Recognizing Signs and Symptoms of Gaucher Disease
Gaucher disease is an inherited, autosomal recessive, lifelong condition marked by extreme diversity in genotype, phenotype, age of onset, and disease severity, as well as an unpredictable, progressive disease course.1,2 Signs, symptoms, and clinical course may differ even among individuals with the same genotype and within the same family.3 Symptoms should not be ignored, as this progressive condition may lead to further medical complications.1
Symptoms Are Diverse, Unpredictable, and Variable1-3
Onset may occur
at any age
Patients may be asymptomatic or present with any number of symptoms
The nature and severity of some symptoms may fluctuate as the disease progresses
Signs and Symptoms
The signs and symptoms of Gaucher disease may not be obvious. The early signs and symptoms of Gaucher disease type 1 tend to reflect the hematologic aspects of the disease, but skeletal manifestations are often present.4
Gaucher disease type 1 often mimics the signs and symptoms of many hematological malignancies (eg, leukemia, lymphoma, or multiple myeloma)1
The most common and frequent symptoms of Gaucher disease include:
- Visceral: splenomegaly and hepatomegaly2
- Hematologic: thrombocytopenia and anemia2,5
- Skeletal: bone pain, Erlenmeyer flask deformity, spontaneous fracture, osteopenia, and osteonecrosis6
Gaucher disease also may display inactive periods interrupted by episodes of acute crises or evidence of disease advancement.1,5 Patients may appear to be asymptomatic, yet harbor mild disease manifestations such as cytopenia, splenomegaly, or osteopenia.4
Gaucher disease is progressive, and delays in diagnosis and/or management may lead to severe and potentially life-threatening complications1,4,7
Bleeding due to thrombocytopenia/coagulopathy
Progressive visceral enlargement
Bone pain, fractures,
avascular necrosis (AVN) (osteonecrosis)
Growth delay in children
Markedly reduced quality of life
Shortened life and increased cancer risk
Early diagnosis and timely treatment are important, as damage caused by Gaucher disease type 1 may be irreversible1,4
Indication and Usage
CERDELGA is indicated for the long-term treatment of adult patients with Gaucher disease type 1 (GD1) who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test.
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).
Important Safety Information
CERDELGA is contraindicated in the following patients based on CYP2D6 metabolizer status due to the risk of cardiac arrhythmias from prolongation of the PR, QTc, and/or QRS cardiac intervals:
- Extensive Metabolizers (EMs) taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor, EMs with moderate or severe hepatic impairment, or EMs with mild hepatic impairment and taking a strong or moderate CYP2D6 inhibitor.
- Intermediate Metabolizers (IMs) taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor, IMs taking a strong CYP3A inhibitor, or IMs with any degree of hepatic impairment.
- Poor Metabolizers (PMs) taking a strong CYP3A inhibitor, or PMs with any degree of hepatic impairment.
WARNINGS AND PRECAUTIONS
CERDELGA is predicted to cause increases in ECG intervals (PR, QTc, and QRS) at substantially elevated plasma concentrations and may increase 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, long QT syndrome, or in combination with Class IA or Class III antiarrhythmic medications.
The most common adverse reactions (≥10%) to CERDELGA include: fatigue, headache, nausea, diarrhea, back pain, pain in extremities, and upper abdominal pain.
Coadministration of CERDELGA with CYP2D6 or CYP3A inhibitors may increase eliglustat concentrations, which may increase the risk of cardiac arrhythmias from prolongations of the PR, QTc, and/or QRS cardiac interval. Use of CERDELGA is contraindicated, to be avoided, or may require dosage adjustment depending on the concomitant drug and CYP2D6 metabolizer status. See section 7 of the full Prescribing Information for more details and other potentially significant drug interactions.
USE IN SPECIFIC POPULATIONS
Available data on the use of CERDELGA in pregnant women is not sufficient to assess drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CERDELGA and any potential adverse effects on the breastfed child from CERDELGA or from the underlying maternal condition.
Use of CERDELGA in patients with renal impairment is based on the patient’s CYP2D6 metabolizer status. Avoid use of CERDELGA in EMs with end-stage renal disease (ESRD), and IMs and PMs with any degree of renal impairment.
Use of CERDELGA is contraindicated or may require dosage adjustment in patients with hepatic impairment based on CYP2D6 metabolizer status, concomitant use of CYP2D6 or CYP3A inhibitors, and degree of hepatic impairment.
Please see accompanying full Prescribing Information.
References: 1. Mistry PK, Sadan S, Yang R, et al. Consequences of diagnostic delays in type 1 Gaucher disease: the need for greater awareness among hematologists-oncologists and an opportunity for early diagnosis and intervention. Am J Hematol. 2007;82(8):697-701. 2. Stirnemann J, Belmatoug N, Camou F, et al. A review of Gaucher disease pathophysiology, clinical presentation and treatments. Int J Mol Sci. 2017;18(2):441. 3. Lachmann RH, Grant IR, Halsall D, et al. Twin pairs showing discordance of phenotype in adult Gaucher's disease. Q J Med. 2004:97(4):199-204. 4. Mistry PK, Cappellini MD, Lukina E, et al. A reappraisal of Gaucher disease-diagnosis and disease management algorithms. Am J Hematol. 2011;86(1):110-115. 5. Mistry PK, Weinthal JA, Weinreb NJ. Disease state awareness in Gaucher disease: a Q&A expert roundtable discussion. Clin Adv Hematol Onc. 2012;10(6 Suppl 8):1-16. 6. Charrow J, Andersson HC, Kaplan P, et al. The Gaucher registry.Demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med. 2000;160(18):2835-2843. 7. Cox TM. Gaucher disease: clinical profile and therapeutic developments. Biologics. 2010:4:299-313.