Kalydeco(ivacaftor)的使用方法,剂量调整及注意事项？

The recommended dose of (ivacaftor) for adults and children aged 6 years and above is 150 mg, taken orally every 12 hours. Patients with liver damage and when combined with CYP3A inhibitor drugs need to adjust the dose. When using the drug, attention should also be paid to elevated transaminases (ALT or AST), hypersensitivity reactions, including immediate allergic reactions, combined use with CYP3A inducers, and cataracts.

About Kalydeco(ivacaftor)

On January 31, 2012, Vertex Pharmaceuticals' Ivacaftor (trade name: Kalydeco) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of cystic fibrosis (CF) patients over 6 years old caused by a specific G551D mutation in the CFTR gene. Ivacaftor is a potentiator of CFTR protein, which enhances the transmembrane transport ability of chloride ions across the cell membrane by increasing ion flow.

How to use Kalydeco(ivacaftor)

1. Dosage

(1) Recommended dosage for adults and pediatric patients 6 years of age and older

KALYDECO is a medicine used to treat cystic fibrosis (CF). It is suitable for adults and pediatric patients 6 years and older. Doses of 150 mg taken orally every 12 hours are recommended, for a total daily dose of 300 mg. To maximize the effect of the drug, it is recommended to consume fatty foods while taking KALYDECO. This is because fat helps the body absorb medications, thereby increasing their bioavailability and efficacy.

(2) Recommended dosage for pediatric patients from 1 month to < 6 years old

The recommended dosage of KALYDECO (granules) for pediatric patients 1 month to less than 6 years of age is based on body weight and is shown in Table 1. Take KALYDECO with fatty foods.

Table 1: Recommended doses of KALYDECO Oral Granules by body weight in pediatric patients 1 month to less than 6 years of age

2. Usage

(1) Take KALYDECO tablets or oral granules with fatty foods. Examples include eggs, butter, peanut butter, cheese pizza, whole milk dairy products (such as whole milk, cheese, yogurt, breast milk or infant formula), etc.

(2) Tablet administration instructions: Swallow the tablet whole.

(3) Oral Granule Dosing Instructions: Give each dose of KALYDECO Oral Granules immediately before and after ingestion of fatty foods. Mix the entire contents of each package of oral granules with one teaspoon (5 mL) of age-appropriate soft food or liquid (at or below room temperature). Some examples of soft foods or liquids might include plain fruits or vegetables, yogurt, applesauce, water, breast milk, infant formula, milk, or juice. Food or liquids should be at or below room temperature. Once mixed, this product should be completely consumed within 1 hour.

Dosage adjustment of Kalydeco(ivacaftor)

1. Recommended dosage for patients with liver damage

KALYDECO is not recommended for patients under 6 months of age with any degree of hepatic impairment. For patients 6 months and older with hepatic impairment, the recommended dosage of KALYDECO taken with fatty foods is as follows:

(1) Mild liver damage (Child-Pugh class A)

①Less than 6 months: KALYDECO is not recommended.

②No dose adjustment is required for patients 6 months or older.

(2) Moderate liver damage (Child-Pugh class B)

①Less than 6 months: KALYDECO is not recommended.

② 6 months to less than 6 years old: 1 packet (containing 25 mg, 50 mg or 75 mg ivacaftor) oral granules, once daily, based on the recommended dosage for age and weight in Table 1.

③6 years and above: 150 mg orally, once a day.

(3) Severe liver damage (Child-Pugh grade C)

Not to be used in patients under 6 months of age. Patients 6 months of age and older should use 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, reduced doses should be used with caution in patients 6 months or older with severe hepatic impairment after weighing the risks and benefits of treatment.

①Less than 6 months: KALYDECO is not recommended.

② 6 months to less than 6 years: 1 packet (containing 25 mg, 50 mg, or 75 mg ivacaftor) oral granules, once daily or less frequently as recommended for age and weight in Table 1.

③6 years and above: 150 mg orally, once a day or less frequently.

2. Dose adjustment for patients taking CYP3A inhibitor drugs

Concomitant use of moderate or strong CYP3A inhibitors is not recommended in patients younger than 6 months of age. Foods or drinks containing grapefruit should be avoided.

Dose adjustment in patients 6 months and older taking CYP3A inhibitors:

(1) Moderate CYP3A inhibitor

①Less than 6 months: KALYDECO is not recommended.

② 6 months to less than 6 years old: 1 packet (containing 25 mg, 50 mg or 75 mg ivacaftor) oral granules, once daily, based on the recommended dosage for age and weight in Table 1.

③6 years and above: 150 mg orally, once a day.

(2) Strong CYP3A inhibitor

①Less than 6 months: KALYDECO is not recommended.

② 6 months to under 6 years old: According to the recommended dosage for age and weight in Table 1, give 1 packet (containing 25 mg, 50 mg or 75 mg ivacaftor) of oral granules twice a week.

③6 years and above: 150 mg orally, twice a week.

Kalydeco(ivacaftor)

1. Elevated transaminase (ALT or AST)

Elevated transaminases have been reported in patients with CF receiving KALYDECO. ALT and AST should be assessed prior to initiating KALYDECO, 3 months each for the first year of treatment, and annually thereafter. Increased frequency of liver function test monitoring should be considered in patients with a history of elevated transaminases. Patients with elevated transaminase levels should be monitored closely until the abnormality resolves. Dosing should be interrupted in patients with ALT or AST greater than 5 times the upper limit of normal (ULN).

2. Hypersensitivity reactions, including immediate anaphylaxis

Hypersensitivity reactions, including cases of anaphylaxis, have been reported postmarketing. If signs or symptoms of serious hypersensitivity reaction occur during treatment, discontinue KALYDECO and initiate appropriate treatment.

3. Use in combination with CYP3A inducers

Coadministration of KALYDECO with strong CYP3A inducers, such as rifampicin, significantly reduces ivacaftor exposure, which may reduce the therapeutic effectiveness of KALYDECO. Therefore, coadministration of KALYDECO with strong CYP3A inducers (e.g., rifampicin, St. John's wort) is not recommended.

4. Cataract

Cases of non-congenital lens opacities/cataracts have been reported in pediatric patients treated with KALYDECO. Although other risk factors exist in some cases (such as corticosteroid use and/or exposure to radiation), the possible risks attributable to KALYDECO cannot be excluded. Baseline and follow-up ophthalmic examinations are recommended for pediatric patients initiating treatment with KALYDECO.

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