IVACAFTOR
Clinical safety rating: safe
Animal studies have demonstrated safety
Ivacaftor is a CFTR potentiator that increases the open probability of the cystic fibrosis transmembrane conductance regulator (CFTR) protein at the cell surface, enhancing chloride transport in epithelial cells. It is effective in CFTR mutations with residual function or responsive to potentiators.
| Metabolism | Primarily metabolized by CYP3A4 and CYP3A5. Ivacaftor is extensively metabolized in the liver with less than 1% excreted unchanged in urine. |
| Excretion | Primarily fecal (87%) as unchanged drug and metabolites; renal excretion accounts for <1% |
| Half-life | 12-14 hours in healthy subjects; steady state achieved in 3-5 days |
| Protein binding | 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 3.1-3.6 L/kg, suggesting extensive extravascular distribution |
| Bioavailability | Not applicable; administered intravenously (no oral bioavailability as ivacaftor alone; oral bioavailability is from combination products) |
| Onset of Action | Not applicable; therapeutic effect on CFTR function is cumulative over days to weeks |
| Duration of Action | Dosing every 12 hours maintains therapeutic levels; effect persists as long as drug is present |
150 mg orally every 12 hours with fat-containing food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m2); use with caution. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: 150 mg once daily. Child-Pugh Class C: not recommended. |
| Pediatric use | Children 6 years and older weighing ≥25 kg: 150 mg orally every 12 hours with fat-containing food. |
| Geriatric use | No specific dose adjustment; use with caution due to age-related renal and hepatic decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause elevated liver enzymes and non-congenital cataracts.
| Breastfeeding | No human data; ivacaftor enters rat milk. Consider developmental benefits vs risks; M/P ratio unknown. |
| Teratogenic Risk | Insufficient human data; animal studies show no evidence of fetal harm at exposures up to 4 times the human exposure. Avoid in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor liver function tests (ALT, AST) and pulmonary function. Fetal monitoring per standard obstetric care. |
■ FDA Black Box Warning
No FDA black box warnings.
| Common Effects | Headache |
| Serious Effects |
["Hypersensitivity to ivacaftor or any excipients"]
| Precautions | ["Hepatotoxicity: Elevated transaminases and hepatic injury; monitor liver function tests before and during treatment.","Cataracts: Non-congenital lens opacities have been reported in pediatric patients; baseline and follow-up ophthalmological exams are recommended.","Drug interactions: Strong inhibitors of CYP3A (e.g., ketoconazole) reduce ivacaftor clearance, requiring dose reduction; strong inducers (e.g., rifampin) may decrease efficacy.","Use in pregnancy: Limited data; consider risks and benefits."] |
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| Fertility Effects | No adverse effects on fertility observed in animal studies. Human data lacking. |