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Drug Interactions between darifenacin and lapatinib

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

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Interactions between your drugs

Moderate

darifenacin lapatinib

Applies to: darifenacin and lapatinib

MONITOR: Coadministration with inhibitors of CYP450 2D6 and/or 3A4 may increase the plasma concentrations of darifenacin, which is a substrate of these isoenzymes. According to the product labeling, coadministration of darifenacin (30 mg once daily) with the mixed CYP450 inhibitor cimetidine resulted in a 42% increase in the mean darifenacin steady-state peak plasma concentration (Cmax) and a 34% increase in the systemic exposure (AUC) compared to administration of darifenacin alone. The potent CYP450 2D6 inhibitor paroxetine (20 mg) increased steady-state AUC of darifenacin (30 mg once daily) by 33%. Erythromycin, a CYP450 3A4 inhibitor, increased the mean steady-state Cmax and AUC of darifenacin (30 mg once daily) by 128% and 95%, respectively. Fluconazole, another 3A4 inhibitor, increased these values by 88% and 84%, respectively.

MANAGEMENT: Pharmacologic response to darifenacin should be monitored more closely whenever a CYP450 2D6 and/or 3A4 inhibitor is added to or withdrawn from therapy, and the darifenacin dosage adjusted if necessary. Patients should be advised to contact their physician if they experience undue adverse effects of darifenacin such as severe abdominal pain or constipation for 3 or more days.

References (2)
  1. (2005) "Product Information. Enablex (darifenacin)." Novartis Pharmaceuticals
  2. (2021) "Product Information. Qelbree (viloxazine)." Supernus Pharmaceuticals Inc

Drug and food interactions

Moderate

lapatinib food

Applies to: lapatinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lapatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

ADJUST DOSING INTERVAL: Food can significantly increase the oral bioavailability of lapatinib. According to the manufacturer, lapatinib peak plasma concentration (Cmax) was approximately 2.5- and 3-fold higher and systemic exposure (AUC) 3- and 4-fold higher when administered with a low fat meal (5% fat; 500 calories) or with a high-fat meal (50% fat; 1000 calories), respectively, compared to fasting. Dividing the daily dose also resulted in an approximately 2-fold higher systemic exposure at steady state compared to the same total dose administered once daily.

MANAGEMENT: Patients treated with lapatinib should preferably avoid the consumption of grapefruit or grapefruit juice. The manufacturer recommends that lapatinib be administered at least one hour before or one hour after a meal. The lapatinib dose is administered once daily and should not be divided.

References (1)
  1. (2007) "Product Information. Tykerb (lapatinib)." Novartis Pharmaceuticals
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)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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.

See also

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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

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