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Drug Interactions between ivacaftor / lumacaftor and Mavyret

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

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Interactions between your drugs

Moderate

lumacaftor glecaprevir

Applies to: ivacaftor / lumacaftor and Mavyret (glecaprevir / pibrentasvir)

MONITOR: Coadministration with inducers of P-glycoprotein (P-gp) or CYP450 3A4 may decrease the plasma concentrations of glecaprevir and pibrentasvir. Both antiviral agents are substrates of the P-gp efflux transporter, and glecaprevir is additionally a substrate of the CYP450 3A4 isoenzyme. When a single 300 mg-120 mg dose of glecaprevir-pibrentasvir was administered to 12 study subjects following multiple dosing of the potent inducer rifampin at 600 mg once daily, glecaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 86% and 88%, respectively, while pibrentasvir Cmax and AUC decreased by 83% and 87%, respectively. Likewise, when a single dose of glecaprevir-pibrentasvir was administered to 10 study subjects following multiple dosing of carbamazepine 200 mg twice daily, glecaprevir Cmax and AUC decreased by approximately two-thirds, while pibrentasvir Cmax and AUC decreased by approximately one-half.

MANAGEMENT: The potential for diminished pharmacologic effects of glecaprevir and pibrentasvir should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

References

  1. (2017) "Product Information. Mavyret (glecaprevir-pibrentasvir)." Abbott Pharmaceutical

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Drug and food interactions

Moderate

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

  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
View all 4 references

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Moderate

glecaprevir food

Applies to: Mavyret (glecaprevir / pibrentasvir)

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of glecaprevir and pibrentasvir. Relative to fasting conditions, mean glecaprevir systemic exposure (AUC) increased by 83% to 163% and mean pibrentasvir AUC increased by 40% to 53% when administered with moderate to high fat meals.

MANAGEMENT: Glecaprevir-pibrentasvir should be administered with food.

References

  1. (2017) "Product Information. Mavyret (glecaprevir-pibrentasvir)." Abbott Pharmaceutical

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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.

See also

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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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