Eliglustat

What is Eliglustat?

• Eliglustat (CERDELGA) is a glucosylceramide synthase inhibitor used for the treatment of Gaucher's disease.

What are the uses of this medicine?

• This medicine used for the long-term treatment of Gaucher disease type 1 (GD1) in adults.

Limitations of Use:

• Patients who are CYP2D6 ultra-rapid metabolizers (URMs) may not achieve adequate concentrations of CERDELGA to achieve a therapeutic effect.
• A specific dosage cannot be recommended for those patients whose CYP2D6 genotype cannot be determined (indeterminate metabolizers).

How does this medicine work?

• Eliglustat (el" i gloo' stat) is a small molecule inhibitor of glucosylceramide synthase, the first and rate controlling step in the pathway of glycolipid synthesis.
• By inhibiting the pathway, lower levels of gylcolipid substrates are available, so that less of the substrate is available for lysosomal degradation and less glycosylceramide accumulates.
• Eliglustat was shown to decrease the intracellular accumulation of glycosylceramide in animal models of Gaucher disease.
• In several randomized controlled trials, eliglustat was shown to decrease spleen and liver volume and increase hemoglobin and platelet counts in patients with type 1 Gaucher disease.
• Eliglustat was also able to maintain clinical benefit in patients who had been maintained on long term enzyme replacement therapy with glucocerebrosidase infusions (the lysosomal enzyme that is deficient in type 1 Gaucher disease).

Who Should Not Use this medicine ?

CERDELGA is contraindicated in the following patients based on CYP2D6 metabolizer status.

EMs

• Taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor.
• Moderate or severe hepatic impairment.
• Mild hepatic impairment and taking a strong or moderate CYP2D6 inhibitor.

IMs

• Taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor.
• Taking a strong CYP3A inhibitor.
• Any degree of hepatic impairment.

PMs

• Taking a strong CYP3A inhibitor.
• Any degree of hepatic impairment.

What drug interactions can this medicine cause?

• CYP2D6 or CYP3A inhibitors may increase eliglustat concentrations which may increase the risk of cardiac arrhythmias from prolongation of the PR, QTc, and/or QRS cardiac interval.
• strong CYP3A inducers decrease eliglustat concentrations which may reduce CERDELGA efficacy.
• Coadministration of CERDELGA may increase concentrations of drugs that are substrates for P-gp or CYP2D6 and may increase the risk of toxicity of these drugs.
• Monitor serum digoxin concentrations before initiating CERDELGA. Reduce digoxin dose by 30% and continue monitoring.

Is this medicine FDA approved?

• This medicine is approved in the year 2014.

How should this medicine be used?

• Select patients with Gaucher disease type 1 based on their CYP2D6 metabolizer status.

Recommended Dosage:

Recommended Dosage Based on CYP2D6 Metabolizer Status:

• EMs and IMs: 84 mg orally twice daily.
• PMs: 84 mg orally once daily.

Administration

• Take CERDELGA exactly as your doctor tells you to take it.
• Your doctor may change your dose if needed.
• Take CERDELGA capsules whole, preferably with water. Do not open, crush, or dissolve capsules before swallowing.
• CERDELGA can be taken with or without food.
• If you miss a dose of CERDELGA, take the next dose at the usual time. Do not take two doses of CERDELGA at the same time.
• If you take too much CERDELGA, call your doctor or go to the nearest hospital emergency room right away.'

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: 84 mg eliglustat

This medicine is available in fallowing brand namesː

• CERDELGA

What side effects can this medication cause?

The most common side effects of this medicine include:

• tiredness
• headache
• nausea
• diarrhea
• pain in the arms, legs, back, or stomach (abdomen)

What special precautions should I follow?

• CERDELGA is predicted to cause increases in ECG intervals (PR, QTc, and QRS) at substantially elevated eliglustat plasma concentrations and may increase the risk of cardiac arrhythmias.
• Use of CERDELGA is contraindicated, to be avoided, or requires dosage adjustment in patients taking CYP2D6 or CYP3A inhibitors, depending on CYP2D6 metabolizer status, type of inhibitor, or degree of hepatic impairment.

Avoid use of CERDELGA in patients with:

• pre-existing cardiac disease (congestive heart failure, recent acute myocardial infarction, bradycardia, heart block, ventricular arrhythmia)
• long QT syndrome
• in combination with Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications

Avoid eating or drinking grapefruit products while taking CERDELGA. Grapefruit products can increase the amount of CERDELGA in your body.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• dizziness marked by disequilibrium
• hypotension
• bradycardia
• nausea
• vomiting

Management of overdosage:

• In the event of acute overdose, the patient should be carefully observed and given symptomatic and supportive treatment.
• Hemodialysis is unlikely to be beneficial given that eliglustat has a large volume of distribution.

Can this medicine be used in pregnancy?

• These data are not sufficient to assess drug-associated risks major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Can this medicine be used in children?

• Safety and effectiveness in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: eliglustat
• Inactive ingredients: microcrystalline cellulose, lactose monohydrate, hypromellose, glyceryl behenate, gelatin, candurin silver fine, yellow iron oxide, and FD&C blue 2

Who manufactures and distributes this medicine?

• Manufactured by: Genzyme Ireland, Ltd., IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland

CERDELGA is a trademark of Genzyme Corporation

What should I know about storage and disposal of this medication?

• Store CERDELGA at room temperature between 68°F to 77 °F (20°C to 25 °C).
• Keep CERDELGA and all medicines out of reach of children.

• Dailymed label info on Eliglustat
• FDA Eliglustat

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