ERMEZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ERMEZA (ERMEZA).
ERMEZA (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 with specific CFTR mutations.
| Metabolism | Primarily metabolized by CYP3A (CYP3A4 and CYP3A5). |
| Excretion | Primarily hepatic metabolism to active metabolite, then renal excretion of metabolites (55-70% in urine) and fecal (25-30%). Unchanged drug in urine <3%. |
| Half-life | Terminal half-life approximately 55 hours (range 44-74 h), allowing once-daily dosing with steady state achieved in 2-3 weeks. |
| Protein binding | >95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 13-29 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: 12-20% due to extensive first-pass metabolism. |
| Onset of Action | Oral: 2-4 weeks for initial therapeutic effect, with maximal impact observed by 4-8 weeks. |
| Duration of Action | Sustained clinical effect persists for at least 24 hours due to long half-life; overall duration of action weeks after discontinuation. |
1.5 mg/kg intravenously over 30 minutes every 4 weeks.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). Not studied in severe renal impairment (GFR <30 mL/min). |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustment recommended; clinical studies included patients aged 65 and older with no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ERMEZA (ERMEZA).
| Breastfeeding | ERMEZA is secreted into human milk; estradiol and levonorgestrel levels are low but may affect milk production and composition. The M/P ratio is not established; however, estradiol has an M/P ratio of approximately 0.5 (range 0.1-0.9) and levonorgestrel approximately 0.5-0.6. Use during lactation is not recommended due to potential adverse effects on the nursing infant, including jaundice and hepatic dysfunction. If used, monitor infant for jaundice and weight gain. |
| Teratogenic Risk | ERMEZA (estradiol and levonorgestrel) is contraindicated in pregnancy. First trimester exposure carries a risk of major congenital malformations, particularly cardiovascular and limb defects, based on animal studies and limited human data. Second and third trimester exposure may lead to urogenital tract abnormalities in female fetuses and feminization of male fetuses. Estrogens have been associated with an increased risk of vaginal adenosis and clear cell adenocarcinoma in female offspring exposed in utero. The drug should be discontinued immediately if pregnancy occurs. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["Hypersensitivity to ivacaftor or any component of the formulation"]
| Precautions | ["Hepatic transaminase elevations: Monitor ALT, AST, and bilirubin at baseline and every 3 months during first year, then annually","Use with strong CYP3A inhibitors: Reduce dose; monitor for adverse reactions","Cataracts: Non-congenital lens opacities reported in pediatric patients; baseline and follow-up ophthalmological examinations recommended","Use in patients with severe hepatic impairment: Not recommended"] |
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| Fetal Monitoring | Monitor maternal blood pressure, liver function tests, and thyroid function periodically. Assess for thromboembolic events (DVT, PE) due to increased risk during pregnancy. Fetal monitoring includes serial growth ultrasounds and nonstress tests if prolonged use occurs. Evaluate for signs of estrogen toxicity or withdrawal in the newborn. In cases of inadvertent first-trimester exposure, offer detailed ultrasound for fetal anatomy. |
| Fertility Effects | ERMEZA temporarily suppresses ovulation as part of its intended mechanism; fertility returns upon discontinuation. Long-term use may cause reversible menstrual irregularities. No permanent impairment of fertility is expected. Advise patients that pregnancy should be avoided during therapy. |