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Drug Interactions between ivacaftor / lumacaftor and trimethoprim

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

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Interactions between your drugs

Moderate

trimethoprim lumacaftor

Applies to: trimethoprim and ivacaftor / lumacaftor

MONITOR: Coadministration with potent inducers of CYP450 2C9 and 3A4 may decrease the plasma concentrations of sulfamethoxazole and trimethoprim. A small amount of sulfamethoxazole is metabolized by CYP450 2C9, while trimethoprim is partially metabolized by both CYP450 2C9 and 3A4. In a study of 10 HIV-infected patients receiving sulfamethoxazole-trimethoprim prophylaxis (800 mg-160 mg orally once a day) for at least one month, antituberculosis therapy containing rifampin (600 mg/day) given for more than 12 days decreased mean sulfamethoxazole systemic exposure (AUC) by 23% and mean trimethoprim AUC by 47%, most likely due to induction of hepatic microsomal enzymes by rifampin. The clinical significance of this interaction is unknown, but may be greater with low dosages of sulfamethoxazole-trimethoprim. A case-control study evaluating the effect of sulfamethoxazole-trimethoprim dosage on the risk of toxoplasmosis suggest that rifampin exposure may reduce the efficacy of sulfamethoxazole-trimethoprim prophylaxis. Other potent CYP450 inducers may interact similarly.

MANAGEMENT: The potential for diminished pharmacologic effects of sulfamethoxazole-trimethoprim should be considered during coadministration with potent CYP450 2C9 and 3A4 inducers, particularly when sulfamethoxazole-trimethoprim is used for prevention of toxoplasmic encephalitis in HIV patients because adequate drug levels are required in the central nervous system. It may be advisable to refrain from low-dose prophylactic regimens (less than 4 DS tablets per week). Alternative treatments may be required if an interaction is suspected.

References

  1. Bhatia RS, Uppal R, Malhi R, Behera D, Jindal SK (1991) "Drug interaction between rifampicin and cotrimazole in patients with tuberculosis." Hum Exp Toxicol, 10, p. 419-21
  2. Ribera E, FernandezSola A, Juste C, Rovira A, Romero FJ, ArmadansGil L, Ruiz I, Ocana I, Pahissa A (1999) "Comparison of high and low doses of trimethoprim-sulfamethoxazole for primary prevention of toxoplasmic encephalitis in human immunodeficiency virus-infected patients." Clin Infect Dis, 29, p. 1461-6
  3. Ribera E, Pou L, Fernandez-Sola A, et al. (2001) "Rifampin reduces concentrations of trimethoprim and sulfamethoxazole in serum in human immunodeficiency virus-infected patients." Antimicrob Agents Chemother, 45, p. 3238-41

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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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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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