Ivacaftor

What is Ivacaftor?

• Ivacaftor (KALYDECO) is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator used to treat patients with cystic fibrosis with specific mutations of the CFTR.

What are the uses of this medicine?

• This medicine is used for the treatment of cystic fibrosis (CF) in patients age 4 months and older who have at least one mutation in their CF gene that is responsive to KALYDECO.

How does this medicine work?

• 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 CFTR protein located at the cell surface.
• The overall level of ivacaftor-mediated CFTR chloride transport is dependent on the amount of CFTR protein at the cell surface and how responsive a particular mutant CFTR protein is to ivacaftor potentiation.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who use certain medicines or herbal supplements such as:

• the antibiotics rifampin (RIFAMATE®, RIFATER®) or rifabutin (MYCOBUTIN®)
• seizure medications such as phenobarbital, carbamazepine (TEGRETOL®, CARBATROL®, EQUETRO®) or phenytoin (DILANTIN®, PHENYTEK®)
• St. John's wort

What drug interactions can this medicine cause?

• Co-administration with fluconazole, a moderate inhibitor of CYP3A, increased ivacaftor exposure by 3-fold. Therefore, a reduction of the KALYDECO dose is recommended for patients taking concomitant moderate CYP3A inhibitors, such as fluconazole and erythromycin.
• Avoid food containing grapefruit during treatment with KALYDECO.
• Co-administration with ketoconazole, a strong CYP3A inhibitor, significantly increased ivacaftor exposure [measured as area under the curve (AUC)] by 8.5-fold.
• Co-administration with strong CYP3A inducers, such as rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John's wort is not recommended.
• Caution and appropriate monitoring are recommended when co-administering KALYDECO with sensitive CYP3A and/or P-gp substrates, such as digoxin, cyclosporine, and tacrolimus.

Is this medicine FDA approved?

• Initial U.S. Approval: 2012

How should this medicine be used?

• Verify pregnancy status of females of reproductive potential within 7 days prior to initiating ERIVEDGE.

Recommended dosage:

• Adults and pediatric patients age 6 years and older: one 150 mg tablet taken orally every 12 hours with fat-containing food.
• Pediatric patients 4 months to less than 6 months of age and 5 kg or greater: one 25 mg packet mixed with 1 teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food.
• Pediatric patients 6 months to less than 6 years of age and weighing 5 kg to less than 7 kg: one 25 mg packet mixed with 1 teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food.
• Pediatric patients 6 months to less than 6 years of age and weighing 7 kg to less than 14 kg: one 50 mg packet mixed with 1 teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food.
• Pediatric patients 6 months to less than 6 years of age and 14 kg or greater: one 75 mg packet mixed with 1 teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food.
• Reduce dose in patients 6 months and older with moderate or severe hepatic impairment.

Administration:

• Take KALYDECO exactly as your doctor tells you to take it.
• Take your doses of KALYDECO 12 hours apart.
• If you miss a dose of KALYDECO and it is within 6 hours of when you usually take it, take your dose of KALYDECO as prescribed with fat-containing food as soon as possible.
• If you miss a dose of KALYDECO and it is more than 6 hours after the time you usually take it, skip that dose only and take the next dose when you usually take it. Do not take 2 doses at the same time to make up for your missed dose.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 150 mg
• Oral granules: Unit-dose packets of 25 mg, 50 mg and 75 mg

This medicine is available in fallowing brand namesː

• KALYDECO

What side effects can this medication cause?

The most common side effects of this medicine include:

• headache

upper respiratory tract infection (common cold), including:

• sore throat
• nasal or sinus congestion
• runny nose
• stomach (abdominal) pain
• diarrhea
• rash
• nausea
• dizziness

KALYDECO can cause serious side effects:

• High liver enzymes in the blood have been reported in patients receiving KALYDECO
• Abnormality of the eye lens (cataract)

What special precautions should I follow?

• Elevated transaminases have been reported in patients with CF receiving KALYDECO. Transaminases (ALT and AST) should be assessed prior to initiating KALYDECO, every 3 months during the first year of treatment, and annually thereafter. In patients with a history of transaminase elevations, more frequent monitoring of liver function tests should be considered. Patients who develop increased transaminase levels should be closely monitored until the abnormalities resolve. Interrupt dosing 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.
• 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.
• Non-congenital lens opacities/cataracts have been reported in pediatric patients treated with KALYDECO. Baseline and follow-up examinations are recommended in pediatric patients initiating KALYDECO treatment.

What to do in case of emergency/overdose?

• There have been no reports of overdose with KALYDECO.

Management of overdosage:

• No specific antidote is available for overdose with KALYDECO.
• Treatment of overdose with KALYDECO consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.

Can this medicine be used in pregnancy?

• There are limited and incomplete human data from clinical trials and post marketing reports on use of KALYDECO in pregnant women.

Can this medicine be used in children?

• The safety and effectiveness of KALYDECO for the treatment of CF have been established in pediatric patients 4 months to 17 years of age who have one mutation in the CFTR gene.
• The safety and effectiveness of KALYDECO in patients with CF younger than 4 months of age have not been established. The use of KALYDECO in children under the age of 4 months is not recommended.
• Not recommended in patients 4 months to less than 6 months of age with hepatic impairment.

What are the active and inactive ingredients in this medicine?

• Active ingredient: ivacaftor

• Inactive ingredients:
• KALYDECO Tablets are light blue, film-coated, capsule-shaped tablets for oral administration and contain the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose acetate succinate, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate.

• The tablet film coat contains: carnauba wax, FD&C Blue #2, PEG 3350, polyvinyl alcohol, talc, and titanium dioxide.
• The printing ink contains: ammonium hydroxide, iron oxide black, propylene glycol, and shellac.
• KALYDECO Oral Granules are white to off-white granules for oral administration (sweetened but unflavored) and contain the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose acetate succinate, lactose monohydrate, magnesium stearate, mannitol, sucralose, and sodium lauryl sulfate.

Who manufactures and distributes this medicine?

• Manufactured for:

Vertex Pharmaceuticals Incorporated 50 Northern Avenue Boston, MA

What should I know about storage and disposal of this medication?

• Store KALYDECO at room temperature between 68°F to 77°F (20°C to 25°C).
• Do not use KALYDECO after the expiration date on the package.
• Keep KALYDECO and all medicines out of the reach of children.

• Dailymed label info on Ivacaftor
• FDA Ivacaftor

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