Ivacaftor
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Dosing in kidney impairment
Renal Impairment KALYDECO has not been studied in patients with mild, moderate, or severe renal impairment or in patients with end-stage renal disease. No dosage adjustment is necessary for patients with mild to moderate renal impairment; however, caution is recommended while using KALYDECO in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/min) or end-stage renal disease.
Dosing in liver impairment
Recommended Dosage for Patients with Hepatic Impairment KALYDECO is not recommended in patients less than 6 months of age with any level of hepatic impairment. The following is the recommended dosage of KALYDECO taken with fat-containing food [see Dosage and Administration ] for patients aged 6 months and older with hepatic impairment: Mild Hepatic Impairment (Child-Pugh Class A): Less than 6 months of age: KALYDECO is not recommended.
No dosage adjustment is necessary for patients aged 6 months or older [see Clinical Pharmacology ] . Moderate Hepatic Impairment (Child-Pugh Class B): Less than 6 months of age: KALYDECO is not recommended. 6 months to less than 6 years of age: one packet (containing 25 mg, 50 mg, or 75 mg ivacaftor) of oral granules once daily based on dosing recommended for age and weight in Table 1 [see Dosage and Administration ]. 6 years of age and older: 150 mg orally once daily.
Severe Hepatic Impairment (Child-Pugh Class C): Should not be used in patients less than 6 months of age. In patients aged 6 months and older should be used with caution. KALYDECO has not been studied in patients with severe hepatic impairment (Child-Pugh Class C), but exposure is expected to be higher than in patients with moderate hepatic impairment.
Therefore, use with caution at a reduced dosage, in patients aged 6 months or older with severe hepatic impairment after weighing the risks and benefits of treatment [see Dosage and Administration (2.1 , 2.2) and Clinical Pharmacology ] . Less than 6 months of age: KALYDECO is not recommended. 6 months to less than 6 years of age: one packet (containing 25 mg, 50 mg, or 75 mg ivacaftor) of oral granules once daily or less frequently based on dosing recommended for age and weight in Table 1 [see Dosage and Administration ]. 6 years of age and older: 150 mg orally once daily or less frequently.
Preparation and administration
Administration Information Administer KALYDECO tablets or oral granules with fat-containing food. Examples include eggs, butter, peanut butter, cheese pizza, whole-milk dairy products (such as whole milk, cheese, yogurt, breast milk, or infant formula), etc. [see Clinical Pharmacology ]. Instruction for Administration of Tablets Swallow tablets whole.
Instruction for Administration of Oral Granules Administer each dose of KALYDECO oral granules immediately before or after ingestion of fat-containing food. Mix the entire contents of each packet of oral granules with one teaspoon (5 mL) of age-appropriate soft food or liquid that is at or below room temperature. Some examples of soft foods or liquids may include puréed fruits or vegetables, yogurt, applesauce, water, breast milk, infant formula, milk, or juice.
Food or liquid should be at or below room temperature. Once mixed, the product should be completely consumed within one hour.
Drug interactions
Check ivacaftor against a medication listLabel text (9 paragraphs)
Potential for other drugs to affect ivacaftor CYP3A inhibitors: Reduce KALYDECO dosage in patients aged 6 months and older when co-administered with strong CYP3A inhibitors (e.g., ketoconazole) or moderate CYP3A inhibitors (e.g., fluconazole). KALYDECO is not recommended in patients aged 1 month to less than 6 months when co-administered with strong or moderate CYP3A inhibitors. Avoid food or drink containing grapefruit. ( 2.4 , 7.1 )
7.1 Inhibitors of CYP3A Ivacaftor is a sensitive CYP3A substrate. Co-administration with ketoconazole, a strong CYP3A inhibitor, significantly increased ivacaftor exposure [measured as area under the curve (AUC)] by 8.5-fold. Based on simulations of these results, a reduction of the KALYDECO dosage is recommended for patients aged 6 months and older taking concomitant strong CYP3A inhibitors, such as ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin. KALYDECO is not recommended for patients less than 6 months of age taking strong CYP3A inhibitors [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ] .
Co-administration with fluconazole, a moderate inhibitor of CYP3A, increased ivacaftor exposure by 3-fold. Therefore, a reduction of the KALYDECO dosage is recommended for patients aged 6 months and older taking concomitant moderate CYP3A inhibitors, such as fluconazole and erythromycin. KALYDECO is not recommended for patients less than 6 months of age taking moderate CYP3A inhibitors [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ] . Co-administration of KALYDECO with grapefruit juice, which contains one or more components that moderately inhibit CYP3A, may increase exposure of ivacaftor.
Therefore, avoid food or drink containing grapefruit during treatment with KALYDECO [ see Clinical Pharmacology (12.3) ].
7.2 Inducers of CYP3A Co-administration with rifampin, a strong CYP3A inducer, significantly decreased ivacaftor exposure (AUC) by approximately 9-fold. Therefore, co-administration with strong CYP3A inducers, such as rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John's wort is not recommended [ see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3) ].
7.3 Ciprofloxacin Co-administration of KALYDECO with ciprofloxacin had no effect on the exposure of ivacaftor. Therefore, no dosage adjustment is necessary during concomitant administration of KALYDECO with ciprofloxacin [ see Clinical Pharmacology (12.3) ]. Potential for ivacaftor to affect other drugs
7.4 CYP2C9 Substrates Ivacaftor may inhibit CYP2C9; therefore, monitoring of the international normalized ratio (INR) during co-administration of KALYDECO with warfarin is recommended. Other therapeutic products for which exposure may be increased by KALYDECO include glimepiride and glipizide; these therapeutic products should be used with caution [see Clinical Pharmacology (12.3) ] .
7.5 CYP3A and/or P-gp Substrates Ivacaftor and its M1 metabolite have the potential to inhibit CYP3A and P-gp. Co-administration with oral midazolam, a sensitive CYP3A substrate, increased midazolam exposure 1.5-fold, consistent with weak inhibition of CYP3A by ivacaftor. Co-administration with digoxin, a sensitive P-gp substrate, increased digoxin exposure by 1.3-fold, consistent with weak inhibition of P-gp by ivacaftor. Administration of KALYDECO may increase systemic exposure of drugs that are substrates of CYP3A and/or P-gp, which may increase or prolong their therapeutic effect and adverse events.
Therefore, caution and appropriate monitoring are recommended when co-administering KALYDECO with sensitive CYP3A and/or P-gp substrates, such as digoxin, cyclosporine, and tacrolimus [ see Clinical Pharmacology (12.3) ].
Contraindications
None. None ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary There are limited and incomplete human data from clinical trials and postmarketing reports on use of KALYDECO in pregnant women. In animal reproduction studies, oral administration of ivacaftor to pregnant rats and rabbits during organogenesis demonstrated no teratogenicity or adverse effects on fetal development at doses that produced maternal exposures up to approximately 5 (rats) and 11 (rabbits) times the exposure at the maximum recommended human dose (MRHD).
No adverse developmental effects were observed after oral administration of ivacaftor to pregnant rats from organogenesis through lactation at doses that produced maternal exposures approximately 3 times the exposures at the MRHD, respectively ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and miscarriage is 15% to 20% in clinically recognized pregnancies.
Data Animal Data In an embryo-fetal development study, pregnant rats were administered ivacaftor at oral doses of 50, 100, or 200 mg/kg/day during the period of organogenesis from gestation days 7-17. Ivacaftor did not affect fetal survival at exposures up to 5 times the MRHD (based on summed AUCs for ivacaftor and its metabolites at maternal oral doses up to 200 mg/kg/day). Maternal toxicity was observed at 100 and 200 mg/kg/day (3 and 5 times the exposure at the MRHD) and was associated with a decrease in fetal body weights at a maternal dose of 200 mg/kg/day (5 times the MRHD).
In an EFD study, pregnant rabbits were administered ivacaftor at oral doses of 25, 50, or 100 mg/kg/day during the period of organogenesis from gestation days 7-19. Ivacaftor did not affect fetal development or survival at exposures up to 11 times the MRHD (on an ivacaftor AUC basis at maternal oral doses up to 100 mg/kg/day). Maternal toxicity (i.e., death, decreased food consumption, decreased mean body weight and body weight gain, decreased clinical condition, abortions) was observed at doses greater than or equal to 50 mg/kg/day (approximately 5 times the MRHD).
In a pre- and post-natal development study, pregnant female rats were administered ivacaftor at oral doses of 50, 100, or 200 mg/kg/day from gestation day 7 through lactation day 20. Ivacaftor had no effects on delivery or growth and development of offspring at exposures up to 3 times the MRHD (based on summed AUCs for ivacaftor and its metabolites at maternal oral doses up to 100 mg/kg/day). Decreased fetal body…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
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