eliglustat

(redirected from Cerdelga)

eliglustat

(e-lig-lu-stat),

Cerdelga

(trade name)

Classification

Therapeutic: orphan drugs
Pharmacologic: temporary class
Pregnancy Category: C

Indications

Long term treatment of adults with Gaucher disease type 1 who have been tested to be extensive metabolizers (EMs), intermediate metabolizers (IMs) or poor metabolizers (PMs) of the CYP2D6 enzyme system.

Action

Acts as a specific inhibitor of glucosylceramide synthase, thereby reducing the substrate that accumulates in Gaucher disease type 1.

Therapeutic effects

Improvement in symptoms of Gaucher’s disease (anemia, thrombocytopenia, bone disease, splenomegaly, and hepatomegaly).

Pharmacokinetics

Absorption: EMs—5% absorbed following oral administration (due to extensive first-pass metabolism).
Distribution: Distributes mainly into plasma.
Metabolism and Excretion: Extensively metabolized, primarily by the CYP2D6 enzyme system, with some metabolism by CYP3A4; 41.8% excreted in urine and 51.4% in feces mostly as metabolites.
Half-life: EMs—6.5 hr; PMs—8.9 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown1.5–2 hr (EMs), 3 hr (PMs)12–24 hr

Contraindications/Precautions

Contraindicated in: CYP2D6 ultra-rapid metabolizers (may not achieve effective concentrations); Concurrent use of strong or moderate CYP2D6 inhibitors in patients who are CYP2D6 EMs or IMs (risk of adverse cardiac events); Concurrent use of strong CYP3A inhibitors in patients who are CYP2D6 PMs or IMs (risk of adverse cardiac events); History of cardiac disease, Long QT syndrome, or concurrent use of Class IA or Class III anti-arrhythmics; Concurrent ingestion of grapefruit/grapefruit juice; Moderate or severe renal impairment; Hepatic impairment; Lactation: Discontinue eliglustat or discontinue breastfeeding.
Use Cautiously in: CYP2D6 indeterminate metabolizers (dose not known); Obstetric: Use only if potential maternal benefit justifies risk to fetus; Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)
  • headache (most frequent)
  • dizziness

Cardiovascular

  • palpitations

Gastrointestinal

  • diarrhea (most frequent)
  • flatulence (most frequent)
  • nausea (most frequent)
  • oropharyngeal pain (most frequent)
  • upper abdominal pain (most frequent)
  • constipation
  • reflux

Dermatologic

  • rash

Musculoskeletal

  • arthralgia (most frequent)
  • back pain (most frequent)
  • extremity pain (most frequent)

Interactions

General

Drug-Drug interaction

Concurrent use of strong CYP3A inducers including carbamazepine, phenobarbital, phenytoin, and rifampin may ↓ blood levels and effectiveness (concurrent use not recommended).May ↑ blood levels and effects/risk of toxicity with drugs that are P-gp substrates including digoxin (↓ digoxin dose by 30% and monitor digoxin levels), colchicine, dabigatran, and phenytoin (monitor drug levels, consider dose reduction/titration). May ↑ blood levels and effects/risk of toxicity with drugs that are CYP2D6 substrates including metoprolol, tricyclic antidepressants , and phenothiazines (monitor drug levels, consider dose reduction/titration). Concurrent use of Class IA anti-arrhythmics (including procainamide and quinidine ) or Class III anti-arrhythmics (including amiodarone and sotalol ) ↑ risk of potentially serious adverse cardiac events (concurrent use not recommended).St. John's wort ↓ blood levels and may ↓ effectiveness (concurrent use not recommended).Grapefruit/grapefruit juice ↑ risk of potentially serious adverse cardiac events (concurrent ingestion contraindicated).

Interactions

For extensive metabolizers (EMs)

Drug-Drug interaction

Concurrent use of strong or moderate CYP2D6 inhibitors plus strong or moderate CYP3A inhibitors with eliglustat ↑ risk of potentially serious cardiac events (concurrent use contraindicated).Concurrent use of strong inhibitors of CYP2D6 including paroxetine ↑ risk of potentially serious cardiac events (once daily dosing recommended). Concurrent use of moderate inhibitors of CYP2D6 including terbinafine ↑ risk of potentially serious cardiac events (once daily dose recommended). Concurrent use of strong inhibitors of CYP3A including ketoconazole ↑ risk of potentially serious cardiac events (once daily dose recommended). Concurrent use of moderate inhibitors of CYP3A including fluconazole ↑ risk of potentially serious cardiac events (once daily dose recommended).

Interactions

For intermediate metabolizers (IMs)

Drug-Drug interaction

Concurrent use of strong or moderate CYP2D6 inhibitors plus strong or moderate CYP3A inhibitors with eliglustat ↑ risk of potentially serious cardiac events (concurrent use contraindicated).Concurrent use of strong inhibitors of CYP2D6 including paroxetine ↑ risk of potentially serious cardiac events (once daily dose recommended). Concurrent use of moderate inhibitors of CYP2D6 including terbinafine ↑ risk of potentially serious cardiac events (once daily dose recommended). Concurrent use of strong inhibitors of CYP3A including ketoconazole ↑ risk of potentially serious cardiac events (concurrent use contraindicated). Concurrent use of moderate inhibitors of CYP3A including fluconazole ↑ risk of potentially serious cardiac events (concurrent use not recommended).

Interactions

For poor metabolizers (PMs)

Drug-Drug interaction

Concurrent use of strong inhibitors of CYP3A including ketoconazole ↑ risk of potentially serious cardiac events (concurrent use contraindicated). Concurrent use of moderate inhibitors of CYP3A including fluconazole ↑ risk of potentially serious cardiac events (concurrent use not recommended). Concurrent use of weak inhibitors of CYP3A including ranitidine ↑ risk of potentially serious cardiac events (concurrent use not recommended).

Route/Dosage

Oral (Adults) CYP2D6 EMs or IMs—84 mg twice daily; CYP2D6 PMs—84 mg once daily; CYP2D6 EMs or IMs taking strong or moderate CYP2D6 inhibitors or CYP2D6 EMs taking strong or moderate CYP3A inhibitors—84 mg once daily.

Availability

Capsules: 84 mg

Nursing implications

Nursing assessment

  • Monitor for an improvement in symptoms including hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone demineralization, and increased appetite and energy level periodically duting therapy. Assess liver and spleen size every 6 mo to determine effectiveness of therapy.

Potential Nursing Diagnoses

Fatigue (Indications)
Risk for injury (Indications)

Implementation

  • Administer 24 hr after last dose of imiglucerase, taliglucerase, or velaglucerase.
  • Oral: Administer without regard to food, preferably with water. Swallow capsules whole; do not open, crush or chew.

Patient/Family Teaching

  • Instruct patient to take eliglustat as directed. Omit missed doses and take next scheduled dose; do not double doses. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
  • Advise patient to avoid grapefruit and grapefruit juice during therapy.
  • Inform patient of the purpose of this medication and the importance of treatment at least every 4 wk. Eliglustst helps control the symptoms but does not cure Gaucher’s disease. Lifelong therapy may be required.
  • Advise patient to notify health care professional if palpitations, fainting, or dizziness occur.
  • Advise 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 female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
  • Emphasize the importance of follow-up examinations and lab tests.

Evaluation/Desired Outcomes

  • Improvement in symptoms of Gaucher’s disease (anemia, thrombocytopenia, bone disease, splenomegaly, and hepatomegaly).
References in periodicals archive ?
II-62 Johnson & Johnson Acquires Alios BioPharma II-62 PDL Biopharma Acquires Part of Cerdelga Royalties II-62 DPx Holdings B.
Food and Drug Administration today approved Cerdelga (eliglustat) for the long-term treatment of adult patients with the Type 1 form of Gaucher disease, a rare genetic disorder.
Cerdelga is a hard gelatin capsule containing eliglustat that is taken orally.
In addition, Cerdelga received orphan drug designation from the FDA, reflecting the agency s focus and commitment to the development of treatments for rare diseases.
The safety and effectiveness of Cerdelga were evaluated in two clinical trials with 199 participants with Type 1 Gaucher disease.
In addition to the recent FDA approval, marketing applications for Cerdelga are under review by the European Medicines Agency and other regulatory authorities.
Genzyme's clinical development program for Cerdelga represented the largest clinical program ever conducted in Gaucher disease, with approximately 400 patients treated in 29 countries.
Our acquisition of the Cerdelga royalties significantly adds to our already diversified portfolio of biopharmaceutical royalties," stated John McLaughlin, president and chief executive officer of PDL BioPharma.
Further, the Cerdelga clinical development program is the largest ever conducted in Gaucher disease, with approximately 400 patients treated in 29 countries.
During the next three quarters of 2014, we expect important development milestones for multiple high potential pipeline projects including Toujeo(TM) (U300), the Dengue vaccine, alirocumab, Cerdelga and dupilumab.
On December 11, 2013, Sanofi SA (Sanofi), along with its subsidiary Genzyme, announced that the FDA has granted a six-month Priority Review designation to Genzyme's NDA for Cerdelga (eliglustat), an investigational oral therapy for adult patients with Gaucher disease type 1.