SIDE EFFECTS
The following serious adverse reactions are described below and elsewhere in the labeling:
- Peripheral Neuropathy
- Tremor
- Diarrhea and Weight Loss
- Reductions in Platelet Count
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure of 80 patients with type 1 Gaucher disease in two open-label, uncontrolled, monotherapy trials, one open-label, active-controlled trial, and two extensions, who received ZAVESCA at doses ranging from 50 mg to 200 mg three times daily. Patients were aged 18 to 69 years at first treatment. The population was evenly distributed by gender.
The most common serious adverse reaction reported with ZAVESCA treatment in clinical trials was peripheral neuropathy.
The most commonly reported adverse reactions in patients treated with ZAVESCA (occurring in ≥5%) that were considered related to ZAVESCA are shown in Tables 1 and 2.
The most common adverse reactions requiring intervention were diarrhea and tremor.
In two open-label, uncontrolled monotherapy trials, adult type 1 Gaucher disease patients were treated with ZAVESCA at a starting dose of 100 mg three times daily (dose range 100 to 200 mg three times daily) for up to 12 months in 28 patients [Study 1], or at a dose of 50 mg three times daily for up to 6 months in 18 patients [Study 2]. Table 1 below lists adverse reactions that occurred during the trials in ≥5% of patients.
Table 1: Adverse Reactions in≥5%of Patients in Two Open-Label, Uncontrolled Monotherapy Trials of ZAVESCA
| Incidence of adverse reactions | ||
| Study 1 (starting dose 100mgthree times daily) |
Study 2 (50mgthree times daily) |
|
| Patients entered in Study (n) | 28 | 18 |
| Body System-Preferred Term Gastrointestinal System | % of patients reporting | % of patients reporting |
| Diarrhea | 89 | 89 |
| Flatulence | 29 | 44 |
| Abdominal Pain | 18 | 50 |
| Nausea | 14 | 22 |
| Vomiting | 4 | 11 |
| Bloating | 0 | 6 |
| Anorexia | 7 | 0 |
| Dyspepsia | 7 | 0 |
| Epigastric pain not food-related | 0 | 6 |
| Metabolic and Nutritional Disorders | ||
| Weight Decrease | 39 | 67 |
| Central and Peripheral Nervous System | ||
| Headache | 21 | 22 |
| Tremor | 11 | 11 |
| Dizziness | 0 | 11 |
| Leg cramps | 4 | 11 |
| Paresthesia | 7 | 0 |
| Migraine | 0 | 6 |
| Vision Disorders | ||
| Visual Disturbance | 0 | 17 |
| Musculoskeletal Disorders | ||
| Cramps | 0 | 11 |
| Platelet, Bleeding, and Clotting Disorders | ||
| Thrombocytopenia | 7 | 6 |
| Reproductive disorders, female | ||
| Menstrual disorder | 0 | 6 |
In an open-label, active-controlled study, 36 adult type 1 Gaucher disease patients were treated with ZAVESCA, imiglucerase, or ZAVESCA plus imiglucerase [Study 3] for up to 12 months. Table 2 lists adverse reactions that occurred during the trial in ≥5% of patients.
Table 2: Adverse Reactions in≥5% of Patientsin Open-Label Active Controlled Study
| Incidence of adverse reactions | ||
| ZAVESCA alone | Imiglucerase alone | |
| Patients entered in Study (n) | 12 | 12 |
| Body System-PreferredTerm Gastrointestinal System | % of patients reporting | % of patients reporting |
| Diarrhea | 100 | 0 |
| Abdominal Pain | 67 | 0 |
| Flatulence | 50 | 0 |
| Constipation | 8 | 0 |
| Nausea | 8 | 0 |
| Dry Mouth | 8 | 0 |
| Body as a Whole | ||
| Pain | 0 | 8 |
| Generalized weakness | 17 | 0 |
| Abdominaldistension | 8 | 0 |
| Back pain | 8 | 0 |
| Heaviness in limbs | 8 | 0 |
| Metabolic and Nutritional Disorders | ||
| Weight Decrease | 67 | 0 |
| Central and Peripheral Nervous System | ||
| Tremor | 17 | 0 |
| Dizziness | 8 | 0 |
| Leg cramps | 8 | 0 |
| Unsteady gait | 8 | 0 |
| Psychiatric disorders | ||
| Memory loss | 8 | |
SRC: NLM .