Oral midazolam-grapefruit juice drug interaction.

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.