CERDELGA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CERDELGA (CERDELGA).
Cerdelga (eliglustat) is a glucosylceramide synthase inhibitor that reduces the synthesis of glucosylceramide, the substrate that accumulates in Gaucher disease type 1.
| Metabolism | Primarily metabolized by CYP2D6, with minor contribution from CYP3A4. |
| Excretion | Primarily hepatic metabolism (UGT2B7, UGT1A4, P450) and biliary excretion; unchanged drug is the primary entity in plasma. Fecal elimination accounts for approximately 92% of the administered dose (largely as unchanged drug), with renal excretion of unchanged drug representing <2% of the dose. |
| Half-life | 12–20 hours (median ~14 hours). Steady-state is reached within 7–10 days. The half-life supports twice-daily dosing. |
| Protein binding | Approximately 99.5% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 60–120 L (≈1.0 L/kg based on typical adult weight). High Vd indicates extensive tissue distribution, particularly to liver and spleen (target organs for Gaucher disease). |
| Bioavailability | Oral bioavailability is not directly determined; absolute bioavailability is estimated to be >70% based on area under the curve (AUC) comparisons with intravenous data (if available). Administration with food increases exposure by ~50% (high-fat meal increases AUC by ~60%). |
| Onset of Action | Clinical improvement in glucosylceramide accumulation is expected within 2–4 weeks of continuous oral administration, based on biomarker reductions (glucosylceramide and glucosylsphingosine levels). Full therapeutic response may require 6–12 months for bone pain and organomegaly. |
| Duration of Action | Duration of effect is approximately 12 hours, consistent with dosing interval of 84 mg twice daily for sustained substrate reduction. Clinical effects persist with continuous therapy; effects wane if doses are missed. |
84 mg orally twice daily.
| Dosage form | CAPSULE |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73m²). Not studied in severe renal impairment (eGFR <30 mL/min/1.73m²) or end-stage renal disease. |
| Liver impairment | Contraindicated in patients with severe hepatic impairment (Child-Pugh class C). For moderate impairment (Child-Pugh class B), reduce dose to 84 mg orally once daily. For mild impairment (Child-Pugh class A), no dose adjustment. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended. Consider age-related decline in renal function; monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CERDELGA (CERDELGA).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Caution advised; consider developmental benefits of breastfeeding versus mother's need for therapy. |
| Teratogenic Risk | No well-controlled studies in pregnant women. Animal studies have shown no evidence of teratogenicity at clinically relevant doses. Risk of fetal harm cannot be ruled out; use only if benefit justifies potential risk. First trimester: theoretical risk based on mechanism (glucosylceramide synthase inhibition), but no human data. Second and third trimesters: limited data; no specific fetal adverse effects reported. |
■ FDA Black Box Warning
None
| Serious Effects |
["CYP2D6 ultra-rapid metabolizers (not expected to achieve therapeutic concentrations).","Concomitant use with strong or moderate CYP2D6 inhibitors and strong CYP3A4 inhibitors in CYP2D6 poor metabolizers.","Pre-existing cardiac conduction abnormalities (e.g., second- or third-degree AV block, sick sinus syndrome) without a pacemaker.","Hypersensitivity to eliglustat or any of its excipients."]
| Precautions | ["CYP2D6 poor metabolizers have significantly higher drug exposure and require lower dosing; testing for CYP2D6 status is required before initiating therapy.","Avoid use in CYP2D6 ultra-rapid metabolizers due to lack of efficacy.","Concomitant use with strong or moderate CYP2D6 inhibitors and strong CYP3A4 inhibitors is contraindicated in poor metabolizers; in extensive and intermediate metabolizers, dose adjustment may be needed.","Potential for QTc prolongation at supratherapeutic doses; monitor ECG if co-administered with drugs that prolong QTc or in patients with cardiac disease.","Not recommended in patients with pre-existing cardiac disease (e.g., heart failure, recent myocardial infarction, bradycardia) unless benefits outweigh risks.","Monitor for development of new or worsening cardiac arrhythmias."] |
Loading safety data…
| Fetal Monitoring | No specific fetal monitoring required. Monitor maternal liver function tests (LFTs) and complete blood count (CBC) as per standard product prescribing. For pregnant women, consider periodic LFTs, CBC, and assessment for adverse effects. |
| Fertility Effects | No data on impairment of fertility in humans. Animal studies have shown no adverse effects on fertility at clinically relevant doses. Theoretical potential for hormonal disruption due to glucosylceramide synthase inhibition, but significance unknown. |
| Food/Dietary |
| Avoid grapefruit and grapefruit juice, star fruit (carambola), and blood oranges due to potential CYP3A4 inhibition and increased drug exposure. |
| Clinical Pearls | Cerdelga (eliglustat) is a glucosylceramide synthase inhibitor used for Gaucher disease type 1 (GD1). Assess CYP2D6 metabolizer status before initiating; poor metabolizers (PMs) require lower dose (84 mg once daily) while extensive (EMs), intermediate (IMs), and ultrarapid metabolizers (UMs) receive 84 mg twice daily. Avoid use in PMs with moderate or severe hepatic impairment. Monitor for cardiac effects (QT prolongation) and drug interactions via CYP2D6 and CYP3A4. Baseline ECG recommended. Not recommended in patients with pre-existing cardiac disease (e.g., long QT syndrome). Cerdelga is not interchangeable with imiglucerase or velaglucerase alfa. |
| Patient Advice | Take Cerdelga capsules whole with or without food at the same times each day. · If you miss a dose, skip it and take the next dose at the regular time; do not double the dose. · Avoid grapefruit and grapefruit juice, as well as star fruit and blood oranges, while taking this medication. · Inform your healthcare provider of all medications you take, including over-the-counter drugs and supplements, due to potential interactions. · Cardiac monitoring (ECG) may be needed; report any palpitations, fainting, or dizziness. · Genetic testing for CYP2D6 metabolizer status is required before starting treatment to determine the correct dose. · Do not switch between Cerdelga and other Gaucher disease therapies without medical advice. |