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Drug Interaction Report

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

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Interactions between your drugs

Moderate

ivacaftor xanomeline

Applies to: elexacaftor / ivacaftor / tezacaftor, 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

ivacaftor food

Applies to: elexacaftor / ivacaftor / tezacaftor

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Elexacaftor and tezacaftor are also CYP450 3A4 substrates in vitro and may interact similarly with grapefruit juice, whereas lumacaftor is not expected to interact.

ADJUST DOSING INTERVAL: According to prescribing information, systemic exposure to ivacaftor increased approximately 2.5- to 4-fold, systemic exposure to elexacaftor increased approximately 1.9- to 2.5-fold, and systemic exposure to lumacaftor increased approximately 2-fold following administration with fat-containing foods relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with ivacaftor-containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit or Seville oranges. All ivacaftor-containing medications should be administered with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products. A typical cystic fibrosis diet will satisfy this requirement.

References (4)
  1. (2012) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals
  2. (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
  3. (2022) "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals
  4. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
Moderate

tezacaftor food

Applies to: elexacaftor / ivacaftor / tezacaftor

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of tezacaftor, deutivacaftor, and vanzacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. 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. The risk and/or severity of serious side effects such as liver damage may be increased.

ADJUST DOSING INTERVAL: Administration with fat-containing food may increase the oral bioavailability of vanzacaftor and deutivacaftor. Administration with a fat containing meal increased vanzacaftor systemic exposure (AUC) by 4- (low-fat meal) to 6- (high-fat meal) fold. While deutivacaftor AUC increased approximately 3- (low-fat meal) to 4- (high-fat meal) fold, relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with tezacaftor, deutivacaftor, vanzacaftor -containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit. To improve absorption, patients should be advised to take vanzacaftor and/or deutivacaftor containing medications with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products at approximately the same time of the day. A typical cystic fibrosis diet will satisfy this requirement.

References (6)
  1. (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  2. (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
  3. (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
  4. (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
  5. (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
  6. (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals

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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Further information

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