Rasagiline
Generic: RASAGILINE
Basic Information
Manufacturer
Ascend Laboratories, LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
5dfeec8f-f4f3-4e06-915e-3244467516a6
Indications & Usage
1 INDICATIONS AND USAGE Rasagiline tablets are indicated for the treatment of Parkinson's disease (PD) Rasagiline tablets, a monoamine oxidase (MAO)-B inhibitor (MAOI), is indicated for the treatment of Parkinson’s disease ( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are described in more detail in the Warnings and Precautions section of the label: Hypertension [ see Warnings and Precautions ( 5.1 ) ] Serotonin Syndrome [ see Warnings and Precautions ( 5.2 ) ] Falling Asleep During Activities of Daily Living and Somnolence [ see Warnings and Precautions ( 5.3 ) ] Hypotension / Orthostatic Hypotension [ see Warnings and Precautions ( 5.6) ] Dyskinesia [ see Warnings and Precautions ( 5.7 ) ] Hallucinations / Psychotic-Like Behavior [ see Warnings and Precautions ( 5.8 ) ] Impulse Control /Compulsive Behaviors [ see Warnings and Precautions ( 5.9 ) ] Withdrawal-Emergent Hyperpyrexia and Confusion [ see Warnings and Precautions ( 5.10 ) ] Most common adverse reactions (incidence 3% or greater than placebo): Rasagiline monotherapy: flu syndrome, arthralgia, depression, dyspepsia ( 6.1 ) Rasagiline used as adjunct without levodopa: peripheral edema, fall, arthralgia, cough, and insomnia ( 6.1 ) Rasagiline used as adjunct to levodopa: dyskinesia, accidental injury, weight loss, postural hypotension, vomiting, anorexia, arthralgia, abdominal pain, nausea, constipation, dry mouth, rash, abnormal dreams, fall, and tenosynovitis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) 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 the incidence of adverse reactions in the clinical trials of another drug and may not reflect the rates of adverse reactions observed in practice.
During the clinical development of rasagiline, Parkinson’s disease patients received rasagiline as initial monotherapy (Study 1) and as adjunct therapy (Study 2, Study 3, Study 4).
As the populations in these studies differ, not only in the adjunct use of dopamine agonists or levodopa during rasagiline treatment, but also in the severity and duration of their disease, the adverse reactions are presented separately for each study.
Monotherapy Use of Rasagiline In Study 1, approximately 5% of the 149 patients treated with rasagiline discontinued treatment due to adverse reactions compared to 2% of the 151 patients who received placebo.
The only adverse reaction that led to the discontinuation of more than one patient was hallucinations.
The most commonly observed adverse reactions in Study 1 (incidence in rasagiline -treated patients 3% or greater than the incidence in placebo-treated patients) included flu syndrome, arthralgia, depression, and dyspepsia.
Table 1 lists adverse reactions that occurred in 2% or greater of patients receiving rasagiline as monotherapy and were numerically more frequent than in the placebo group in Study 1.
Table 1: Adverse Reactions* in Study 1 Rasagiline 1 mg (N=149) Placebo (N=151) % of Patients % of Patients Headache 14 12 Arthralgia 7 4 Dyspepsia 7 4 Depression 5 2 Fall 5 3 Flu syndrome 5 1 Conjunctivitis 3 1 Fever 3 1 Gastroenteritis 3 1 Rhinitis 3 1 Arthritis 2 1 Ecchymosis 2 0 Malaise 2 0 Neck Pain 2 0 Paresthesia 2 1 Vertigo 2 1 *Incidence 2% or greater in rasagiline 1 mg group and numerically more frequent than in placebo group There were no significant differences in the safety profile based on age or gender.
Adjunct Use of Rasagiline Rasagiline was studied as an adjunct therapy without levodopa (Study 2), or as an adjunct therapy to levodopa, with some patients also taking dopamine agonists, COMT inhibitors, anticholinergics, or amantadine (Study 3 and Study 4).
In Study 2, approximately 8% of the 162 patients treated with rasagiline discontinued treatment due to adverse reactions compared to 4% of the 164 patients who received placebo.
Adverse reactions that led to the discontinuation of more than one patient were nausea and dizziness.
The most commonly observed adverse reactions in Study 2 (incidence in rasagiline -treated patients 3% or greater than incidence in placebo-treated patients) included peripheral edema, fall, arthralgia, cough, and insomnia.
Table 2 lists adverse reactions that occurred in 2% or greater in patients receiving rasagiline as adjunct therapy without levodopa and numerically more frequent than in the placebo group in Study 2.
Table 2: Adverse Reactions* in Study 2 Rasagiline 1 mg (N=162) Placebo (N=164) % of Patients % of Patients Dizziness 7 6 Peripheral edema 7 4 Headache 6 4 Nausea 6 4 Fall 6 1 Arthralgia 5 2 Back pain 4 3 Cough 4 1 Insomnia 4 1 Upper respiratory tract infection 4 2 Orthostatic hypotension 3 1 *Incidence 2% or greater in rasagiline 1 mg group and numerically more frequent than in placebo group There were no significant differences in the safety profile based on age or gender.
In Study 3, adverse event reporting was considered more reliable than Study 4; therefore, only the adverse event data from Study 3 are presented below.
In Study 3, approximately 9% of the 164 patients treated with rasagiline 0.5 mg/day and 7% of the 149 patients treated with rasagiline 1 mg/day discontinued treatment due to adverse reactions, compared to 6% of the 159 patients who received placebo.
The adverse reactions that led to discontinuation of more than one rasagiline -treated patient were diarrhea, weight loss, hallucination, and rash.
The most commonly observed adverse reactions in Study 3 (incidence in rasagiline -treated patients 3% or greater than the incidence in placebo-treated patients) included dyskinesia, accidental injury, weight loss, postural hypotension, vomiting, anorexia, arthralgia, abdominal pain, nausea, constipation, dry mouth, rash, abnormal dreams, fall and tenosynovitis.
Table 3 lists adverse reactions that occurred in 2% or greater of patients treated with rasagiline 1 mg/day and that were numerically more frequent than the placebo group in Study 3.
Table 3: Adverse Reactions* in Study 3 Rasagiline 1 mg (N=149) Rasagiline 0.5 mg (N=164) Placebo (N=159) % of patients % of patients % of patients Dyskinesia 18 18 10 Accidental injury 12 8 5 Nausea 12 10 8 Headache 11 8 10 Fall 11 12 8 Weight loss 9 2 3 Constipation 9 4 5 Postural hypotension 9 6 3 Arthralgia 8 6 4 Vomiting 7 4 1 Dry mouth 6 2 3 Rash 6 3 3 Somnolence 6 4 4 Abdominal pain 5 2 1 Anorexia 5 2 1 Diarrhea 5 7 4 Ecchymosis 5 2 3 Dyspepsia 5 4 4 Paresthesia 5 2 3 Abnormal dreams 4 1 1 Hallucinations 4 5 3 Ataxia 3 6 1 Dyspnea 3 5 2 Infection 3 2 2 Neck pain 3 1 1 Sweating 3 2 1 Tenosynovitis 3 1 0 Dystonia 3 2 1 Gingivitis 2 1 1 Hemorrhage 2 1 1 Hernia 2 1 1 Myasthenia 2 2 1 *Incidence 2% or greater in rasagiline 1 mg group and numerically more frequent than in placebo group Several of the more common adverse reactions seemed dose-related, including weight loss, postural hypotension, and dry mouth.
There were no significant differences in the safety profile based on age or gender.
During all Parkinson’s disease phase 2/3 clinical trials, the long-term safety profile was similar to that observed with shorter duration exposure.
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of rasagiline.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Skin and Subcutaneous Tissue Disorders: Melanoma
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 the incidence of adverse reactions in the clinical trials of another drug and may not reflect the rates of adverse reactions observed in practice.
During the clinical development of rasagiline, Parkinson’s disease patients received rasagiline as initial monotherapy (Study 1) and as adjunct therapy (Study 2, Study 3, Study 4).
As the populations in these studies differ, not only in the adjunct use of dopamine agonists or levodopa during rasagiline treatment, but also in the severity and duration of their disease, the adverse reactions are presented separately for each study.
Monotherapy Use of Rasagiline In Study 1, approximately 5% of the 149 patients treated with rasagiline discontinued treatment due to adverse reactions compared to 2% of the 151 patients who received placebo.
The only adverse reaction that led to the discontinuation of more than one patient was hallucinations.
The most commonly observed adverse reactions in Study 1 (incidence in rasagiline -treated patients 3% or greater than the incidence in placebo-treated patients) included flu syndrome, arthralgia, depression, and dyspepsia.
Table 1 lists adverse reactions that occurred in 2% or greater of patients receiving rasagiline as monotherapy and were numerically more frequent than in the placebo group in Study 1.
Table 1: Adverse Reactions* in Study 1 Rasagiline 1 mg (N=149) Placebo (N=151) % of Patients % of Patients Headache 14 12 Arthralgia 7 4 Dyspepsia 7 4 Depression 5 2 Fall 5 3 Flu syndrome 5 1 Conjunctivitis 3 1 Fever 3 1 Gastroenteritis 3 1 Rhinitis 3 1 Arthritis 2 1 Ecchymosis 2 0 Malaise 2 0 Neck Pain 2 0 Paresthesia 2 1 Vertigo 2 1 *Incidence 2% or greater in rasagiline 1 mg group and numerically more frequent than in placebo group There were no significant differences in the safety profile based on age or gender.
Adjunct Use of Rasagiline Rasagiline was studied as an adjunct therapy without levodopa (Study 2), or as an adjunct therapy to levodopa, with some patients also taking dopamine agonists, COMT inhibitors, anticholinergics, or amantadine (Study 3 and Study 4).
In Study 2, approximately 8% of the 162 patients treated with rasagiline discontinued treatment due to adverse reactions compared to 4% of the 164 patients who received placebo.
Adverse reactions that led to the discontinuation of more than one patient were nausea and dizziness.
The most commonly observed adverse reactions in Study 2 (incidence in rasagiline -treated patients 3% or greater than incidence in placebo-treated patients) included peripheral edema, fall, arthralgia, cough, and insomnia.
Table 2 lists adverse reactions that occurred in 2% or greater in patients receiving rasagiline as adjunct therapy without levodopa and numerically more frequent than in the placebo group in Study 2.
Table 2: Adverse Reactions* in Study 2 Rasagiline 1 mg (N=162) Placebo (N=164) % of Patients % of Patients Dizziness 7 6 Peripheral edema 7 4 Headache 6 4 Nausea 6 4 Fall 6 1 Arthralgia 5 2 Back pain 4 3 Cough 4 1 Insomnia 4 1 Upper respiratory tract infection 4 2 Orthostatic hypotension 3 1 *Incidence 2% or greater in rasagiline 1 mg group and numerically more frequent than in placebo group There were no significant differences in the safety profile based on age or gender.
In Study 3, adverse event reporting was considered more reliable than Study 4; therefore, only the adverse event data from Study 3 are presented below.
In Study 3, approximately 9% of the 164 patients treated with rasagiline 0.5 mg/day and 7% of the 149 patients treated with rasagiline 1 mg/day discontinued treatment due to adverse reactions, compared to 6% of the 159 patients who received placebo.
The adverse reactions that led to discontinuation of more than one rasagiline -treated patient were diarrhea, weight loss, hallucination, and rash.
The most commonly observed adverse reactions in Study 3 (incidence in rasagiline -treated patients 3% or greater than the incidence in placebo-treated patients) included dyskinesia, accidental injury, weight loss, postural hypotension, vomiting, anorexia, arthralgia, abdominal pain, nausea, constipation, dry mouth, rash, abnormal dreams, fall and tenosynovitis.
Table 3 lists adverse reactions that occurred in 2% or greater of patients treated with rasagiline 1 mg/day and that were numerically more frequent than the placebo group in Study 3.
Table 3: Adverse Reactions* in Study 3 Rasagiline 1 mg (N=149) Rasagiline 0.5 mg (N=164) Placebo (N=159) % of patients % of patients % of patients Dyskinesia 18 18 10 Accidental injury 12 8 5 Nausea 12 10 8 Headache 11 8 10 Fall 11 12 8 Weight loss 9 2 3 Constipation 9 4 5 Postural hypotension 9 6 3 Arthralgia 8 6 4 Vomiting 7 4 1 Dry mouth 6 2 3 Rash 6 3 3 Somnolence 6 4 4 Abdominal pain 5 2 1 Anorexia 5 2 1 Diarrhea 5 7 4 Ecchymosis 5 2 3 Dyspepsia 5 4 4 Paresthesia 5 2 3 Abnormal dreams 4 1 1 Hallucinations 4 5 3 Ataxia 3 6 1 Dyspnea 3 5 2 Infection 3 2 2 Neck pain 3 1 1 Sweating 3 2 1 Tenosynovitis 3 1 0 Dystonia 3 2 1 Gingivitis 2 1 1 Hemorrhage 2 1 1 Hernia 2 1 1 Myasthenia 2 2 1 *Incidence 2% or greater in rasagiline 1 mg group and numerically more frequent than in placebo group Several of the more common adverse reactions seemed dose-related, including weight loss, postural hypotension, and dry mouth.
There were no significant differences in the safety profile based on age or gender.
During all Parkinson’s disease phase 2/3 clinical trials, the long-term safety profile was similar to that observed with shorter duration exposure.
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of rasagiline.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Skin and Subcutaneous Tissue Disorders: Melanoma