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Drug Interactions between darifenacin and imipramine

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

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Interactions between your drugs

Moderate

imipramine darifenacin

Applies to: imipramine and darifenacin

MONITOR: Coadministration with darifenacin may increase the plasma concentrations of drugs that are metabolized by CYP450 2D6, including many psychotherapeutic drugs such as tricyclic antidepressants, phenothiazines, and other neuroleptics. The mechanism is decreased clearance due to inhibition of the CYP450 2D6 isoenzyme by darifenacin. According to the product labeling, darifenacin (30 mg once daily) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of imipramine by 57% and 70%, respectively. These changes were accompanied by a 3.6-fold increase in the mean Cmax and AUC of desipramine, the active metabolite of imipramine. Pharmacodynamically, anticholinergic effects may also increase when darifenacin is used in combination with these drugs. Excessive parasympatholytic effects may result in mydriasis, blurred vision, flushed face, dry skin and mucous membranes, tachycardia, urinary retention, constipation, paralytic ileus, hyperthermia, and heat stroke.

MANAGEMENT: Caution is advised if darifenacin must be used concomitantly with tricyclic antidepressants, phenothiazines, or other neuroleptics. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever darifenacin is added to or withdrawn from therapy. Clinicians should also be alerted to the potential for additive anticholinergic effects during concomitant administration. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations.

References

  1. (2005) "Product Information. Enablex (darifenacin)." Novartis Pharmaceuticals

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Drug and food interactions

Moderate

imipramine food

Applies to: imipramine

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

References

  1. Dorian P, Sellers EM, Reed KL, et al. (1983) "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol, 25, p. 325-31
  2. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R (1983) "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol, 24, p. 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH (1988) "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther, 43, p. 509-18
  5. 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
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF (1990) "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol, 51, p. 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA (1982) "Imipramine disposition in alcoholics." J Clin Psychopharmacol, 2, p. 2-7
View all 7 references

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Minor

darifenacin food

Applies to: darifenacin

The consumption of grapefruit juice may be associated with increased plasma concentrations of darifenacin. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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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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