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Drug Interactions between clomipramine and fluconazole

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

fluconazole clomiPRAMINE

Applies to: fluconazole and clomipramine

MONITOR: The coadministration with azole antifungal agents may increase the plasma concentrations of some tricyclic antidepressants (TCAs). Elevated TCA levels may result in CNS toxicity, anticholinergic symptoms, and QT interval prolongation. The mechanism is decreased TCA clearance due to azole-related inhibition of the CYP450 3A4 isoenzyme, which is partially responsible for the metabolism of TCAs like amitriptyline, clomipramine, imipramine, and possibly others. Fluconazole additionally inhibits CYP450 2C19, which is another secondary route of metabolism for several TCAs. The effect of a single dose of fluconazole on TCA pharmacokinetics has not been reported. In a pharmacokinetic study involving six healthy subjects, ketoconazole (200 mg/day for 14 days) increased the half-life and area under the plasma concentration-time curve (AUC) of a single dose of imipramine (100 mg) by 15% and 20%, respectively, but did not affect the pharmacokinetics of desipramine or its metabolite.

MANAGEMENT: During concomitant therapy with azole antifungal agents, patients stabilized on their TCA regimen should be observed for increased pharmacologic response to the TCA, and the dosage adjusted accordingly if necessary. Serum TCA levels should be monitored following initiation or discontinuation of azole antifungal therapy. Patients should be advised to notify their caregiver if they experience excessive dry mouth, visual disturbances, urinary retention, dizziness, syncope, fast or irregular heartbeat, constipation, or seizures.

References (5)
  1. Newberry DL, Bass SN, Mbanefo CO (1997) "A fluconazole/amitriptyline drug interaction in three male adults." Clin Infect Dis, 24, p. 270-1
  2. Spina E, Avenoso A, Campo GM, Scordo MG, Caputi AP, Perucca E (1997) "Effect of ketoconazole on the pharmacokinetics of imipramine and desipramine in healthy subjects." Br J Clin Pharmacol, 43, p. 315-8
  3. Gannon RH (1992) "Fluconazole-nortriptyline drug interaction." Ann Pharmacother, 26, p. 1456
  4. Robinson RF, Nahata MC, Olshefski RS (2000) "Syncope associated with concurrent amitriptyline and fluconazole therapy." Ann Pharmacother, 34, p. 1406-9
  5. Dorsey ST, Biblio LA (2000) "Prolonged QT interval and torsades de pointes caused by the combination of fluconazole and amitriptyline." Am J Emerg Med, 18, p. 227-9

Drug and food interactions

Moderate

clomiPRAMINE food

Applies to: clomipramine

MONITOR: Limited data suggest that the administration of clomipramine with grapefruit juice or cranberry juice may significantly increase plasma drug concentrations of clomipramine. Clomipramine is initially demethylated by CYP450 1A2, 3A3 and 3A4 before undergoing further metabolism to 8-hydroxyclomipramine. The increase in clomipramine bioavailability may stem from inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The precise mechanism by which cranberry juice exerts its effects is unknown, but may involve inhibition of CYP450 isoenzymes. This interaction has occasionally been exploited in attempts to improve symptomatic control of obsessive compulsive disorder.

MANAGEMENT: Patients receiving clomipramine therapy who ingest cranberry juice, grapefruits, or grapefruit juice should be monitored for adverse effects and undue fluctuations in plasma drug levels.

References (4)
  1. Oesterheld J, Kallepalli BR (1997) "Grapefruit juice and clomipramine: shifting metabolitic ratios." J Clin Psychopharmacol, 17, p. 62-3
  2. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."
Moderate

clomiPRAMINE food

Applies to: clomipramine

GENERALLY AVOID: The combination of ethanol and a tricyclic antidepressant may result in additive impairment of motor skills, especially driving skills. Also, one study has suggested that clomipramine metabolism is significantly impaired for several weeks or more following discontinuation of chronic alcohol consumption.

MANAGEMENT: Patients should be warned of this interaction and advised to limit their ethanol intake while taking tricyclic antidepressants. Monitoring for TCA toxicity (CNS depression, excessive anticholinergic effects, hypotension, arrhythmias) is recommended during alcohol withdrawal.

References (3)
  1. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M (1975) "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther, 17, p. 515-22
  2. Berlin I, Cournot A, Zimmer R, et al. (1990) "Evaluation and comparison of the interaction between alcohol and moclobemide or clomipramine in healthy subjects." Psychopharmacology (Berl), 100, p. 40-5
  3. Balant-Gorgia AE, Gay M, Gex-Fabry M, Balant LP (1992) "Persistent impairment of clomipramine demethylation in recently detoxified alcoholic patients." Ther Drug Monit, 14, p. 119-24

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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