Oral midazolam-grapefruit juice drug interaction

Pediatr Dent. 2001 Jul-Aug;23(4):365-6.

Abstract

Oral midazolam is a frequently used sedative in pediatric dentistry. Although an oral form of midazolam is now commercially available, some practitioners continue to use the IV midazolam as an oral medication. If the injectible form of midazolam is administered orally, its bitter taste requires the use of a flavoring agent. Grapefruit juice is contraindicated for this purpose as it inhibits cytochrome P450 (CYP) 3A4. CYP 3A4 is located in the intestine and liver. Inhibition of this cytochrome results in delayed absorption and reduced first pass effect on midazolam. This results in increased blood plasma levels of midazolam of 56% and increased midazolam bioavailability of 35%. This can result in excessive levels of sedation for the pediatric patient. Grapefruit juice is therefore contraindicated for use with oral midazolam.

MeSH terms

  • Administration, Oral
  • Beverages / adverse effects*
  • Biological Availability
  • Child
  • Citrus / adverse effects*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors
  • Flavoring Agents / administration & dosage
  • Food-Drug Interactions*
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / adverse effects*
  • Hypnotics and Sedatives / pharmacokinetics
  • Injections, Intravenous
  • Intestinal Absorption / drug effects
  • Intestines / enzymology
  • Liver / enzymology
  • Midazolam / administration & dosage
  • Midazolam / adverse effects*
  • Midazolam / pharmacokinetics
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Taste / drug effects

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Flavoring Agents
  • Hypnotics and Sedatives
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • Midazolam