Drug Interactions between cobicistat / darunavir and darifenacin
This report displays the potential drug interactions for the following 2 drugs:
- cobicistat/darunavir
- darifenacin
Interactions between your drugs
darifenacin cobicistat
Applies to: darifenacin and cobicistat / darunavir
ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of darifenacin, which is partially metabolized by the isoenzyme. Darifenacin is also metabolized by CYP450 2D6, but 3A4 is the major pathway of metabolism in so-called poor metabolizers of 2D6 (approximately 7% of Caucasians and 2% of Asians and those of African descent). In a drug interaction study involving 10 extensive metabolizers and 1 poor metabolizer of 2D6, coadministration with the potent 3A4 inhibitor ketoconazole (400 mg) increased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of darifenacin (extended-release 7.5 mg once a day) approximately 5-fold each compared to values previously reported for extensive metabolizers of 2D6. In the poor metabolizer, Cmax and AUC of darifenacin increased approximately 13-fold each compared to values previously reported for poor metabolizers. When a 15 mg daily dose of extended-release darifenacin was given with ketoconazole, mean darifenacin Cmax and AUC in 3 extensive metabolizers increased approximately 12-fold compared to historical values, while Cmax and AUC increased approximately 6-fold in the poor metabolizer compared to historical values.
MANAGEMENT: The dosage of darifenacin should not exceed 7.5 mg/day when used with potent CYP450 3A4 inhibitors. Some authorities recommend avoiding concomitant use of darifenacin during and for 2 weeks after treatment with itraconazole.
References
- (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
- (2005) "Product Information. Enablex (darifenacin)." Novartis Pharmaceuticals
- Cerner Multum, Inc. "Australian Product Information."
- Niwa T, Shiraga T, Takagi A (2005) "Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, CYP3A4 activities in human liver microsomes." Biol Pharm Bull, 28, p. 1805-8
darifenacin darunavir
Applies to: darifenacin and cobicistat / darunavir
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
- (2005) "Product Information. Enablex (darifenacin)." Novartis Pharmaceuticals
- (2021) "Product Information. Qelbree (viloxazine)." Supernus Pharmaceuticals Inc
Drug and food interactions
darunavir food
Applies to: cobicistat / darunavir
ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).
MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.
References
- (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
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
- 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
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
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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