Drug Interactions between ivacaftor / lumacaftor and venetoclax
This report displays the potential drug interactions for the following 2 drugs:
- ivacaftor/lumacaftor
- venetoclax
Interactions between your drugs
ivacaftor venetoclax
Applies to: ivacaftor / lumacaftor and venetoclax
GENERALLY AVOID: Coadministration with P-glycoprotein (P-gp) inhibitors may increase the plasma concentrations of venetoclax, which is a substrate of this efflux transporter. Administration of venetoclax with a single dose of rifampin, a P-gp inhibitor when given acutely, increased venetoclax Cmax by 106% and AUC by 78%. 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: Concomitant use of venetoclax with P-gp inhibitors should generally be avoided. If coadministration is required, the manufacturer recommends that venetoclax dosage be reduced by at least 50%. The dosage used prior to initiating the P-gp inhibitor may be resumed 2 to 3 days after discontinuation of the inhibitor.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2016) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
lumacaftor venetoclax
Applies to: ivacaftor / lumacaftor and venetoclax
GENERALLY AVOID: Coadministration with potent and moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of venetoclax, which is primarily metabolized by the isoenzyme. In 10 healthy volunteers, venetoclax peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 42% and 71%, respectively, when coadministered with 600 mg once daily for 13 days of rifampin, a potent CYP450 3A4 inducer. Therapeutic failure may occur.
MANAGEMENT: Concomitant use of venetoclax with potent and moderate CYP450 3A4 inducers should generally be avoided. Alternative agents with no or minimal CYP450 3A4 induction potential are recommended whenever possible.
References
- (2016) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
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 and by 5.1- to 5.3-fold when administered with a high-fat meal.
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of venetoclax. 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. 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
- (2016) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
ivacaftor food
Applies to: ivacaftor / lumacaftor
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
- (2012) "Product Information. Kalydeco (ivacaftor)." Vertex Pharmaceuticals
- (2015) "Product Information. Orkambi (ivacaftor-lumacaftor)." Vertex Pharmaceuticals
- (2022) "Product Information. Symdeko (ivacaftor-tezacaftor)." Vertex Pharmaceuticals
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
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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