Savvy Psychopharmacology

Grapefruit juice and psychotropics: How to avoid potential interactions

Current Psychiatry. 2015 June;14(6):60-66

References

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Carbamazepine product labeling lists grapefruit juice as a CYP3A4 inhibitor that is expected to or has been found to increase plasma levels of the drug.²⁰ Carbamazepine’s bioavailability is influenced by intestinal CYP3A4 activity; in a randomized, 2-phase crossover study of 10 patients with epilepsy, grapefruit juice was found to increase AUC of carbamazepine by 41% and Cmax by 40%.^23,36

Lurasidone and pimozide, although not specifically studied, have product labels that recommend avoiding grapefruit juice because it could inhibit metabolism of these agents by CYP3A4.²⁰ Of particular concern is the potential for elevated levels of pimozide to increase the risk of adverse cardiovascular effects including QT interval prolongation.¹⁹

Midazolam. Although grapefruit juice does not affect the disposition of IV midazolam, pretreatment with grapefruit juice was found to increase the AUC and Cmax of oral midazolam by 52% and 56%, respectively.³⁰

Other considerations in drug-grapefruit interactions
Cautionary statements about a possible interaction with grapefruit juice for many other psychotropics can be found in commonly used drug information references or online sources. If you are concerned about a possible interaction and avoiding grapefruit products is not feasible, consider a different medication in the same class.

However, you also should consider the level of evidence supporting any purported interaction. Several psychotropic agents do have studies or case reports supporting an interaction with grapefruit, but cautionary statements could be based on theoretical concerns because of a medication’s bioavailability, metabolic pathway, and concern for increased adverse events related to higher drug concentrations. Adding to the confusion, cautionary statements can be found about medications, such as clozapine, that have not been shown to have an interaction with grapefruit juice when studied.

With many of the drugs that have a reported or theoretical interaction with grapefruit, data are inconsistent as to whether the resulting interaction will be clinically relevant. A number of variables relating to the individual patient, grapefruit product, or particular drug can play a role in the significance of an interaction. Additionally, effects on drug disposition can last for a few days after consuming a grapefruit product.

Keep alert to situations of increased risk
Recall that the case patient, Ms. H, presented with an elevated carbamazepine level and suffered resulting adverse effects because of an interaction between the drug and grapefruit juice. Although Ms. H was careful to separate intake of grapefruit juice from carbamazepine administration, grapefruit’s inhibition of intestinal CYP3A4 still was present, leading to the interaction.

It is important for health care professionals to recognize this potential risk and to advise patients regarding possible interactions between medications and grapefruit products.

Related Resources
• U.S. Food and Drug Administration. Grapefruit juice and medicine may not mix. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm292276.htm.
• Hanley MJ, Cancalon P, Widmer WW, et al. The effect of grapefruit juice on drug disposition. Expert Opin Drug Metab Toxicol. 2011;7(3):267-286.
• Andrade C. Fruit juice, organic anion transporting polypeptides, and drug interactions in psychiatry. J Clin Psychiatry. 2014;75(11):e1323-e1325.

Drug Brand Names
Alprazolam • Xanax Lurasidone • Latuda
Buspirone • BuSpar Midazolam • Versed
Carbamazepine • Tegretol Methadone • Dolophine
Clomipramine • Anafranil Nefazodone • Serzone
Clozapine • Clozaril Olanzapine • Zyprexa
Diazepam • Valium Pimozide • Orap
Felodipine • Plendil Quetiapine • Seroquel
Fexofenadine • Allegra Sertraline • Zoloft
Fluoxetine • Prozac Trazodone • Desyrel
Fluvoxamine • Luvox Triazolam • Halcion
Haloperidol • Haldol Ziprasidone • Geodon
Levothyroxine • Levoxyl, Synthroid

Disclosure
The author reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

References

PSYCHIATRY UPDATE 2015

Grapefruit juice and psychotropics: How to avoid potential interactions

References

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