Drug information of tezacaftor/ivacaftor

tezacaftor/ivacaftor

Drug group:

Indicated for cystic fibrosis (CF) in patients who are homozygous for the F508del mutation or who have at least 1 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence

Mechanism of effect

Tezacaftor: CFTR corrector
Ivacaftor: CFTR potentiator

Pharmacodynamic

Tezacaftor: increases amount of mature CFTR protein at the cell surface by targeting the
processing and trafficking defect of the F508del CFTR protein
Ivacaftor: CFTR potentiator; enhances function of the CFTR protein once it reaches the cell surface

Pharmacokinetics

Absorption

Peak plasma time, median at fed state: 4 hr (tezacaftor); 6 hr (ivacaftor)

Peak plasma concentration: 5.95 mcg/mL (tezacaftor); 1.17 mcg/mL (ivacaftor)

AUC: 84.5 mcg·h/mL (tezacaftor); 11.3 mcg·h/mL (ivacaftor)

When administered with fat-containing foods, tezacaftor exposure was similar and ivacaftor exposure was approximately 3 times higher than when taken in a fasting state

Distribution

Protein bound: 99%, primarily to albumin (tezacaftor); 99%, primarily to alpha 1-acid glycoprotein and albumin (ivacaftor)

Vd: 271 L (tezacaftor); 206 L (ivacaftor)

Metabolism

Both tezacaftor and ivacaftor are extensively metabolized in humans, mainly by CYP3A4 and CYP3A5

Elimination

Half-life: 15 hr (tezacaftor); 13.7 hr (ivacaftor)

Clearance: 1.31 L/hr (tezacaftor); 15.7 L/hr (ivacaftor)

Excretion

  • Feces: 72% (tezacaftor); 87.8% (ivacaftor)
  • Urine: 14% (tezacaftor); 6.6% (ivacaftor)

Drug indications

cystic fibrosis patients

Dosage

Adult
Copackaged as a fixed dose combination tablet of tezacaftor 100mg and ivacaftor 150mg
PLUS a separate ivacaftor 150mg tablet

Morning dose: One tezacaftor/ivacaftor 100-mg/150-mg fixed-dose tablet PO

Evening dose: One ivacaftor 150-mg tablet PO

Administer morning and evening doses ~12 hr apart

Pediatric
Copackaged as a fixed-dose combination tablet of tezacaftor 50mg and ivacaftor 75mg PLUS a separate ivacaftor 75mg tablet

<6 years: Safety and efficacy not established

6 to <12 years weighing <30 kg

  • Morning dose: One tezacaftor/ivacaftor 50-mg/75-mg fixed-dose tablet PO
  • Evening dose: One ivacaftor 75-mg tablet PO
  • Administer morning and evening doses ~12 hr apart

≥6 years weighing ≥30 kg

  • Morning dose: One tezacaftor/ivacaftor 100-mg/150-mg fixed-dose tablet PO
  • Evening dose: One ivacaftor 150-mg tablet PO
  • Administer morning and evening doses ~12 hr apart

Side effects

Headache , nausea , vertigo

Alerts

Ivacaftor may elevate liver transaminases; assess ALT and AST before initiating, q3months during first year, and annually thereafter; monitor more frequently in patients with history of elevated transaminases; when transaminases are significantly elevated (eg, ALT/AST >5x ULN, ALT/AST >3x ULN with bilirubin >2x ULN), interrupt dosing and closely monitor until the abnormalities resolve

Noncongenital lens opacities reported in pediatric patients with ivacaftor; baseline and follow-up ophthalmological examinations are recommended before initiating

Points of recommendation

Swallow tablet whole; do not crush, chew, or split

Take at approximately the same time each day about 12 hr apart

Take with fat-containing food (eg, food prepared with butter or oils; food containing eggs, cheeses, nuts, whole milk, or meats)
Store at controlled room temperature (20-25ºC [68-77ºF]); excursions permitted to 15-30ºC (59-86ºF)

Pregnancy level

HAVE NOT BEEN ESTABLISHED

There are limited and incomplete human data from clinical trials and postmarketing reports on the use of tezacaftor and ivacaftor in pregnant women to inform a drug-associated risk

Breast feeding warning

Unknown if distributed in human breast milk

Both tezacaftor and ivacaftor are excreted into the milk of lactating rats

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Drug forms

Symdeko

Ask a Pharmacist


User's questions
    No comments yet.