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Drug Interactions between clomipramine and fosphenytoin

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

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Interactions between your drugs

Moderate

clomiPRAMINE fosphenytoin

Applies to: clomipramine and fosphenytoin

MONITOR: Tricyclic antidepressants may increase serum phenytoin levels. In vitro studies suggest the mechanism may involve inhibition of CYP450 2C19-catalyzed phenytoin p-hydroxylation by tricyclic antidepressants, especially imipramine and amitriptyline. Phenytoin may induce the hepatic metabolism of desipramine resulting in decreased plasma concentrations. In addition, tricyclic antidepressants may lower the seizure threshold.

MANAGEMENT: Clinical monitoring of patient response, tolerance, and serum phenytoin concentrations is recommended. Patients should be advised to notify their doctor if they experience loss of seizure control or symptoms of phenytoin toxicity (drowsiness, visual disturbances, change in mental status, nausea, or ataxia). Phenytoin dosage may need to be adjusted.

References (9)
  1. Fogel BS, Haltzman S (1987) "Desipramine and phenytoin: a potential drug interaction of therapeutic relevance." J Clin Psychiatry, 48, p. 387-8
  2. Houghton GW, Richens A (1975) "Inhibition of phenytoin metabolism by other drugs used in epilepsy." Int J Clin Pharmacol, 12, p. 210-6
  3. Perucca E, Richens A (1977) "Interaction between phenytoin and imipramine." Br J Clin Pharmacol, 4, p. 485-6
  4. Shin JG, Park JY, Kim MJ, et al. (2002) "Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin." Drug Metab Dispos, 30, p. 1102-7
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
  8. Cerner Multum, Inc. (2015) "Canadian Product Information."
  9. Cerner Multum, Inc (2015) "ANVISA Bulário Eletrônico."

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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