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Drug Interactions between clomipramine and Quin-Release

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

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Interactions between your drugs

Moderate

quiNIDine clomiPRAMINE

Applies to: Quin-Release (quinidine) and clomipramine

GENERALLY AVOID: Quinidine may markedly increase the serum levels of some tricyclic antidepressants (TCAs). The mechanism is related to inhibition of CYP450 2D6 metabolism. Extensive metabolizers of debrisoquine may be at greater risk of developing significant TCA toxicity. Desipramine, nortriptyline, and imipramine have been specifically implicated in this interaction. In addition, both quinidine and TCAs may cause prolongation of the QT interval which could result in torsades de pointes.

MANAGEMENT: If possible, this combination should be avoided. Close clinical, electrocardiographic, and laboratory monitoring is recommended for patients who do receive these drugs concurrently. Patients should be advised to promptly notify their physicians if they experience irregular heartbeats or palpitations, syncope, drowsiness, confusion, weakness, or seizures.

References

  1. Caporaso NE, Shaw GL "Clinical implications of the competitive inhibition of the debrisoquin-metabolizing isozyme by quinidine." Arch Intern Med 151 (1991): 1985-92
  2. Brosen K, Gram LF "Quinidine inhibits the 2-hydroxylation of imipramine and desipramine but not the demethylation of imipramine." Eur J Clin Pharmacol 37 (1989): 155-60
  3. Steiner E, Dumont E, Spina E, Dahlqvist R "Inhibition of desipramine 2-hydroxylation by quinidine and quinine." Clin Pharmacol Ther 43 (1987): 577-81
  4. von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, Duan SX, Harmatz JS, Shader RI "Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: a model system to predict drug interactions in vivo." J Pharmacol Exp Ther 268 (1994): 1278-83
  5. Roos JC "Cardiac effects of antidepressant drugs. A comparison of the tricyclic antidepressants and fluvoxamine." Br J Clin Pharmacol 15 Suppl 3 (1983): s439-45
View all 5 references

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Drug and food interactions

Moderate

quiNIDine food

Applies to: Quin-Release (quinidine)

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

References

  1. Ace LN, Jaffe JM, Kunka RL "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos 4 (1983): 183-90
  2. Min DI, Ku YM, Geraets DR, Lee HC "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol 36 (1996): 469-76
  3. Ha HR, Chen J, Leuenberger PM, Freiburghaus AU, Follah F "In vitro inhibition of midazolam and quinidine metabolism by flavonoids." Eur J Clin Pharmacol 48 (1995): 367-71
  4. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
View all 4 references

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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

  1. Oesterheld J, Kallepalli BR "Grapefruit juice and clomipramine: shifting metabolitic ratios." J Clin Psychopharmacol 17 (1997): 62-3
  2. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Cerner Multum, Inc. "Australian Product Information." O 0
View all 4 references

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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

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

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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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