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Drug Interactions between Adzenys ER and darifenacin

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

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Interactions between your drugs

Moderate

amphetamine darifenacin

Applies to: Adzenys ER (amphetamine) and darifenacin

MONITOR: Coadministration with darifenacin may increase the plasma concentrations of drugs that are metabolized by CYP450 2D6. The mechanism is decreased clearance due to inhibition of the 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 (a CYP450 2D6 substrate) 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. Conversely, some CYP450 2D6 substrates may also increase the plasma concentrations of darifenacin, which is itself metabolized by CYP450 2D6 and may participate in enzymatic competitive inhibition with other substrates.

MANAGEMENT: Caution is advised if darifenacin must be used concomitantly with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever darifenacin is added to or withdrawn from therapy. Pharmacologic response to darifenacin should also be monitored more closely whenever a CYP450 2D6 inhibitor is added to or withdrawn from therapy, and the darifenacin dosage adjusted if necessary. Patients should be advised to contact their doctor if they experience undue adverse effects of darifenacin such as severe abdominal pain or constipation for 3 or more days.

References

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

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Drug and food interactions

Moderate

amphetamine food

Applies to: Adzenys ER (amphetamine)

GENERALLY AVOID: Alcohol may potentiate the cardiovascular effects of amphetamines. The exact mechanism of interaction is unknown. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state. The interaction was suspected in a case report of a 20-year-old male who experienced retrosternal chest pain shortly after drinking alcohol and taking a double dose of his amphetamine/dextroamphetamine medication (Adderall 15 mg X 2) to stay alert. The patient had no family history of cardiovascular diseases, and his past medical history was remarkable only for ADHD. Prior to the episode, the patient had not taken his medication for weeks and had been drinking whiskey the previous three nights before going to bed. The patient was diagnosed with myocardial infarction likely secondary to amphetamine-induced coronary vasospasm.

MANAGEMENT: Concomitant use of amphetamines and alcohol should be avoided if possible, especially in patients with a history of heart disease.

References

  1. Mendelson J, Jones RT, Upton R, Jacob P 3rd (1995) "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther, 57, p. 559-68
  2. Jiao X, Velez S, Ringstad J, Eyma V, Miller D, Bleiberg M (2009) "Myocardial infarction associated with Adderall XR and alcohol use in a young man." J Am Board Fam Med, 22, p. 197-201

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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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