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 ?
NASDAQ: VRTX) is initiating a Phase 3 study of VX-659, tezacaftor, and ivacaftor as an investigational triple combination regimen for people with cystic fibrosis who have two copies of the F508del mutation, the company said.
Vertex announced that it is initiating a Phase 3 study of VX-659, tezacaftor and ivacaftor as an investigational triple combination regimen for people with cystic fibrosis, or CF, who have two copies of the F508del mutation, the most common genetic form of the disease.
Orkambi is a combination of two drugs - lumacaftor and ivacaftor - and is the first therapy to treat the cause of the illness and not just the symptoms.
Although the palmar eruptions are self-resolving, one report found that the use of ivacaftor, a pharmacologic potentiator of the CF transmembrane conductance regulator, in CF patients with aquagenic keratoderma resulted in decrease in both sweat chloride content and in palmar wrinkling after immersion in water.
Cystic fibrosis sufferer Chloe Ryan, four, needs the "wonder drug" Kalydeco, also known as Ivacaftor, to improve her quality of life.
116) For example, the cystic fibrosis drug, ivacaftor (Kalydeco[R]), is priced at roughly $300,000 per patient per year.
After months of campaigning by #hawlifyw, set up by Irfon, the Government bowed to pressure in December, confirming Cetuximab and cystic fibrosis drug Ivacaftor are to be made routinely available to patients in Wales.
The first such available medication was ivacaftor in 2012.
Ivacaftor is the first medicine to treat the underlying cause of cystic fibrosis - other treatments only alleviate the symptoms of the condition - and represents a "signifi-cant step" forward in treatment.
Health Minister Mark Drakeford has also approved a recommendation that Ivacaftor, also known as Kalydeco, which is used to treat cystic fibrosis, should be made available to a wider range of people suffering from the condition.
The other major event is the anticipated Food and Drug Administration approval of a fixed-dose combination of ivacaftor and lumacaftor, a combined potentiator and corrector of the CF transmembrane conductance regulator (CFTR).
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.