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Drug Interactions between cobimetinib and ivacaftor

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

ivacaftor cobimetinib

Applies to: ivacaftor and cobimetinib

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations of cobimetinib, which is a substrate of both the isoenzyme and the efflux transporter. In 15 healthy volunteers given a single 10 mg dose of cobimetinib with the potent CYP450 3A4 and P-gp inhibitor itraconazole (200 mg once daily for 14 days), mean cobimetinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3.2- and 6.7-fold, respectively, compared to cobimetinib administered alone. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that steady-state concentrations of cobimetinib given at a reduced dose of 20 mg with short-term (less than 14 days) use of a moderate CYP450 3A4 inhibitor would be similar to steady-state concentrations observed following a 60 mg dose given alone.

MANAGEMENT: Caution is advised when cobimetinib is prescribed with CYP450 3A4 and/or P-gp inhibitors. Patients should be monitored for adverse effects such as diarrhea, nausea, vomiting, stomatitis, hemorrhage, cardiomyopathy, rash, photosensitivity, retinopathy, retinal vein occlusion, liver enzyme abnormalities and rhabdomyolysis, and the cobimetinib dosage adjusted accordingly or treatment discontinued as necessary.

References

  1. "Product Information. Cotellic (cobimetinib)." Genentech (2015):

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Drug and food interactions

Moderate

ivacaftor food

Applies to: ivacaftor

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

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

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Moderate

cobimetinib food

Applies to: cobimetinib

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme, such as cobimetinib. However, the interaction seems to affect primarily those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability), presumably due to the fact that grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of cobimetinib. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "Product Information. Cotellic (cobimetinib)." Genentech (2015):

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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.

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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.

Further information

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

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