Grapefruit - Anafranil (Clomipramine) Interaction

Interaction Details

Clomipramine is classified as belonging to the following category: Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C19.
In vitro research suggests that grapefruit juice might inhibit CYP2C19 enzymes. Also, a small clinical study shows that taking grapefruit juice with clopidogrel, an antiplatelet prodrug that is metabolized primarily by CYP2C19, decreases plasma levels of the active metabolite and impairs the antiplatelet effect of clopidogrel. This effect is likely due to grapefruit-induced inhibition of CYP2C19.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1
• Holmberg MT, Tornio A, Neuvonen M, Neuvonen PJ, Backman JT, Niemi M. Grapefruit juice inhibits the metabolic activation of clopidogrel. Clin Pharmacol Ther. 2014 Mar;95(3):307-13.

Interaction Details

Clomipramine is classified as belonging to the following category: Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP1A2.
In vitro research suggests that grapefruit juice might inhibit CYP1A2 enzymes. So far, this interaction has not been reported in humans.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1

Interaction Details

Clomipramine is classified as belonging to the following category: Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C9.
In vitro research suggests that grapefruit juice might inhibit CYP2C9 enzymes. So far, this interaction has not been reported in humans.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1

Interaction Details

Clomipramine is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates

Grapefruit juice can increase levels of drugs metabolized by CYP3A4.
Clinical research shows that grapefruit juice can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. When taken orally, effects of grapefruit juice on CYP3A4 levels appear to last at least 48 hours.
Professional consensus recommends the consideration of patient age, existing medical conditions, additional medications, and the potential for additive adverse effects when evaluating the risks of concomitant use of grapefruit juice with any medication metabolized by CYP3A4. While all patients are at risk for interactions with grapefruit juice consumption, patients older than 70 years of age and those taking multiple medications are at the greatest risk for a serious or fatal interaction with grapefruit juice.

Interaction Rating

Likelihood of Occurrence

Well-controlled human studies have demonstrated the likely existence of this interaction

References

• Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther 1999;66:118-27.
• Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther 1998;64:477-83.
• Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther 2002;71:21-9.
• Fuhr U, Muller-Peltzer H, Kern R, et al. Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Eur J Clin Pharmacol 2002;58:45-53.
• Kanazawa S, Ohkubo T, Sugawara K. The effects of grapefruit juice on the pharmacokinetics of erythromycin. Eur J Clin Pharmacol 2001;56:799-803.
• Charbit, B., Becquemont, L., Lepere, B., Peytavin, G., and Funck-Brentano, C. Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine. Clin Pharmacol Ther 2002;72(5):514-523.
• Tanaka S, Uchida S, Miyakawa S, Inui N, Takeuchi K, Watanabe H, Namiki N. Comparison of inhibitory duration of grapefruit juice on organic anion-transporting polypeptide and cytochrome P450 3A4. Biol Pharm Bull. 2013;36(12):1936-41.
• Bailey DG. Predicting clinical relevance of grapefruit-drug interactions: a complicated process. J Clin Pharm Ther. 2017 Apr;42(2):125-27.
• Mouly S, Lloret-Linares C, Sellire PO, Sene D, Bergmann JF. Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort? Pharmacol Res. 2017 Apr;118:82-92.
• Loretz C, Ho MD, Alam N, Mitchell W, Li AP. Application of cryopreserved human intestinal mucosa and cryopreserved human enterocytes in the evaluation of herb-drug interactions: evaluation of CYP3A inhibitory potential of grapefruit juice and commercial f

Interaction Details

Clomipramine is classified as belonging to the following category: Clomipramine (Anafranil)

Theoretically, grapefruit juice might increase blood levels of clomipramine, potentially increasing the effects and adverse effects of clomipramine.
Case reports have shown that clomipramine trough levels increase significantly after the addition of grapefruit juice to the therapeutic regimen.

Interaction Rating

Likelihood of Occurrence

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.

References

• Oesterheld J, Kallepalli BR. Grapefruit juice and clomipramine: shifting metabolitic ratios. J Clin Psychopharmacol 1997;17:62-3.

Clomipramine Overview

• Clomipramine is used to treat people with obsessive-compulsive disorder (a condition that causes repeated unwanted thoughts and the need to perform certain behaviors over and over). Clomipramine is in a group of medications called tricyclic antidepressants. It works by increasing the amount of serotonin, a natural substance in the brain that is needed to maintain mental balance.

Grapefruit - More Interactions

Grapefruit interacts with 945 drugs

Interaction Rating Key

These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.