• Cystic fibrosis in patients with one mutation in the CFTR gene that is responsive to ivacaftor potentiation based on clinical and/or in vitro assay data.

Contraindicated in:

• Concurrent use of strong CYP3A inducers
• Pedi: Children <6 mo with hepatic impairment or receiving moderate or strong CYP3A inhibitors.

Use Cautiously in:

• Moderate to severe hepatic impairment (dose ↓ recommended)
• Concurrent use of CYP3A inhibitors (dose ↓ recommended)
• Concurrent use of CYP3A and/or P-glycoprotein substrates
• Severe renal impairment (CCr <30 mL/min) or end stage renal disease
• OB: Safety not established in pregnancy
• Lactation: Safety not established in breastfeeding
• Pedi: Children <4 mo (safety and effectiveness not established).

CNS: headache, dizziness.

Derm: rash.

EENT: nasal congestion, lens opacities/cataracts, oropharyngeal pain.

Endo: hyperglycemia, hypoglycemia.

GI: nausea, abdominal pain, diarrhea, ↑ liver enzymes.

MS: arthralgia, musculoskeletal chest pain, myalgia.

Drug-Drug:

• Strong CYP3A inducers including rifampin, rifabutin, phenobarbital, carbamazepine and phenytoin↓ levels and effectiveness; avoid concurrent use
• Strong CYP3A inhibitors including ketoconazole, itraconazole, posaconazole, voriconazole, and clarithromycin may ↑ levels and risk of adverse reactions (dose ↓ recommended).
• Moderate CYP3A inhibitors including fluconazole or erythromycin may ↑ levels and risk of adverse reactions (dose ↓ recommended).
• May ↑ levels and effects of CYP3A substrates including alprazolam, diazepam, midazolam and triazolam.
• May ↑ levels and effects of P-glycoprotein substrates including digoxin, cyclosporine and tacrolimus.
• May alter the effects of warfarin.

Drug-Natural Products:

• St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

• Grapefruit or Seville oranges may ↑ levels and ↑ risk of toxicity; avoid concurrent use.

• Tablets: 150 mg;
• Oral granules: 25 mg/pkt; 50 mg/pkt; 75 mg/pkt;

• PO (Adults and Children 6 yr): 150 mg every 12 hr with fat-containing food (use tablets); Concurrent use of strong CYP3A inhibitors — 150 mg twice weekly (use tablets); Concurrent use of moderate CYP3A inhibitors — 150 mg once daily (use tablets).
• PO (Children 6 mo–<6 yr and 14 kg): 75 mg every 12 hr with fat-containing food (use oral granules); Concurrent use of strong CYP3A inhibitors — 75 mg twice weekly (use oral granules); Concurrent use of moderate CYP3A inhibitors — 75 mg once daily (use oral granules).
• PO (Children 6 mo–<6 yr and 7–<14 kg): 50 mg every 12 hr with fat-containing food (use oral granules); Concurrent use of strong CYP3A inhibitors — 50 mg twice weekly (use oral granules); Concurrent use of moderate CYP3A inhibitors — 50 mg once daily (use oral granules).
• PO (Children 6 mo–<6 yr and 5–<7 kg): 25 mg every 12 hr with fat-containing food (use oral granules); Concurrent use of strong CYP3A inhibitors — 25 mg twice weekly (use oral granules); Concurrent use of moderate CYP3A inhibitors — 25 mg once daily (use oral granules).
• PO (Children 4 mo–<6 mo and 5 kg): 25 mg every 12 hr with fat-containing food (use oral granules); Concurrent use of strong CYP3A inhibitors — 25 mg twice weekly (use oral granules); Concurrent use of moderate CYP3A inhibitors — 25 mg once daily (use oral granules).

Kalydeco

• Acts as a potentiator of the CFTR protein (a chloride channel on the surface of endothelial cells) facilitating chloride transport by increasing the channel-open probability (gating).

• Improved lung function with increased weight, decreased exacerbations and CF symptoms.

Therapeutic Classification: cystic fibrosis therapy adjuncts

Pharmacologic Classification: transmembrane conductance regulator potentiators

Absorption: Some absorption follows oral administration; absorption in enhanced 4–8 fold by fat-containing foods.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Extensively metabolized by the liver, mostly by the CYP3A isoenzymes; one metabolite (M1) is pharmacologically active; 87.8% eliminated in feces, negligible urinary elimination.

Half-life: 12 hr.

(blood levels)

†Improved lung function and symptoms.

• Instruct patient to take as directed with a fat-containing meal to increase absorption. Fat-containing foods include eggs, butter, peanut better, cheese pizza. If a missed dose is remembered within 6 hr, take missed dose. If more than 6 hr, skip dose and take next dose at regular time; do not double doses.
• Advise patient to avoid eating grapefruit or Seville oranges or drinking grapefruit juice during therapy.
• Advise patient to notify health care professional if symptoms of liver problems (pain or discomfort in right abdominal area, yellowing of skin or whites of eyes, loss of appetite, nausea, vomiting, dark amber-colored urine) occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
• Emphasize the importance of blood tests to monitor liver function.

EYE-va-KAF-tor