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KALYDECO™ (ivacaftor) Tablets
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HIGHLIGHTS OF PRESCRIBING INFORMATION |
These highlights do not include all the information needed to use KALYDECO safely and effectively. See full prescribing information for KALYDECO.
KALYDECO™ (ivacaftor) Tablets
Initial U.S. Approval: 2012
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INDICATIONS AND USAGE
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KALYDECO is classified as a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator. KALYDECO is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who have a G551D mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the G551D mutation. (1)
Limitations of Use:
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Not effective in patients with CF who are homozygous for the F508del mutation in the CFTR gene. (1, 14)
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KALYDECO has not been studied in other populations of patients with CF. (1, 14)
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DOSAGE AND ADMINISTRATION
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Adults and pediatric patients age 6 years and older: one 150 mg tablet taken orally every 12 hours with fat-containing food. (2, 12.3)
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Reduce dose in patients with moderate and severe hepatic impairment. (8.6, 12.3)
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Reduce dose when co-administered with drugs that are moderate or strong CYP3A inhibitors. (7.1, 12.3)
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DOSAGE FORMS AND STRENGTHS
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CONTRAINDICATIONS
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WARNINGS AND PRECAUTIONS
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Elevated transaminases (ALT or AST): Transaminases (ALT and AST) should 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. (5.1, 6)
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Use with CYP3A inducers: Concomitant use with strong CYP3A inducers (e.g., rifampin, St. John's Wort) substantially decreases exposure of ivacaftor which may diminish effectiveness. Therefore, co-administration is not recommended. (5.2, 7.2, 12.3)
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ADVERSE REACTIONS
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The most common adverse drug reactions to KALYDECO (occurring ≥8% of patients with CF who have a G551D mutation in the CFTR gene) were headache, oropharyngeal pain, upper respiratory tract infection, nasal congestion, abdominal pain, nasopharyngitis, diarrhea, rash, nausea, and dizziness. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Vertex Pharmaceuticals Incorporated at 1-877-752-5933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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DRUG INTERACTIONS
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CYP3A inhibitors: Reduce KALYDECO dose to 150 mg twice-a-week when co-administered with strong CYP3A inhibitors (e.g., ketoconazole). Reduce KALYDECO dose to 150 mg once daily when co-administered with moderate CYP3A inhibitors (e.g., fluconazole). Avoid food containing grapefruit or Seville oranges. (7.1, 12.3)
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See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling |
Revised: 01/2012 |
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FULL PRESCRIBING INFORMATION: CONTENTS* |
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FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
KALYDECO is classified as a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator. KALYDECO is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who have a G551D mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the G551D mutation.
Limitations of Use
KALYDECO is not effective in patients with CF who are homozygous for the F508del mutation in the CFTR gene and has not been studied in other populations of patients with CF.
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Information in Adults and Children Ages 6 Years and Older
The recommended dose of KALYDECO for both adults and pediatric patients age 6 years and older is one 150 mg tablet taken orally every 12 hours (300 mg total daily dose) with fat-containing food. Examples of appropriate fat-containing food include eggs, butter, peanut butter, cheese pizza, etc. [see Clinical Pharmacology (12.3) and Patient Counseling Information (17.4)].
2.3 Dosage Adjustment for Patients Taking Drugs that are CYP3A Inhibitors
When KALYDECO is being co-administered with strong CYP3A inhibitors (e.g., ketoconazole) the dose should be reduced to 150 mg twice-a-week. The dose of KALYDECO should be reduced to 150 mg once daily when co-administered with moderate CYP3A inhibitors (e.g., fluconazole). Food containing grapefruit or Seville oranges should be avoided [see Drug Interactions (7.1), Clinical Pharmacology (12.3), and Patient Counseling Information (17.2)].
3 DOSAGE FORMS AND STRENGTHS
150 mg tablets.
4 CONTRAINDICATIONS
None known.
5 WARNINGS AND PRECAUTIONS
5.1 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 (6)].
5.2 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 (7.2) and Clinical Pharmacology (12.3)].
6 ADVERSE REACTIONS
The following adverse reaction is discussed in greater detail in other sections of the label:
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The overall safety profile of KALYDECO is based on pooled data from placebo-controlled clinical trials conducted in 353 patients with CF who had a G551D mutation in the CFTR gene or were homozygous for the F508del mutation. Of the 353 patients, 50% of patients were female and 97% were Caucasian; 221 received KALYDECO and 132 received placebo from 16 to 48 weeks. Patients treated with KALYDECO were between the ages of 6 and 53 years.
In these trials, the proportion of patients who prematurely discontinued study drug due to adverse reactions was 2% for KALYDECO-treated patients and 5% for placebo-treated patients. Serious adverse reactions, whether considered drug-related or not by the investigators, which occurred more frequently in KALYDECO-treated patients included abdominal pain, increased hepatic enzymes, and hypoglycemia.
Overall, the most common adverse reactions in 353 patients with CF were headache (17%), upper respiratory tract infection (16%), nasal congestion (16%), nausea (10%), rash (10%), rhinitis (6%), dizziness (5%), arthralgia (5%), and bacteria in sputum (5%).
The incidence of adverse reactions below is based upon two double-blind, placebo-controlled 48-week clinical trials in a total of 213 patients with CF ages 6 to 53 who have a G551D mutation in the CFTR gene and who were treated with KALYDECO 150 mg orally or placebo twice daily. Table 1 shows adverse reactions occurring in ≥8% of KALYDECO-treated patients with CF who have a G551D mutation in the CFTR gene that also occurred at a higher rate than in the placebo-treated patients in the two double-blind, placebo-controlled trials.
Table 1: Incidence of Adverse Drug Reactions in ≥8% of KALYDECO-Treated Patients with a G551D Mutation in the CFTR Gene and Greater than Placebo in 2 Placebo-Controlled Phase 3 Clinical Trials of 48 Weeks Duration
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Incidence: Pooled 48-week Trials |
Adverse Reaction
(Preferred Term) |
KALYDECO
N=109
n (%) |
Placebo
N=104
n (%) |
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Headache
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| 以下是“全球医药”详细资料 |
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