For further medical information on Actelion treatments, please contact our Medical Information Department.
Patients should always talk with their healthcare team first if there are any questions about their individual treatment.
IMPORTANT SAFETY INFORMATION
WARNING AND PRECAUTIONS
In clinical trials, cases of peripheral neuropathy have been reported in 3% of Gaucher's patients treated with ZAVESCA.
- Patients should undergo baseline and repeat neurological evaluations at approximately 6-month intervals.
- Patients who develop symptoms of peripheral neuropathy such as pain, weakness, numbness and tingling should have a careful re-assessment of the risk/benefit of ZAVESCA therapy and cessation of treatment may be considered.
Approximately 30% of patients taking ZAVESCA have reported tremor or exacerbation of existing tremor. These tremors were described as an exaggerated physiological tremor of the hands.
- Tremor usually began within the first month of therapy and in many cases resolved within 1 to 3 months.
- Reduce dose to ameliorate tremor or discontinue treatment if tremor does not resolve within days of dose reduction.
Diarrhea and Weight Loss
- Diarrhea and weight loss were common in clinical studies of patients treated with ZAVESCA, occurring in approximately 85% and up to 65% of treated patients, respectively. It is unclear if weight loss results from the diarrhea and associated gastrointestinal complaints, a decrease in food intake, or a combination of these or other factors.
- The incidence of weight loss was most evident in the first 12 months of treatment.
- Diarrhea decreased over time with continued ZAVESCA treatment, and may respond to individualized diet modification (e.g., reduction of sucrose, lactose and other carbohydrate intake), to taking ZAVESCA between meals, and/or to anti-diarrheal medications, most commonly loperamide. Patients may be instructed to avoid high carbohydrate content foods during treatment with ZAVESCA if they present with diarrhea.
- Evaluate for underlying gastrointestinal disease in patients who do not respond to usual interventions (e.g. diet modification). The safety of treatment with ZAVESCA has not been evaluated in patients with significant gastrointestinal disease, such as inflammatory bowel disease, and continued treatment of these patients with ZAVESCA should occur only after consideration of the risks and benefits of continued treatment.
Reductions in Platelet Count
- Monitoring of platelet counts is recommended in patients with type 1 Gaucher disease.
- Mild reductions in platelet counts without association with bleeding were observed in patients with type 1 Gaucher disease, both in the clinical trials and in patients with type 1 Gaucher disease who were switched from enzyme replacement therapy (ERT) to ZAVESCA.
The most common serious adverse reaction reported with ZAVESCA treatment in clinical trials was peripheral neuropathy.
The most common adverse reactions requiring intervention were diarrhea and tremor.
Adverse reactions in ≥5% of patients in two open-label, uncontrolled monotherapy trials of ZAVESCA and in an open-label active controlled study (Study 1, Study 2, Study 3):
DOSAGE AND ADMINISTRATION
The recommended dose for the treatment of adult patients with type 1 Gaucher disease is one 100 mg capsule administered orally three times a day at regular intervals. It may be necessary to reduce the dose to one 100 mg capsule once or twice a day in some patients for adverse effects, such as diarrhea or tremor.
Patients with Renal Insufficiency
- In patients with mild renal impairment (adjusted creatinine clearance 50-70 mL/min/1.73 m2), ZAVESCA administration should commence at a dose of 100 mg twice per day.
- In patients with moderate renal impairment (adjusted creatinine clearance of 30-50 mL/min/1.73 m2), ZAVESCA administration should commence at a dose of one 100 mg capsule per day.
- Use of ZAVESCA in patients with severe renal impairment (creatinine clearance < 30 mL/min/1.73 m2) is not recommended.
Co-administration of ZAVESCA and imiglucerase may lead to increased clearance of imiglucerase.
USE IN SPECIFIC POPULATIONS
Based on animal data, ZAVESCA may cause fetal harm.
Discontinue drug or nursing based on importance of the drug to the mother.
Please see accompanying full Prescribing Information.