Pregnancy Category: B
Pharmacologic: temporary class
ClassificationTherapeutic: cystic fibrosis therapy adjuncts
Pharmacologic: temporary class
genetic implication Treatment of cystic fibrosis in patients ≥6 yr with a G551D mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Not effective in patients who are homozygous for the F508del mutation of the CFTR gene.
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.
Absorption: Some absorption follows oral administration; absorption in enhanced 4–8 fold by fat-containing foods.
Protein Binding: >99%.
Metabolism and Excretion: Extensively metabolized, mostly by the CYP3A enzyme system; one metabolite (M1) is pharmacologically active; 87.8% eliminated in feces, negligible urinary elimination.
Half-life: 12 hr.
Time/action profile (blood levels)
|PO||within 1 wk†||4 hr||12 hr|
Contraindicated in: Concurrent use of strong CYP3A inducers.
Use Cautiously in: Moderate to severe hepatic impairment (dose ↓ recommended); Concurrent use of CYP3A inhibitors (dose ↓ recommended); Concurrent use of CYP3A and/or P-gp substrates; Severe renal impairment (CCr <30 mL/min) or end stage renal disease; Obstetric: Use in pregnancy only if clearly needed; Lactation: Use cautiously during breast feeding; Pediatric: Children <6 yr (safety not established).
Adverse Reactions/Side Effects
Central nervous system
- headache (most frequent)
Ear, Eye, Nose, Throat
- nasal congestion (most frequent)
- oropharyngeal pain
- nausea (most frequent)
- abdominal pain
- ↑ liver enzymes
- rash (most frequent)
- musculoskeletal chest pain
Drug-Drug interactionStrong CYP3A inducers including rifampin, rifabutin, phenobarbital, carbamazepine and phenytoin ↓ levels and effectiveness; avoid concurrent useStrong CYP3A inhibitors including ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin may ↑ levels and risk of adverse reactions (dosage ↓ recommended). Moderate CYP3A inhibitors including fluconazole or erythromycin may ↑ levels and risk of adverse reactions (dosage ↓ recommended).May ↑ levels and effects of CYP3A substrates including alprazolam, diazepam, midazolam and triazolam.May ↑ levels and effects of P-gp substrates including digoxin, cyclosporine and tacrolimus.May alter the effects of warfarin.St. John's wort may ↓ levels and effectiveness; avoid concurrent use.Grapefruit or Seville oranges may ↑ levels and ↑ risk of toxicity; avoid concurrent use.
Oral (Adults and Children ≥6 yr) 150 mg q 12 hr with fat-containing food; Concurrent strong CYP3A inhibitors—150 mg twice weekly; cConcurrent moderate CYP3A inhibitors—150 mg once daily.
Hepatic ImpairmentOral (Adults and Children ≥6 yr) Moderate hepatic impairment—150 mg once daily; Severe hepatic impairment—150 mg once daily or less.
Tablets: 150 mg
- Monitor lung function (FEV, lung sounds) before and periodically during therapy.
- Lab Test Considerations: May cause ↑ serum transaminases. Monitor AST and ALT before, every 3 months for the first year, and annually thereafter. If AST or ALT >5 times the upper limit of normal, interrupt therapy. Once AST or ALT have returned to normal, consider the benefits and risks before resuming therapy.
Potential Nursing DiagnosesDeficient knowledge, related to disease process and medication regimen (Patient/Family Teaching)
- Oral: Administer with fat-containing food.
- Instruct patient to take as directed with a fat-containing meal to increase absorption. Fat-containing foods include eggs, butter, peanut better, cheese pizza.
- 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.
- Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
- Emphasize the importance of blood tests to monitor liver function.
- Improved lung function with increased weight, decreased exacerbations and symptoms in patients with cystic fibrosis.