ivacaftor (Rx)

  • Print
Brand and Other Names:Kalydeco

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 150mg

oral granules

  • 50mg/unit dose packet
  • 75mg/unit dose packet
more...

Cystic Fibrosis

Indicated for the treatment of cystic fibrosis in adults and children ≥2 years who have R117H, G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R mutations in the CFTR gene; not effective if homozygous for the F508del mutation in the CFTR gene

150 mg PO q12hr with fat-containing food

Dosage Modification

Coadministration with strong CYP3A inhibitors: Reduce dose to 150 mg PO twice-a-week

Coadministration with moderate CYP3A inhibitors: Reduce dose to 150 mg PO qDay

Renal & Hepatic Impairment

Renal impairment

  • Has not been studied in patients with renal impairment
  • Mild-to-moderate: No dosage adjustment required
  • Severe (CrCl <30 mL/min) or end stage renal disease: Caution advised

Hepatic impairment

  • Mild (Child-Pugh Class A): No dosage adjustment required
  • Moderate (Child-Pugh Class B): Reduce dose to 150 mg PO qDay
  • Severe (Child-Pugh Class C): Has not been studied, but exposure is expected to be higher; use with caution at reduced dose of 150 mg PO qDay or less frequently

Dosing Considerations

Not effective in patients with CF who are homozygous for the F508del mutation in the CFTR gene

Dosage Forms & Strengths

tablet

  • 150mg

oral granules

  • 50mg/unit dose packet
  • 75mg/unit dose packet
more...

Cystic Fibrosis

Indicated for the treatment of cystic fibrosis in adults and children ≥2 years who have R117H, G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R mutations in the CFTR gene; not effective if homozygous for the F508del mutation in the CFTR gene

<2 years: Safety and efficacy not established

2-5 years, <14 kg: 50 mg granules PO q12hr

2-5 years, ≥14 kg: 75 mg granules PO q12hr

6-17 years: 150 mg PO q12hr

Take just before or after eating fat-containing food

Dosage Modification

Coadministration with strong CYP3A inhibitors: Reduce dose to 150 mg PO twice-a-week

Coadministration with moderate CYP3A inhibitors: Reduce dose to 150 mg PO qDay

Renal & Hepatic Impairment

Renal impairment

  • Has not been studied in patients with renal impairment
  • Mild-to-moderate: No dosage adjustment required
  • Severe (CrCl <30 mL/min) or end stage renal disease: Caution advised

Hepatic impairment

  • Mild (Child-Pugh Class A): No dosage adjustment required
  • Moderate (Child-Pugh Class B): Reduce dose to 150 mg PO qDay
  • Severe (Child-Pugh Class C): Has not been studied, but exposure is expected to be higher; use with caution at reduced dose of 150 mg PO qDay or less frequently

Dosing Considerations

Not effective in patients with CF who are homozygous for the F508del mutation in the CFTR gene

Next:

Interactions

Interaction Checker

and ivacaftor

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Headache (24%)

            Oropharyngeal pain (22%)

            Upper respiratory tract injection (22%)

            Nasal congestion (20%)

            Abdominal pain (16%)

            Nasopharyngitis (15%)

            Rash (13%)

            Diarrhea (13%)

            Nausea (12%)

            1-10%

            Dizziness (9%)

            Rhinitis (6%)

            Arthralgia (5%)

            Bacteria in sputum (5%)

            Previous
            Next:

            Warnings

            Contraindications

            None

            Cautions

            Elevated transaminases (ALT or AST); evaluate liver enzymes before initiating and every 3 months for the first year of treatment, and then annually thereafter; consider more frequent monitoring for patients with a history of transaminase elevations; interrupt dose if ALT or AST increases to >5 times ULN

            Coadministration with CYP3A inhibitors require dose reduction (see Dosage Modification)

            Avoid eating grapefruit juice, grapefruit, or Seville oranges during treatment with ivacaftor; these fruits contain 1 or more components that moderately inhibit CYP3A

            Avoid coadministration with strong CYP3A inducers (eg, rifampin); systemic exposure of ivacaftor substantially decreased (~9-fold), which may reduce therapeutic effect

            Ivacaftor and its M1 metabolite may inhibit CYP3A and P-gp; caution when coadministration with CYP3A and/or P-gp substrates

            Cases of noncongenital lens opacities/cataracts have been reported in pediatric patients up to age 12 yr; although other risk factors were present in some cases (eg, corticosteroid use and/or exposure to radiation), a possible risk attributable to ivacaftor cannot be excluded; cataracts were seen in juvenile rats dosed with ivacaftor at dose levels of 10 mg/kg/day; baseline and follow-up ophthalmological examinations are recommended in pediatric patients

            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy Category: B

            Lactation: Probably excreted in human breast milk (based on studies in rats); caution advised

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Potentiates the cystic fibrosis transmembrane conductance regulator (CFTR)

            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 G551D-CFTR protein

            In addition to G551D-CFTR, ivacaftor potentiated gating of other mutant CFTR genes (ie, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R); it also potentiated channel-opening of R117H-CFTR, which has low gating and reduced channel amplitude compared to normal CFTR

            Absorption

            Peak Plasma Time: 4 hr (with high fat food)

            Peak Plasma Concentration: 768 ng/mL

            AUC: 10,600 ng•hr/mL

            Distribution

            Protein Bound: 99% (primarily albumin and alpha 1-acid glycoprotein)

            Does not bind to red blood cells Vd: 353 L

            Metabolism

            Metabolized by CYP3A

            Metabolites: M1 and M6 are the 2 major metabolites; M1 has 1/6 the potency of ivacaftor and is considered pharmacologically active; whereas, M6 has <1/50 the potency of ivacaftor and is not considered pharmacologically active

            Ivacaftor and its M1 metabolite may inhibit CYP3A and P-gp

            Elimination

            Half-life: 12 hr

            Total body clearance: 17.3 L/hr

            Excretion: feces 87.8% (M1 and M6 accounted for approximately 65% of the total dose eliminated with 22% as M1 and 43% as M6); urine (negligible)

            Pharmacogenomics

            G551D mutation in the CFTR gene

            • In 2 studies of patients with the G551D mutation, treatment with ivacaftor resulted in a significant improvement in FEV1
            • The treatment difference between ivacaftor and placebo for the mean absolute change in percent predicted FEV1 from baseline through Week 24 was 10.6 percentage points (P < 0.0001) in Trial 1 and 12.5 percentage points (P < 0.0001) in Trial 2
            • These changes persisted through 48 weeks

            Homozygous for the F508del mutation in the CFTR gene

            • Should not be used in patients 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 ivacaftor treatment compared to placebo
            Previous
            Next:

            Administration

            Oral Tablets

            Take with fat-containing food (eg, eggs, butter, peanut butter, cheese pizza)

            Oral Granules

            The entire contents of each packet of oral granules should be mixed with 1 teaspoon (5 mL) of age-appropriate soft food or liquid and completely consumed

            Food or liquid should be at or below room temperature

            Once mixed, the product has been shown to be stable for 1 hour, and therefore should be consumed during this period

            Some examples of soft foods or liquids may include puréed fruits or vegetables, yogurt, applesauce, water, milk, or juice

            Each dose should be administered just before or just after eating fat-containing food (eg, eggs, butter, peanut butter, cheese pizza)

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous