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Drug Interaction Report

3 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Moderate

ubrogepant xanomeline

Applies to: ubrogepant, trospium / xanomeline

MONITOR: Xanomeline may increase the concentration of sensitive oral CYP450 3A4 substrates and/or narrow therapeutic index (NTI) oral P-glycoprotein (P-gp) substrates. In vitro data suggest that xanomeline may transiently inhibit CYP450 3A4 and P-gp locally in the intestine after dosing. Xanomeline does not appear to inhibit CYP450 3A4 and/or P-gp systemically. Clinical data evaluating this interaction are not available.

MANAGEMENT: Caution and clinical monitoring are advised if xanomeline is used in combination with an orally administered CYP450 3A4 sensitive substrate and/or NTI P-gp substrate for which a small change in substrate plasma concentration could lead to serious toxicities. The labeling of the substrate may be consulted for specific monitoring and dose adjustment recommendations should adverse reactions result from this combination.

References (1)
  1. (2024) "Product Information. Cobenfy (trospium-xanomeline)." Bristol-Myers Squibb

Drug and food interactions

Moderate

trospium food

Applies to: trospium / xanomeline

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of trospium chloride. According to the product labeling, administration of trospium chloride with a high fat meal reduced the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 70% to 80% compared to administration while fasting.

MANAGEMENT: To ensure maximal oral absorption, trospium chloride should be administered at least 1 hour before meals or on an empty stomach. If trospium chloride is administered as a combination with xanomeline, the manufacturer recommends administering the capsules at least 1 hour before a meal or at least 2 hours after a meal. Capsules should be taken whole.

References (5)
  1. (2012) "Product Information. Sanctura (trospium)." Odyssey Pharmaceuticals
  2. (2024) "Product Information. Cobenfy (trospium-xanomeline)." Bristol-Myers Squibb
  3. (2019) "Product Information. Trosec (trospium)." Oryx Pharmaceuticals Inc
  4. (2022) "Product Information. Regurin (trospium)." Mylan Healthcare Sdn. Bhd.
  5. (2023) "Product Information. Trospium Chloride (trospium)." Padagis
Moderate

ubrogepant food

Applies to: ubrogepant

ADJUST DOSE: Grapefruit and grapefruit juice may increase the plasma concentrations of ubrogepant. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit but has been reported for other CYP450 3A4 inhibitors. When ubrogepant was administered with the potent CYP450 3A4 inhibitor ketoconazole during in vivo studies, ubrogepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 5.3- and 9.7-fold, respectively. When administered with the moderate CYP450 3A4 inhibitor verapamil, ubrogepant Cmax and AUC increased by 2.8- and 3.5-fold, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

When administered with a high-fat meal, ubrogepant time to maximum plasma concentration (Tmax) was delayed by 2 hours, which resulted in a 22% decrease in Cmax and no change in AUC. Ubrogepant was administered without regard to food in clinical efficacy studies.

MANAGEMENT: Ubrogepant may be administered with or without food. When coadministered with grapefruit or grapefruit juice, the manufacturer recommends an initial ubrogepant dose of 50 mg. A second dose, if needed, should not be administered within 24 hours of the initial dose.

References (1)
  1. (2019) "Product Information. Ubrelvy (ubrogepant)." Allergan Inc

Therapeutic duplication warnings

No duplication 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.

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Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.