ivacaftor

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

Neuro: headache, dizziness

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A inducers, including rifampin, rifabutin, phenobarbital, carbamazepineand phenytoin↓ levels and effectiveness; avoid concurrent use
Strong CYP3A inhibitors, including ketoconazole, itraconazole, posaconazole, voriconazole, and clarithromycin may ↑ levels and risk of toxicity (↓ dose).
Moderate CYP3A inhibitors, including fluconazoleor erythromycinmay ↑ levels and risk of toxicity (↓ dose).
May ↑ levels and effects of CYP3A substrates, including alprazolam, diazepam, midazolamand triazolam.
May ↑ levels and effects of P-glycoprotein substrates, including digoxin, cyclosporineand 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.

Availability ⬆ ⬇

Tablets: 150 mg
Oral granules: 5.8 mg/pkt; 13.4 mg/pkt; 25 mg/pkt; 50 mg/pkt; 75 mg/pkt
In combination with: elexacaftor and tezacaftor (Trikafta); lumacaftor (Orkambi); and tezacaftor (Symdeko). See Appendix [not included in this PDA edition].

Route/Dosage ⬆ ⬇

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 moderate or strong CYP3A inhibitors: Not recommended.
PO (Children 2 mo–<4 mo and ≥3 kg): 13.4 mg every 12 hr with fat-containing food (use oral granules). Concurrent use of moderate or strong CYP3A inhibitors: Not recommended.
PO (Children 1 mo–<2 mo and ≥3 kg): 5.8 mg every 12 hr with fat-containing food (use oral granules). Concurrent use of moderate or strong CYP3A inhibitors: Not recommended.

Hepatic Impairment

PO (Adults and Children ≥6 yr): Moderate hepatic impairment: 150 mg once daily (use tablets); Severe hepatic impairment: 150 mg once daily or less (use tablets).

Hepatic Impairment

PO (Children 6 mo–<6 yr and ≥14 kg): Moderate hepatic impairment: 75 mg once daily (use oral granules); Severe hepatic impairment: 75 mg once daily or less (use oral granules).

Hepatic Impairment

PO (Children 6 mo–<6 yr and 7–<14 kg): Moderate hepatic impairment: 50 mg once daily (use oral granules); Severe hepatic impairment: 50 mg once daily or less (use oral granules).

Hepatic Impairment

PO (Children 6 mo–<6 yr and 5–<7 kg): Moderate hepatic impairment: 25 mg once daily (use oral granules); Severe hepatic impairment: 25 mg once daily or less (use oral granules).
PO (Children <6 mo and ≥5 kg): Moderate or severe hepatic impairment: Not recommended.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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).

Therapeutic effects:

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

Classifications ⬆ ⬇

Therapeutic Classification: cystic fibrosis therapy adjuncts

Pharmacologic Classification: transmembrane conductance regulator potentiators

Pharmacokinetics ⬆ ⬇

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.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	within 1 wk‡	4 hr	12 hr

‡Improved lung function and symptoms.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take as directed with a fat-containing meal to increase absorption. Fat-containing foods include eggs, butter, peanut butter, and 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.
Rep: 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.

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Indications ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Classifications ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Pronunciation ⬆