Drug Interaction:
CYP3A inhibitors:
Reduce KALYDECO dose to 150 mg twice a week
when co-administered with strong CYP3A inhibitors (e.g., ketoconazole).
Reduce Limitations of Use: KALYDECO dose to 150 mg once daily when
co-administered with moderate
Not effective in patients with CF who are homozygous for the F508del
CYP3A inhibitors (e.g., fluconazole). Avoid food containing grapefruit
or mutation in the CFTR gene. (1, 14) Seville oranges.
Indication:
KALYDECO® (ivacaftor) Tablets, for oral
Initial U.S. Approval: 2012
Drug Name- Kalydeco
Active Ingredient - Ivacaftor
For treatment of rare form of cystic fibrosis(CF) in patients ages 6 years and
older who have specific G551D mutation in the Cystic Fibrosis Transmembrane
Regulator(CFTR)
Indication-
For treatment of rare form of cystic fibrosis(CF) in patients ages 6 years and
older who have specific G551D mutation in the Cystic Fibrosis Transmembrane
Regulator(CFTR)
Approved by FDA on 31-1-2012 (Ref- FDA Approved List- 2012)
Adverse Reaction:
The most common adverse drug reactions(8%) are-
headache, oropharyngeal pain, upper respiratory tract infection, nasal
congestion, abdominal pain, nasopharyngitis, diarrhea, rash, nausea, and
dizziness
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
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.
-
Dosages/ Overdosage Etc:
Indication-
For treatment of rare form of cystic fibrosis(CF) in patients ages 6 years and
older who have specific G551D mutation in the Cystic Fibrosis Transmembrane
Regulator(CFTR)
INDICATIONS AND USAGE-
KALYDECO is a cystic fibrosis transmembrane conductance regulator inducers
(e.g., rifampin, St. John’s Wort) substantially decreases (CFTR) potentiator indicated
for the treatment of cystic fibrosis (CF) in exposure of ivacaftor, which may diminish
effectiveness. Therefore, patients age 6 years and older who have one of the
following mutations in the co-administration is not recommended.
DOSAGE AND ADMINISTRATION
Adults and pediatric patients age 6 years and older: one 150 mg tablet
Reduce dose in patients with moderate and severe hepatic impairment.
Reduce dose when co-administered with drugs that are moderate or strong
CYP3A inhibitors.
DOSAGE FORMS AND STRENGTHS
Tablets: 150 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling
1. 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
2. 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
3. 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)
4. Take with Fat-Containing Food
Inform 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.
5. Cataracts
Inform patients that abnormality of the eye lens (cataract) has been noted
in some children up to 12 years of age receiving KALYDECO. Baseline and
follow-up ophthalmological examinations should be performed in pediatric
patients initiating KALYDECO treatment
Pharmacology/ Pharmacokinetics:
1. Mechanism of Action
Ivacaftor is a potentiator of the CFTR protein. The CFTR protein is a chloride channel
present at the surface of epithelial cells in multiple organs. Ivacaftor facilitates increased
chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein.
2. Pharmacokinetics
The pharmacokinetics of ivacaftor is similar between healthy adult volunteers and patients
with CF.After oral administration of a single 150 mg dose to healthy volunteers
in a fed state, peak plasma concentrations (Tmax) occurred at approximately 4 hours,
and the mean (±SD) for AUC and Cmax were 10600 (5260) ng*hr/mL and 768 (233) ng/mL,
respectively.
After every 12-hour dosing, steady-state plasma concentrations of ivacaftor were
reached by days 3 to 5, with an accumulation ratio ranging from 2.2 to 2.9.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1.Pregnancy Teratogenic effects:
Pregnancy Category B.
There are no adequate and well-controlled studies of KALYDECO in pregnant women.
Because animal reproduction studies are not always predictive of human response,
KALYDECO should be used during pregnancy only if clearly needed.
2. Nursing Mothers
Ivacaftor is excreted into the milk of lactating female rats. Excretion of ivacaftor
into human milk is probable. Caution should be exercised when KALYDECO
is administered to a nursing woman.
3. Pediatric Use
The safety and efficacy of KALYDECO in patients with CF younger than age 6 years
have not been established.
4. 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.
Manufacturer Details