Trikafta Oral Granules

— THERAPEUTIC CATEGORIES —
  • Inborn errors of metabolism
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Trikafta Oral Granules Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Elexacaftor, tezacaftor, ivacaftor; 80mg/40mg/60mg with ivacaftor 59.5mg; 100mg/50mg/75mg with ivacaftor 75mg; packets.

    Pharmacological Class

    Cystic fibrosis transmembrane conductance regulator (CFTR) corrector + CFTR potentiator.

    See Also

    How Supplied

    Tabs—84 (4×21); Oral granules—56 (4×14)

     

    Manufacturer

    Vertex Pharmaceuticals

    Generic Availability

    NO

    Mechanism of Action

    Elexacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of F508del-CFTR to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect is increased quantity and function of F508del-CFTR at the cell surface, resulting in increased CFTR activity as measured by CFTR mediated chloride transport.

    Trikafta Oral Granules Indications

    Indications

    Cystic fibrosis (CF) in patients ≥2yrs who have at least one F508del mutation in the CFTR gene or a mutation in the CFTR gene that is responsive based on in vitro data.

    Trikafta Oral Granules Dosage and Administration

    Adult

    Swallow tabs whole. Take with fat-containing food (eg, eggs, cheeses, nuts, whole milk, meats). ≥12yrs: 2 tabs (100mg/50mg/75mg) in the AM and 1 tab (ivacaftor 150mg) in the PM, approx. 12hrs apart. Moderate hepatic impairment (not recommended; if needed, use with caution at reduced dose), concomitant moderate or strong CYP3A inhibitors: see full labeling.

    Children

    <2yrs: not established. Oral granules: mix contents of each packet with 5mL of age-appropriate soft food or liquid at or below room temperature (eg, pureed fruits/vegetables, yogurt, applesauce, water, milk, juice); consume within 1hr. Take with fat-containing food (eg, eggs, peanut butter, cheeses, nuts, whole milk, meats). 2–<6yrs (<14kg): 1 packet (80mg/40mg/60mg) oral granules in the AM and 1 packet (ivacaftor 59.5mg) oral granules in the PM, approx. 12hrs apart; (≥14kg): 1 packet (100mg/50mg/75mg) oral granules in the AM and 1 packet (ivacaftor 75mg) oral granules in the PM, approx. 12hrs apart. Swallow tabs whole. 6–<12yrs (<30kg): 2 tabs (50mg/25mg/37.5mg) in the AM and 1 tab (ivacaftor 75mg) in the PM, approx. 12hrs apart; (≥30kg): 2 tabs (100mg/50mg/75mg) in the AM and 1 tab (ivacaftor 150mg) in the PM, approx. 12hrs apart. Moderate hepatic impairment (not recommended; if needed, use with caution at reduced dose), concomitant moderate or strong CYP3A inhibitors: see full labeling.

    Trikafta Oral Granules Contraindications

    Not Applicable

    Trikafta Oral Granules Boxed Warnings

    Not Applicable

    Trikafta Oral Granules Warnings/Precautions

    Warnings/Precautions

    If genotype is unknown, use an FDA-cleared CF mutation test to confirm the presence of at least 1 F508del mutation. Pre-existing advanced liver disease (eg, cirrhosis, portal hypertension, ascites, hepatic encephalopathy): avoid. Assess ALT/AST and bilirubin levels prior to initiation, every 3 months during the first year of treatment, and annually thereafter. Interrupt dosing and monitor closely if ALT/AST elevations >5×ULN or ALT/AST >3×ULN with bilirubin >2×ULN; after resolution, consider resuming therapy. History of hepatobiliary disease or LFT elevations; consider more frequent monitoring. Perform baseline and follow-up eye exams. Moderate hepatic impairment: see Adult, Children. Severe hepatic impairment: do not use. Severe renal impairment or ESRD. Pregnancy. Nursing mothers.

    Trikafta Oral Granules Pharmacokinetics

    Metabolism

    CYP3A4/5. ≥99% protein binding.

    Elimination

    Fecal (major), renal. Half-life (effective): 27.4 hours ± 9.31 (elexacaftor); 25.1 hours ± 4.93 (tezacaftor); 15 hours ± 3.92 (ivacaftor).

    Trikafta Oral Granules Interactions

    Interactions

    Potentiated by strong (eg, ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin) or moderate (eg, fluconazole, erythromycin) CYP3A inhibitors; adjust dose. Avoid food or drink containing grapefruit. Antagonized by strong CYP3A inducers (eg, rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort); use not recommended. Caution with concomitant CYP2C9 substrates (eg, warfarin, glimepiride, glipizide), digoxin or other P-gp substrates with a narrow therapeutic index (eg, cyclosporine, everolimus, sirolimus, tacrolimus), OATP1B1 or OATP1B3 substrates (eg, statins, glyburide, nateglinide, repaglinide); monitor.

    Trikafta Oral Granules Adverse Reactions

    Adverse Reactions

    Headache, upper respiratory tract infection, abdominal pain, diarrhea, rash, ALT/AST increased, nasal congestion, blood CPK increased, rhinorrhea, rhinitis, influenza, sinusitis, blood bilirubin increased; non-congenital lens opacities/cataracts, hepatic injury.

    Trikafta Oral Granules Clinical Trials

    See Literature

    Trikafta Oral Granules Note

    Not Applicable

    Trikafta Oral Granules Patient Counseling

    See Literature

    Images

    • Latest News Your top articles for Wednesday

    • Haymarket Medical NetworkTop Picks

    • Loading...

      Continuing Medical Education (CME/CE) Courses

      Show More