MIGLUSTAT
Generic: MIGLUSTAT
Basic Information
Manufacturer
ANI Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
d746749d-de15-4225-b806-59b0765d25ae
Indications & Usage
1 INDICATIONS AND USAGE Miglustat is a glucosylceramide synthase inhibitor indicated as monotherapy for treatment of adult patients with mild/moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option ( 1.1 ).
1.1 Type 1 Gaucher Disease Miglustat is indicated as monotherapy for the treatment of adult patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g.
due to allergy, hypersensitivity, or poor venous access).
1.1 Type 1 Gaucher Disease Miglustat is indicated as monotherapy for the treatment of adult patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g.
due to allergy, hypersensitivity, or poor venous access).
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: • Peripheral Neuropathy [see Warnings and Precautions ( 5.1 )] • Tremor [see Warnings and Precautions ( 5.2 )] • Diarrhea and Weight Loss [see Warnings and Precautions ( 5.3 )] • Reductions in Platelet Count [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (incidence ≥5%) are diarrhea, weight loss, stomach pain, gas, nausea and vomiting, headache including migraine, tremor, leg cramps, dizziness, weakness, vision problems, thrombocytopenia, muscle cramps, back pain, constipation, dry mouth, heaviness in arms and legs, memory loss, unsteady walking, anorexia, indigestion, paresthesia, stomach bloating, stomach pain not related to food, and menstrual changes ( 6.1 ).
To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc.
at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 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 miglustat capsules 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 miglustat capsule treatment in clinical trials was peripheral neuropathy [see Warnings and Precautions ( 5.1 )] .
The most commonly reported adverse reactions in patients treated with miglustat capsules (occurring in ≥5%) that were considered related to miglustat are shown in Tables 1 and 2 [see Warnings and Precautions ( 5.2 , 5.3 )] .
The most common adverse reactions requiring intervention were diarrhea and tremor [see Warnings and Precautions ( 5.2 , 5.3 )] .
In two open-label, uncontrolled monotherapy trials, adult type 1 Gaucher disease patients were treated with miglustat capsules 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 Miglustat Capsules Incidence of adverse reactions Study 1 (starting dose 100 mg three times daily) Study 2 (50 mg three times daily) Patients entered in Study (n) 28 18 Body System - Preferred Term % of patients reporting % of patients reporting Gastrointestinal System 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 miglustat, imiglucerase, or miglustat 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 Patients in Open-Label Active Controlled Study Incidence of adverse reactions Miglustat Capsules alone Imiglucerase alone Patients entered in Study (n) 12 12 Body System - Preferred Term % of patients reporting % of patients reporting Gastrointestinal System 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 Abdominal distension 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 0
To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc.
at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 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 miglustat capsules 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 miglustat capsule treatment in clinical trials was peripheral neuropathy [see Warnings and Precautions ( 5.1 )] .
The most commonly reported adverse reactions in patients treated with miglustat capsules (occurring in ≥5%) that were considered related to miglustat are shown in Tables 1 and 2 [see Warnings and Precautions ( 5.2 , 5.3 )] .
The most common adverse reactions requiring intervention were diarrhea and tremor [see Warnings and Precautions ( 5.2 , 5.3 )] .
In two open-label, uncontrolled monotherapy trials, adult type 1 Gaucher disease patients were treated with miglustat capsules 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 Miglustat Capsules Incidence of adverse reactions Study 1 (starting dose 100 mg three times daily) Study 2 (50 mg three times daily) Patients entered in Study (n) 28 18 Body System - Preferred Term % of patients reporting % of patients reporting Gastrointestinal System 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 miglustat, imiglucerase, or miglustat 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 Patients in Open-Label Active Controlled Study Incidence of adverse reactions Miglustat Capsules alone Imiglucerase alone Patients entered in Study (n) 12 12 Body System - Preferred Term % of patients reporting % of patients reporting Gastrointestinal System 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 Abdominal distension 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 0