ivacaftor

ivacaftor

(eye-va-kaf-tor) ,

Kalydeco

(trade name)

Classification

Therapeutic: cystic fibrosis therapy adjuncts
Pharmacologic: temporary class
Pregnancy Category: B

Indications

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.

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.

Pharmacokinetics

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

ROUTEONSETPEAKDURATION
POwithin 1 wk†4 hr12 hr
†Improved lung function and symptoms.

Contraindications/Precautions

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)
  • dizziness

Ear, Eye, Nose, Throat

  • nasal congestion (most frequent)
  • oropharyngeal pain

Gastrointestinal

  • nausea (most frequent)
  • abdominal pain
  • diarrhea
  • ↑ liver enzymes

Dermatologic

  • rash (most frequent)

Musculoskeletal

  • arthralgia
  • musculoskeletal chest pain
  • mylagia

Endocrinologic

  • hyperglycemia
  • hypoglycemia

Interactions

Drug-Drug interaction

Strong 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.

Route/Dosage

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 Impairment

Oral (Adults and Children ≥6 yr) Moderate hepatic impairment—150 mg once daily; Severe hepatic impairment—150 mg once daily or less.

Availability

Tablets: 150 mg

Nursing implications

Nursing assessment

  • 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 Diagnoses

Deficient knowledge, related to disease process and medication regimen (Patient/Family Teaching)

Implementation

  • Oral: Administer with fat-containing food.

Patient/Family Teaching

  • 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.

Evaluation/Desired Outcomes

  • Improved lung function with increased weight, decreased exacerbations and symptoms in patients with cystic fibrosis.
References in periodicals archive ?
Clinical Pharmacology Profile of Ivacaftor, a CFTR Potentiator.
Overall, the incidence and clinical features of transaminase elevations in clinical trials was similar between subjects in the ivacaftor and placebo treatment groups.
Vertex Pharmaceuticals Incorporated (NASDAQ: VRTX) announced results from two Phase 3 studies of lumacaftor in combination with ivacaftor that showed statistically significant improvements in lung function (percent predicted forced expiratory volume in one second, or ppFEV[sub.
Lumacaftor was designed to move the F508del protein to the cell surface where its activity can be increased by a potentiator drug such as ivacaftor.
1: Cystic Fibrosis: ivacaftor (Kalydeco) 319 Appendix 2.
On December 19, 2013, Vertex Pharmaceuticals Incorporated (Vertex) announced data from a Phase 3 study of ivacaftor in 69 people 6 years of age and older with cystic fibrosis (CF) who have the R117H mutation.
The submission was based on preclinical and clinical data showing the effect of ivacaftor on CFTR function in certain residual function mutations.
The combination of drugs lumacaftor and ivacaftor are designed to repair abnormal genes.
8 billion, the breast cancer drug Ibrance (palbociclib) is the second oncologic drug making the blockbuster list, with the first noncancer or non-CV drug--lumacaftor plus ivacaftor for cystic fibrosis rounding out the Top 5 with projected sales of $2.
Medics say ivacaftor, known as Kalydeco, can radically transform the health of users and is predicted to increase life expectancy.