Drug Interaction Report
3 potential interactions and/or warnings found for the following 2 drugs:
- venetoclax
- trospium / xanomeline
Interactions between your drugs
venetoclax xanomeline
Applies to: venetoclax, 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)
- (2024) "Product Information. Cobenfy (trospium-xanomeline)." Bristol-Myers Squibb
Drug and food interactions
venetoclax food
Applies to: venetoclax
ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of venetoclax. Relative to fasting conditions, venetoclax systemic exposure (AUC) increased by approximately 3.4-fold when administered with a low-fat meal (approximately 512 kilocalories, 25% calories from fat) and by 5.1- to 5.3-fold when administered with a high-fat meal (approximately 753 kilocalories, 55% calories from fat).
GENERALLY AVOID: Grapefruit, grapefruit juice, Seville oranges, and starfruit may increase the plasma concentrations of venetoclax, which is primarily metabolized by the CYP450 3A4 isoenzyme. 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 juice, but has been reported with potent CYP450 3A4 inhibitors. In a study of 11 previously treated non-Hodgkin lymphoma patients, when the potent CYP450 3A4 inhibitor, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitor ketoconazole (400 mg daily for 7 days) was coadministered with venetoclax (50 mg single dose), venetoclax peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.3-fold and 6.4-fold, respectively. Physiologically based pharmacokinetic modeling estimates that the moderate CYP450 3A4 inhibitors diltiazem and erythromycin may increase the Cmax and AUC of venetoclax by between 1.4- to 2- fold and 2- to 4.9-fold, respectively, while the weak CYP450 3A4 inhibitors fluoxetine and fluvoxamine appear to have no significant effect on its Cmax or AUC. 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. Increased venetoclax exposure may potentiate the risk of tumor lysis syndrome, particularly at initiation of therapy and during the dosage ramp-up phase, as well as other adverse effects such as diarrhea, nausea, vomiting, neutropenia, anemia, and thrombocytopenia.
MANAGEMENT: Venetoclax should be administered with a meal and water at approximately the same time each day. Patients should avoid consumption of grapefruit products, Seville oranges, and starfruit during treatment with venetoclax.
References (6)
- (2016) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
- (2022) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
- (2023) "Product Information. Venclexta (venetoclax)." AbbVie Pty Ltd
- (2024) "Product Information. Venclyxto (venetoclax)." AbbVie Ltd
- (2022) "Product Information. Venclexta (venetoclax)." AbbVie Corporation
- Freise K.J, Shebley M, Salem A.H (2017) "Quantitative prediction of the effect of CYP3A inhibitors and inducers on venetoclax pharmacokinetics using a physiologically based pharmacokinetic model" J Clin Pharmacol, 57, p. 796-804
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)
- (2012) "Product Information. Sanctura (trospium)." Odyssey Pharmaceuticals
- (2024) "Product Information. Cobenfy (trospium-xanomeline)." Bristol-Myers Squibb
- (2019) "Product Information. Trosec (trospium)." Oryx Pharmaceuticals Inc
- (2022) "Product Information. Regurin (trospium)." Mylan Healthcare Sdn. Bhd.
- (2023) "Product Information. Trospium Chloride (trospium)." Padagis
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.
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. |
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