Cerdelga (eliglustat)

Cerdelga is a capsule taken by mouth for the long-term treatment of adults with Gaucher disease type 1.

The disease: Gaucher disease type 1 is an inherited condition in which a fatty substance builds up in the spleen, liver, and bone marrow because the enzyme that breaks it down is missing or weak.

Who can take it: It is approved only for people whose CYP2D6 gene test, done with an FDA-cleared test, shows they are extensive, intermediate, or poor metabolizers.

Who cannot: People who are ultra-rapid metabolizers may not reach a high enough drug level for it to work, and no dose can be recommended when the test result is indeterminate.

Children: It has not been studied in children.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

Eliglustat tartrate is the salt form of eliglustat used in Cerdelga capsules, and Cerdelga is made by Genzyme Corporation, the rare disease arm of Sanofi, often written as Sanofi Genzyme.

Capsule strength: Each capsule holds 100 mg of eliglustat tartrate, which equals 84 mg of active eliglustat, so the dose is written as 84 mg.

What it is: The drug is a small molecule built to resemble ceramide, the natural building block that the target enzyme normally uses.

Drug class and approval: It belongs to a class called substrate reduction therapy and was approved by the FDA in August 2014 as the first oral first-line treatment for Gaucher disease type 1.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

Eliglustat blocks the enzyme that makes the fat that builds up in Gaucher disease, so less of it is produced.

The disease: Gaucher disease is caused by a shortage of an enzyme called acid beta-glucosidase, which normally breaks down a fat called glucosylceramide (also called glucocerebroside or GL-1).

What goes wrong: Without enough enzyme, GL-1 piles up inside immune cells called macrophages, turning them into swollen Gaucher cells that crowd the spleen, liver, and bone marrow and cause enlarged organs, anemia, low platelets, and bone problems.

How eliglustat helps: Eliglustat works upstream: it blocks glucosylceramide synthase, the enzyme that makes GL-1 in the first place, so less of it is produced and the body's remaining enzyme activity can keep up.

Drug class: This approach is called substrate reduction therapy, in contrast to enzyme replacement therapy, which supplies the missing enzyme by IV infusion.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

Across the 2 main trials, the side effects reported by at least 10% of the 126 patients on Cerdelga were fatigue, headache, nausea, diarrhea, back pain, pain in the arms or legs, and upper belly pain.

Switch trial: In the trial of patients switching from enzyme replacement, the rates on Cerdelga versus imiglucerase were fatigue 14% vs 2%, headache 13% vs 2%, nausea 12% vs 0%, diarrhea 12% vs 4%, back pain 12% vs 6%, limb pain 11% vs 2%, and upper belly pain 10% vs 0%, with dizziness, weakness, cough, indigestion, acid reflux, constipation, palpitations, and rash each at 5% to 8%.

Placebo trial: In the small placebo-controlled trial of 40 untreated patients, joint pain was the standout at 45% vs 10% on placebo, with headache at 40% vs 30%.

Serious concern: The main serious concern is a possible effect on heart rhythm at high blood levels, covered below.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

At very high blood levels, eliglustat is predicted to lengthen the PR, QRS, and QT intervals on an ECG, which could raise the risk of an abnormal heart rhythm.

What studies showed: At 8 times the recommended dose it did not prolong the QT interval to a clinically important degree, but modeling predicts increases of about 22, 7, and 13 milliseconds in those intervals when the blood level reaches 500 ng/mL, far above normal dosing.

Who should avoid it: Because of this, the label says to avoid Cerdelga in people with existing heart disease such as heart failure, a recent heart attack, slow heart rate, heart block, or ventricular arrhythmia, in people with long QT syndrome, and in people taking Class IA or Class III antiarrhythmic drugs such as quinidine, amiodarone, or sotalol.

Biggest risk: The biggest real-world risk is other drugs that push eliglustat levels up, which is why the interaction rules are strict.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

Oral bioavailability, the fraction of a swallowed dose that reaches the bloodstream, is less than 5% for eliglustat in CYP2D6 extensive metabolizers after a single 84 mg dose, because the liver clears most of it on the first pass.

Why CYP2D6 matters: That first-pass effect is why drug levels depend so heavily on CYP2D6 status: poor metabolizers have 7 to 9 times the exposure of extensive metabolizers at the same twice-daily dose.

Peak and half-life: Eliglustat peaks in the blood about 1.5 to 3 hours after a dose and has a half-life of about 6.5 hours in extensive metabolizers and 8.9 hours in poor metabolizers.

Food: A high-fat meal lowers the peak by about 15% without changing total exposure, so you can take it with or without food.

Elimination: It leaves the body mostly as metabolites, 42% in urine and 51% in stool.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

The dose depends on your CYP2D6 gene test: extensive and intermediate metabolizers take 84 mg twice a day, and poor metabolizers take 84 mg once a day.

How to take: Swallow the capsules whole with water, do not crush, open, or dissolve them, and avoid grapefruit and grapefruit juice because they block the CYP3A enzyme and raise drug levels.

Missed dose: If you miss a dose, take the next one at its usual time rather than doubling up.

Dose changes: Extensive and intermediate metabolizers may be moved down to once daily if they have mild liver impairment or take certain CYP2D6 or CYP3A inhibitors.

Switching: Anyone switching from enzyme replacement can start Cerdelga 24 hours after their last infusion.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

The label requires an FDA-cleared CYP2D6 genotype test before prescribing because the right dose and the interaction rules are different for each metabolizer group.

What CYP2D6 is: CYP2D6 is the liver enzyme that does most of the work clearing eliglustat, and people inherit versions of the gene that make it fast, normal, slow, or barely active.

Why it matters: Poor metabolizers reach 7 to 9 times the drug level of extensive metabolizers on the same dose.

Excluded groups: Ultra-rapid metabolizers clear the drug so fast they may never reach a working level, and people whose result is indeterminate cannot be given a reliable dose, so neither group should take Cerdelga.

One-time test: Your result does not change over time, so the test only needs to be done once.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

Any medicine that blocks CYP2D6 or CYP3A can push eliglustat levels up.

Measured increases: The strong CYP2D6 blocker paroxetine raised exposure 8.4-fold in extensive metabolizers, the strong CYP3A blocker ketoconazole raised it 4.4-fold, and taking both together raised it 24.2-fold, which is why that combination is contraindicated.

Rules by metabolizer type: Depending on your metabolizer type, strong or moderate blockers either require a drop to once-daily dosing, must be avoided, or are contraindicated outright; strong CYP3A inhibitors are contraindicated for intermediate and poor metabolizers.

Inducers: Strong CYP3A inducers such as rifampin cut eliglustat levels by 90% to 95% and should be avoided.

Drugs eliglustat raises: Eliglustat also raises levels of digoxin (reduce the digoxin dose by 30% and monitor) and of CYP2D6-dependent drugs like metoprolol, which rose 2.3-fold, so always give your doctor and pharmacist a full medication list.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

No generic eliglustat is listed in our records, and the current FDA label describes only brand-name Cerdelga from Genzyme.

What an ANDA is: An ANDA is an abbreviated new drug application, the paperwork a company files to get a generic approved, and the label does not tell us whether any company has filed one.

What to do: If a generic is ever approved it would appear in the FDA's list of approved drug products, so ask your pharmacist to check rather than assuming.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

The FDA label does not list a price, and we do not publish one because the amount you pay depends on your insurance, deductible, and pharmacy.

What to expect: Cerdelga is a specialty medicine for a rare disease, so expect prior authorization and a specialty pharmacy.

Assistance: Our entry for eliglustat does not list a named manufacturer support program, so ask Sanofi Genzyme directly or have your treating specialist's office check what copay or free-drug help is available for your coverage.

Cerdelga shrank the spleen and improved blood counts versus placebo in untreated patients, and kept most patients stable after a switch from enzyme replacement.

ENGAGE design: The ENGAGE trial (Trial 1 on the label) compared Cerdelga with placebo in 40 adults who had not been treated before, over 9 months.

ENGAGE results: Spleen volume shrank by 27.8% on Cerdelga while it grew 2.3% on placebo, a 30% difference; hemoglobin rose 1.2 g/dL more, liver volume was 6.6% smaller, and platelet counts were 41.1% higher relative to placebo. Patients who stayed on the drug for 2 years saw spleen volume fall 51.1% and platelets rise 65.3% from where they started.

ENCORE results: The ENCORE trial (Trial 2) tested whether people could switch from enzyme replacement without losing ground, and it met its goal: after 12 months, 84.8% of Cerdelga patients stayed stable on all 4 measures (hemoglobin, platelets, liver size, spleen size) versus 93.6% on imiglucerase, within the margin set in advance.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

Yes, if your CYP2D6 test allows it.

ENCORE trial: In the ENCORE trial, 159 adults who had been on enzyme replacement for at least 3 years and had reached treatment goals were switched to Cerdelga or kept on imiglucerase, and the Cerdelga group held steady on blood counts and organ size over 12 months, meeting the trial's non-inferiority goal.

Longer follow-up: In the longer extension, 85% of patients remained stable after 1 year and 86% after 2 years on Cerdelga.

Timing: You can take your first Cerdelga dose 24 hours after your last imiglucerase, velaglucerase alfa, or taliglucerase alfa infusion.

Backup option: Enzyme replacement remains an option if Cerdelga is not right for you.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

Beyond the CYP2D6 groups it is not approved for, Cerdelga is contraindicated in several situations because of the heart rhythm risk.

Extensive metabolizers: Extensive metabolizers must not take it with moderate or severe liver impairment, or with mild liver impairment plus a strong or moderate CYP2D6 inhibitor.

Intermediate and poor metabolizers: They must not take it with any degree of liver impairment or with a strong CYP3A inhibitor.

All metabolizer types: Any metabolizer type must avoid combining a strong or moderate CYP2D6 inhibitor with a strong or moderate CYP3A inhibitor, and the label advises against use in people with existing heart disease or long QT syndrome.

Children: Its effects in people under 18 have not been established.

Source: FDA label for Cerdelga, DailyMed, effective 2024-03-03

Both are oral substrate reduction therapies for Gaucher disease, but they have different roles.

Role: Eliglustat is approved as a first-line treatment, while miglustat is generally used second-line for people who cannot receive enzyme replacement.

Side effects: Eliglustat also has a different side effect pattern, with fewer gastrointestinal problems than miglustat.

Testing: Eliglustat requires a CYP2D6 gene test before starting and has strict drug interaction rules tied to that result.

Eliglustat was the first oral treatment approved as a first-line option for Gaucher disease type 1 when the FDA cleared it in August 2014.

Miglustat: Miglustat (Zavesca) was approved earlier, in 2003, but only for people who could not receive enzyme replacement therapy.

What it changed: Cerdelga gave eligible adults an alternative to IV enzyme infusions every 2 weeks, with the trade-off of a required gene test and careful attention to drug interactions.