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Kalydeco

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Kalydeco

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Transaminase (ALT or AST) Elevations

Elevated transaminases have been reported in patients with CF receiving KALYDECO. It is recommended that ALT and AST be assessed prior to initiating KALYDECO, every 3 months during the first year of treatment, and annually thereafter. Patients who develop increased transaminase levels should be closely monitored until the abnormalities resolve. Dosing should be interrupted in patients with ALT or AST of greater than 5 times the upper limit of normal (ULN). Following resolution of transaminase elevations, consider the benefits and risks of resuming KALYDECO dosing [see ADVERSE REACTIONS].

Concomitant Use With CYP3A Inducers

Use of KALYDECO with strong CYP3A inducers, such as rifampin, substantially decreases the exposure of ivacaftor, which may reduce the therapeutic effectiveness of KALYDECO. Therefore, co-administration of KALYDECO with strong CYP3A inducers (e.g., rifampin, St. John's Wort) is not recommended [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).

Transaminase (ALT Or AST) Elevations And Monitoring

Inform patients that elevation in liver tests have occurred in patients treated with KALYDECO. Liver function tests will be performed prior to initiating KALYDECO, every 3 months during the first year of treatment and annually thereafter [see WARNINGS AND PRECAUTIONS].

Drug Interactions With CYP3A Inducers And Inhibitors

Ask patients to tell you all the medications they are taking including any herbal supplements or vitamins. Co-administration of KALYDECO with strong CYP3A inducers (e.g., rifampin, St. John's Wort) is not recommended as they may reduce the therapeutic effectiveness of KALYDECO. Reduction of the dose of KALYDECO to 150 mg twice a week is recommended when co-administered with strong CYP3A inhibitors, such as ketoconazole. Dose reduction to 150 mg once daily is recommended when co-administered with moderate CYP3A inhibitors, such as fluconazole. Food containing grapefruit or Seville oranges should be avoided [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

Use In Patients With Hepatic Impairment

Inquire and/or assess whether patients have liver impairment. Reduce the dose of KALYDECO in patients with moderately impaired hepatic function (Child-Pugh Class B, score 7 to 9) to 150 mg once daily. KALYDECO has not been studied in patients with severe hepatic impairment (Child-Pugh Class C, score 10-15); however, exposure is expected to be substantially higher than that observed in patients with moderate hepatic impairment. When benefits are expected to outweigh the risks, KALYDECO should be used with caution in patients with severe hepatic impairment at a dose of 150 mg given once daily or less frequently. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh Class A, score 5-6) [see CLINICAL PHARMACOLOGY].

Take With Fat-Containing Food

Inform your patients that KALYDECO is best absorbed by the body when taken with food that contains fat. A typical CF diet will satisfy this requirement. Examples include eggs, butter, peanut butter, cheese pizza, etc.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Two-year studies were conducted in mice and rats to assess carcinogenic potential of KALYDECO. No evidence of tumorigenicity was observed in mice or rats at ivacaftor oral doses up to 200 mg/kg/day and 50 mg/kg/day, respectively (approximately equivalent to and 3 to 5 times the MRHD, respectively, based on summed AUCs of ivacaftor and its metabolites).

Ivacaftor was negative for genotoxicity in the following assays: Ames test for bacterial gene mutation, in vitro chromosomal aberration assay in Chinese hamster ovary cells, and in vivo mouse micronucleus test.

Ivacaftor impaired fertility and reproductive performance indices in male and female rats at 200 mg/kg/day (approximately 5 and 6 times, respectively, the MRHD based on summed AUCs of ivacaftor and its metabolites). Increases in prolonged diestrus were observed in females at 200 mg/kg/day. Ivacaftor also increased the number of females with all nonviable embryos and decreased corpora lutea, implantations, and viable embryos in rats at 200 mg/kg/day (approximately 6 times the MRHD based on summed AUCs of ivacaftor and its metabolites) when dams were dosed prior to and during early pregnancy. These impairments of fertility and reproductive performance in male and female rats at 200 mg/kg/day were attributed to severe toxicity. No effects on male or female fertility and reproductive performance indices were observed at &e;100 mg/kg/day (approximately 3 times the MRHD based on summed AUCs of ivacaftor and its metabolites).

Use In Specific Populations

Pregnancy

Teratogenic effects

Pregnancy Category B. There are no adequate and well-controlled studies of KALYDECO in pregnant women. Ivacaftor was not teratogenic in rats at approximately 6 times the maximum recommended human dose (MRHD) (based on summed AUCs for ivacaftor and its metabolites at a maternal dose of 200 mg/kg/day). Ivacaftor was not teratogenic in rabbits at approximately 12 times the MRHD (on an ivacaftor AUC basis at a maternal dose of 100 mg/kg/day, respectively). Placental transfer of ivacaftor was observed in pregnant rats and rabbits. Because animal reproduction studies are not always predictive of human response, KALYDECO should be used during pregnancy only if clearly needed.

Nursing Mothers

Ivacaftor is excreted into the milk of lactating female rats. Excretion of ivacaftor into human milk is probable. There are no human studies that have investigated the effects of ivacaftor on breast-fed infants. Caution should be exercised when KALYDECO is administered to a nursing woman.

Pediatric Use

The safety and efficacy of KALYDECO in patients 6 to 17 years of age with CF who have a G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R mutation in the CFTR gene has been demonstrated [see ADVERSE REACTIONS and Clinical Studies].

The safety and efficacy of KALYDECO in patients with CF younger than age 6 years have not been established.

Geriatric Use

CF is largely a disease of children and young adults. Clinical trials of KALYDECO did not include sufficient numbers of patients 65 years of age and over to determine whether they respond differently from younger patients.

Hepatic Impairment

No dose adjustment is necessary for patients with mild hepatic impairment (Child-Pugh Class A). A reduced dose of 150 mg once daily is recommended in patients with moderate hepatic impairment (Child-Pugh Class B). Studies have not been conducted 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 dose of 150 mg once daily or less frequently in patients with severe hepatic impairment after weighing the risks and benefits of treatment [see Pharmacokinetics].

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 dose 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.

Patients With CF Who Are Homozygous For The F508del Mutation In The CFTR Gene

Efficacy results from a double-blind, placebo-controlled trial in patients with CF who are homozygous for the F508del mutation in the CFTR gene showed no statistically significant difference in forced expiratory volume exhaled in one second (FEV1) over 16 weeks of KALYDECO treatment compared to placebo [see Clinical Studies]. Therefore, KALYDECO should not be used in patients homozygous for the F508del mutation in the CFTR gene.

Last reviewed on RxList: 7/15/2014
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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