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Drug Interactions between Anafranil and cimetidine

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

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Interactions between your drugs

Moderate

cimetidine clomiPRAMINE

Applies to: cimetidine and Anafranil (clomipramine)

MONITOR: Cimetidine may increase the serum concentration of tricyclic antidepressants (TCAs) to toxic levels in some patients. The mechanism may be related to inhibition of CYP450 isoenzymes, including CYP450 2D6 and CYP450 3A4, that are responsible for the hepatic metabolism of TCAs.

MANAGEMENT: Close monitoring for clinical response and tolerance is recommended whenever cimetidine is added to or discontinued from a TCA regimen. Patients should be advised to notify their physician if they experience excessive TCA effects such as dry mouth, blurry vision, irregular or fast heartbeat, constipation, urinary retention, dizziness, or orthostatic hypotension. Lower doses of tricyclic antidepressants may be necessary. Ranitidine, famotidine, and nizatidine are not expected to interact and may be an alternative to cimetidine in this circumstance.

References

  1. Curry SH, DeVane CL, Wolfe MM "Lack of interaction of ranitidine with amitriptyline." Eur J Clin Pharmacol 32 (1987): 317-20
  2. Henauer SA, Hollister LE "Cimetidine interaction with imipramine and nortriptyline." Clin Pharmacol Ther 35 (1984): 183-7
  3. Miller DD, Macklin M "Cimetidine-imipramine interaction: a case report." Am J Psychiatry 140 (1983): 351-2
  4. Abernethy DR, Greenblatt DJ, Shader RI "Imipramine-cimetidine interaction: impairment of clearance and enhanced absolute bioavailability." J Pharmacol Exp Ther 229 (1984): 702-5
  5. Sutherland DL, Remillard AJ, Haight KR, Brown MA, Old L "The influence of cimetidine versus ranitidine on doxepin pharmacokinetics." Eur J Clin Pharmacol 32 (1987): 159-64
  6. Wells BG, Pieper JA, Self TH, et al. "The effect of ranitidine and cimetidine on imipramine disposition." Eur J Clin Pharmacol 31 (1986): 285-90
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. Cerner Multum, Inc. "Australian Product Information." O 0
View all 8 references

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Drug and food interactions

Moderate

clomiPRAMINE food

Applies to: Anafranil (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: Anafranil (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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Minor

cimetidine food

Applies to: cimetidine

Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

References

  1. Feely J, Wood AJ "Effects of cimetidine on the elimination and actions of ethanol." JAMA 247 (1982): 2819-21
  2. Hansten PD "Effects of H2-receptor antagonists on blood alcohol levels." JAMA 267 (1992): 2469

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Minor

cimetidine food

Applies to: cimetidine

Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

References

  1. "Product Information. Tagamet (cimetidine)." SmithKline Beecham PROD (2001):
  2. Broughton LJ, Rodgers HJ "Decreased systenuc clearance of caffeine due to cimetidine." Br J Clin Pharmacol 12 (1981): 155-9

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Minor

cimetidine food

Applies to: cimetidine

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References

  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol 38 (1990): 165-9

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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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