300 Midazolam
and rat experiments find that midazolam makes alcohol more appealing. The
HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syn-
drome) drug saquinavir and the antibiotic erythromycin increase midazolam
levels in the body and make effects last longer. The antacid and ulcer medi-
cation cimetidine (such as Tagamet) can lengthen sedation from a midazolam
dose. Some research indicates that drinking grapefruit juice increases mida-
zolam’s ability to act upon a person, but other research does not support that
finding. The tuberculosis medicine rifampin and the epilepsy drugs phenytoin
and carbamazepine diminish midazolam’s effectiveness.
Cancer.Rat and mice experiments have produced no cancer even when
midazolam was given daily for two years at 25 times the recommended hu-
man dose. The same usage of the drug at about 225 times the recommended
human dose, however, produced liver and thyroid tumors. Relevance of the
latter outcome to human medical use, involving normal dosage and typically
using the drug for one day, is unclear. Gene mutations are considered an
element in causing cancer, and midazolam did not produce mutations in as-
sorted standard tests, nor were they observed in a study of patients receiving
the drug.
Pregnancy.The drug has been given to mice, rats, and rabbits at 5 to 32
times the normal human dose without producing birth defects. Researchers
conducting one experiment concluded, however, that the drug altered behav-
ior of mice after fetal exposure (making males more uneasy and females less
uneasy) while slowing their development. Tests indicate that the drug will
pass from a pregnant woman into the fetus. The substance has been success-
fully used to treat eclampsia, a serious disease of late pregnancy involving
convulsions, but midazolam is generally not desirable for pregnant women.
The drug passes into the milk supply of nursing mothers, and caution is rec-
ommended about breast-feeding in such circumstances.
Additional scientific information may be found in:Curran, H.V., and B. Birch. “Differentiating the Sedative, Psychomotor and Amnesic
Effects of Benzodiazepines: A Study with Midazolam and the Benzodiazepine
Antagonist, Flumazenil.”Psychopharmacology103 (1991): 519–23.
Dundee, J.W. “Fantasies during Sedation with Intravenous Midazolam or Diazepam.”
Medico-Legal Journal58 (1990, pt. 1): 29–34.
Gupta, A., et al. “The Effects of Midazolam and Flumazenil on Psychomotor Function.”
Journal of Clinical Anesthesia9 (1997): 21–25.
Kelly, D.J., et al. “The Effects of Midazolam on Pure Tone Audiometry, Speech Audi-
ometry, and Audiological Reaction Times in Human Volunteers.”Anesthesia and
Analgesia88 (1999):1064–68.
Langlois, S., et al. “Midazolam: Kinetics and Effects on Memory, Sensorium, and He-
modynamics.”British Journal of Clinical Pharmacology23 (1987): 273–78.
“Midazolam.”Medical Letter on Drugs and Therapeutics28 (1986): 73–74.
Nordt, S.P., and R.F. Clark. “Midazolam: A Review of Therapeutic Uses and Toxicity.”
Journal of Emergency Medicine15 (1997): 357–65.