropine, scopolamine, glycopyrrolate,
diazepam, hydroxyzine, and other muscle relaxants) or local anesthetics have been observed.