Cerdelga: A First Line Oral Therapy for Gaucher Disease Type 1

Cerdelga, a glucosylceramide synthase inhibitor, is a groundbreaking long-term treatment designed for adults with Gaucher disease type 1 identified through an FDA-cleared test as CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs). This concise introduction outlines Cerdelga’s significance in addressing Gaucher disease complexities.

What is Cerdelga? 

Cerdelga (eliglustat) is a first-line oral therapy for the long-term treatment of type 1 Gaucher disease in adults who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test. It is the only first-line oral therapy indicated for most adults with Gaucher disease type 1. 

What Is Type 1 Gaucher disease? 

Type 1 Gaucher disease is a rare genetic disorder caused by the deficiency of the enzyme glucocerebrosidase. This leads to the accumulation of glucocerebroside in cells, particularly macrophages, forming Gaucher cells. Common symptoms include:

• Enlarged spleen and liver
• Bone abnormalities
• Fatigue
• Anemia
• Easy bruising
• Bone fractures

While type 1 Gaucher disease can affect various organs and tissues, it typically does not involve significant neurological symptoms. The age of onset and symptom severity vary among individuals. Inheritance follows an autosomal recessive pattern, requiring the inheritance of mutated genes from both parents for the condition to develop. Treatment options include enzyme replacement therapy or substrate reduction therapy, tailored to individual needs

Mechanism of Action

Cerdelga is a substrate reduction therapy that works by reducing the production of glucocerebroside by partially blocking the enzyme glucosylceramide synthase. This helps to lower the amount of glucocerebroside in the body, which is a fatty substance that accumulates in people with Gaucher disease.

Dosage And Administration

Patient selection involves the use of an FDA-cleared test to determine the CYP2D6 genotype. For CYP2D6 extensive metabolizers (EMs) or intermediate metabolizers (IMs), the recommended dose is 84 mg orally twice daily, while for poor metabolizers (PMs), the suggested dose is Cerdelga 84 mg orally once daily. It is crucial to swallow the capsules whole, without crushing, dissolving, or opening them. Additionally, it is advised to refrain from consuming grapefruit or grapefruit juice.

Side Effects

If you experience signs of an allergic reaction to Cerdelga, such as hives, difficulty breathing, or swelling of the face, lips, tongue, or throat, seek immediate medical attention. Contact your doctor promptly if you encounter sudden dizziness or fast, pounding heartbeats with chest fluttering.

Common side effects of Cerdelga may encompass diarrhea, nausea, stomach pain, headache, fatigue, and back pain. You may also notice pain in your arms or legs. Keep in mind that this is not an exhaustive list of side effects, and there may be others. If you observe any unexpected symptoms, consult your healthcare provider.

Warning and Precaution

• Cerdelga is contraindicated for individuals with severe liver or kidney disease. Additionally, the medication can pose a risk of serious heart problems, particularly when used concurrently with certain other medicines. 
• It is crucial to inform your doctor about all medications you are using, as some drugs may impact the blood levels of eliglustat, potentially causing side effects or reducing its efficacy. 
• Cerdelga may also influence the blood levels of certain medications, either diminishing their effectiveness or increasing side effects. 
• Specifically, caution is advised in patients with pre-existing cardiac disease, long QT syndrome, and those using Class IA and Class III antiarrhythmic drugs. 
• CYP2D6 ultra-rapid metabolizers may not achieve sufficient concentrations of Cerdelga for a therapeutic effect. 
• However, a specific dosage cannot be recommended for CYP2D6 indeterminate metabolizers.

Contraindication

Cerdelga is contraindicated in patients with known hypersensitivity to Eliglustat or any of its components.

Usage in Specific Populations

• In pregnancy, Cerdelga should only be administered if the potential benefit justifies the potential risk, considering that animal data suggest it may cause fetal harm. 
• For nursing mothers, the decision to continue or discontinue the drug should be based on the importance of the drug to the mother. 
• In cases of renal impairment, its use is not recommended in moderate to severe impairment. 
• Similarly, for individuals with hepatic impairment, Cerdelga is not recommended.

Drug Interactions

Eliglustat functions as a substrate for both CYP2D6 and CYP3A. When administered alongside drugs inhibiting these enzymes, there is a potential for increased exposure to eliglustat, leading to the extension of cardiac intervals (PR, QTc, and/or QRS) and the risk of cardiac arrhythmias. 

It is crucial to carefully assess potential drug interactions before and during eliglustat therapy. Specific precautions include avoiding moderate CYP3A inhibitors in CYP2D6 intermediate metabolizers (IMs) and poor metabolizers (PMs). 

Furthermore, since eliglustat acts as an inhibitor of P-glycoprotein (P-gp) and CYP2D6, concurrent use with drugs that are substrates for these enzymes may lead to elevated concentrations of the respective drugs.

Patient Support and how to buy cardelga online:

Accessing Cerdelga online has been simplified for individuals in the US and Europe. To obtain this medication exclusive to these regions, you can contact the SANSFRO team or other experienced firms specializing in importing medicines. For precise pricing information on Cerdelga in the Indian market, connect with our dedicated Patient Support Team at ‎(+91) 93157 05373 or email help@sansfro.com, ensuring accurate and current cost details.

Conclusion

Cerdelga is a significant advancement for treating Gaucher disease type 1 in adults, specifically those with identified CYP2D6 metabolizer statuses. As a glucosylceramide synthase inhibitor, it addresses the challenges of this genetic disorder. However, careful consideration of patient factors and potential interactions is crucial for optimal use. Ongoing research is enhancing our understanding of Cerdelga’s efficacy, positioning it as a promising addition to Gaucher disease type 1 treatment, with potential for improved patient outcomes.

Reference: 

1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205494orig1s000lbl.pdf
2. https://www.drugs.com/cerdelga.html
3. https://www.fdanews.com/articles/166740-fda-approves-cerdelga-for-type-1-gaucher-disease#:~:text=The%20FDA%20cleared%20Cerdelga%20