Pronunciation:
tez-a-kaf-tor/eye-va-kaf-tor
Trade Name(s)
Ther. Class.
cystic fibrosis therapy adjuncts
Pharm. Class.
transmembrane conductance regulator potentiators
Treatment of cystic fibrosis (CF) in patients who are homozygous for the F508del mutation or who have ≥1 mutation in the cystic fibrosis transmembrance conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.
Ivacaftor– acts as a potentiator of the CFTR protein (a chloride channel on the surface of endothelial cells) facilitating chloride transport by increasing the channel-open probability (gating). Tezacaftor– facilitates the cellular processing and trafficking of normal and select mutant forms of CFTR (including F508del-CFTR) to increase the amount of mature CFTR protein delivered to the cell surface.
Therapeutic Effect(s):
Improved lung function.
Tezacaftor
Absorption: Some absorption follows oral administration.
Distribution: Widely distributed to tissues.
Protein Binding: >99%.
Metabolism and Excretion: Primarily metabolized in liver via the CYP3A4 and CYP3A5 isoenzymes; one metabolite (M1) is pharmacologically active; 72% excreted in feces as unchanged drug or metabolite; 14% excreted in urine (primarily as metabolite).
Half-life: 15 hr.
Ivacaftor
Absorption: Some absorption follows oral administration; absorption is enhanced 3-fold by fat-containing foods.
Distribution: Widely distributed to tissues.
Protein Binding: >99%.
Metabolism and Excretion: Primarily metabolized in liver via the CYP3A4 and CYP3A5 isoenzymes; one metabolite (M1) is pharmacologically active; 87.8% eliminated in feces; negligible urinary elimination.
Half-life: 14 hr.
TIME/ACTION PROFILE (plasma concentrations)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
Tezacaftor (PO) | unknown | 4 hr | 12 hr |
Ivacaftor (PO) | unknown | 6 hr | 12 hr |
Contraindicated in:
Use Cautiously in:
CNS: headache, dizziness
EENT: cataracts, sinus congestion
GI: ↑ liver enzymes, nausea
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
Drug-Natural Products:
St. John's wort may ↓ tezacaftor and ivacaftor levels and effectiveness; avoid concurrent use.
Drug-Food:
Grapefruit juice or Seville oranges may ↑ tezacaftor and ivacaftor levels; avoid concurrent use.
PO (Adults and Children ≥12 yr): One tezacaftor 100-mg/ivacaftor 150-mg tablet in AM and one ivacaftor 150-mg tablet in PM (approximately 12 hr apart) with fat-containing food. Concurrent use of strong CYP3A inhibitor– One tezacaftor 100-mg/ivacaftor 150-mg tablet in AM given twice weekly (3–4 days apart). Do not give ivacaftor 150-mg tablet in PM. Concurrent use of moderate CYP3A inhibitor– One tezacaftor 100-mg/ivacaftor 150-mg tablet or one ivacaftor 150-mg tablet on alternate days in the AM. Do not give ivacaftor 150-mg tablet in PM.
Hepatic Impairment
(Adults and Children ≥12 yr): Moderate hepatic impairment (Child-Pugh Class B)– One tezacaftor 100-mg/ivacaftor 150-mg tablet every AM. Do not give ivacaftor 150-mg tablet in PM. Severe hepatic impairment (Child-Pugh Class C)– One tezacaftor 100-mg/ivacaftor 150-mg tablet every AM (or less frequently). Do not give ivacaftor 150-mg tablet in PM.
Tablets: tezacaftor 100 mg/ivacaftor 150 mg (combo) + ivacaftor 100 mg (separate tablets)
Lab Test Considerations:
Monitor ALT and AST before starting therapy and every 3 months during first yr of therapy, and annually thereafter. If ALT or AST >5 x upper limit of normal (ULN), or ALT or AST >3 x ULN with bilirubin >2 x ULN, hold doses until resolution. Consider benefits and risks of resuming therapy.
Improved lung function.