kaftrio(Trikafta)的药物相互作用是什么？

When using (Trikafta), you need to pay attention to interactions with concomitant drugs to ensure the safety and effectiveness of the drug. Before starting Kaftrio, patients should tell their doctor about all medications they are taking, including prescription drugs, over-the-counter drugs, and supplements. Doctors can evaluate the interactions between these drugs and Kaftrio and adjust the dosage or find safer alternatives if needed.

About kaftrio(Trikafta)

The U.S. FDA approved Trikafta, a new triple combination drug from Vertex Pharmaceuticals, on October 21, 2019, for the treatment of certain types of cystic fibrosis (cystic fibrosis) in people aged 12 years and above. The drug includes Elexacaftor/ivacaftor/tezacaftor and is suitable for CFTR Cystic fibrosis patients who carry at least one copy of the F508del mutation in the gene (ie, the cystic fibrosis transmembrane conductance regulator gene) account for more than 90% of all cystic fibrosis patients.

The possibility of other drugs affecting kaftrio (Trikafta)

1. CYP3A inducer

(1) Elexacaftor, tezacaftor and ivacaftor are substrates of CYP3A (ivacaftor is a sensitive substrate of CYP3A). Concomitant use of CYP3A inducers may result in reduced exposure, thereby reducing the efficacy of TRIKAFTA.

(2) The combination of Elexacaftor and rifampicin (a strong CYP3A inducer) can significantly reduce the area under the curve (AUC) of Elexacaftor by 89%. Reduced exposure to ivacaftor and tezacaftor is expected when coadministered with strong CYP3A inducers.

Therefore, coadministration of TRIKAFTA with strong CYP3A inducers is not recommended.

Examples of strong CYP3A inducers include: rifampicin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John's wort (Hyperforum perforatum).

2. CYP3A inhibitors

(1) When combined with itraconazole, a strong CYP3A inhibitor, the AUC of ivacaftor increased by 2.8 times, and the AUC of tizacaft increased by 4.0-4.5 times.

(2) When itraconazole and ketoconazole were combined, the AUC of Elexacaftor increased by 15.6 times and 8.5 times respectively. The dose of TRIKAFTA should be reduced when coadministered with strong CYP3A inhibitors.

Examples of strong CYP3A inhibitors include: Ketoconazole, itraconazole, posaconazole and voriconazole, telithromycin and clarithromycin.

Simulations indicate that coadministration with moderate CYP3A inhibitors may increase the AUC of ivacaftor and tizacaftor by approximately 1.9-2.3-fold and 2.1-fold, respectively. Coadministration with fluconazole increased the AUC of ivastatin by 2.9-fold. The dose of TRIKAFTA should be reduced when coadministered with moderate CYP3A inhibitors.

Examples of moderate CYP3A inhibitors include: fluconazole, erythromycin.

(3) Coadministration of TRIKAFTA with grapefruit juice containing one or more ingredients that moderately inhibit CYP3A may increase the exposure of elexacaftor, tezacaftor, and ivacaftor; therefore, foods or beverages containing grapefruit should be avoided during treatment with TRIKAFTA.

3. Ciprofloxacin

Ciprofloxacin has no clinically relevant effect on tezacaftor or ivacaftor exposure and is not expected to affect ivacaftor exposure. Therefore, no adjustments are required when TRIKAFTA is administered with ciprofloxacin.

The possibility of kaftrio (Trikafta) specifically affecting other drugs

1. CYP2C9 substrate

Ivacaftor may inhibit CYP2C9; therefore, monitoring of the international normalized ratio (INR) is recommended when TRIKAFTA is coadministered with warfarin. Other drugs that may increase exposure to TRIKAFTA include glimepiride and glipizide; these drugs should be used with caution.

2. P-gp substrate

When ivacaftor or tezacaftor/ivacaftor was coadministered with the sensitive P-gp substrate digoxin, the digoxin AUC increased by 1.3-fold, consistent with ivacaftor's weak inhibitory effect on P-gp. Taking TRIKAFTA may increase the systemic exposure of drugs that are P-gp sensitive substrates, which may increase or prolong their therapeutic effects and adverse effects. Caution and appropriate monitoring should be used when used concurrently with digoxin or other P-gp substrates with a narrow therapeutic index (such as cyclosporine, everolimus, sirolimus, and tacrolimus).

ivacaftor and M23-ELX inhibit the uptake of OATP1B1 and OATP1B3 in vitro. Coadministration with TRIKAFTA may increase exposure to drugs that are substrates of these transporters, such as statins, glyburide, nateglinide, and repaglinide. Caution and appropriate monitoring should be used when used concurrently with OATP1B1 or OATP1B3 substrates.

Recommended hot articles: