Rasagiline mesylate

Tablet · Oral

Prescription (Rx) Monoamine Oxidase Inhibitor

Uses

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

Dosage and administration

Monotherapy: Rasagiline tablets 1 mg once daily ( 2.1 ) As adjunct without levodopa: Rasagiline tablets 1 mg once daily ( 2.1 ) As adjunct to levodopa: Rasagiline tablets 0.5 mg once daily. Increase dose to 1 mg daily as needed for sufficient clinical response ( 2.1 ) Patients taking ciprofloxacin or other CYP1A2 inhibitors: Rasagiline tablets 0.5 mg once daily ( 2.2, 5.4 ) Patients with mild hepatic impairment: Rasagiline tablets 0.5 mg once daily. Rasagiline tablets should not be used in patients with moderate or severe hepatic impairment ( 2.3 , 5.5 ) 2.1 General Dosing Recommendations When rasagiline tablets are prescribed as monotherapy or as adjunct therapy in patients not taking levodopa, patients may start rasagiline tablets at the recommended dose of 1 mg administered orally once daily. In patients taking levodopa, with or without other PD drugs (e.g., dopamine agonist, amantadine, anticholinergics), the recommended initial dose of rasagiline tablets is 0.5 mg once daily. If the patient tolerates the daily 0.5 mg dose, but a sufficient clinical response is not achieved, the dose may be increased to 1 mg once daily. When rasagiline tablets are used in combination with levodopa, a reduction of the levodopa dose may be considered, based upon individual response. The recommended doses of rasagiline tablets should not be exceeded because of risk of hypertension [see Warnings and Precautions ( 5.1 )] . 2.2 Patients Taking Ciprofloxacin or Other CYP1A2 Inhibitors Patients taking concomitant ciprofloxacin or other CYP1A2 inhibitors should not exceed a dose of rasagiline tablets 0.5 mg once daily [see Warnings and Precautions ( 5.4 ), Drug Interactions ( 7.6 ), and Clinical Pharmacology ( 12.3 )] . 2.3 Patients with Hepatic Impairment Patients with mild hepatic impairment should not exceed a dose of rasagiline tablets 0.5 mg once daily. Rasagiline tablets should not be used in patients with moderate or severe hepatic impairment [see Warnings and Precautions ( 5.5 ), Use in Specific Populations ( 8.6 ), and Clinical Pharmacology ( 12.3 )] .

Dosage forms and strengths

Rasagiline tablets 0.5 mg: White to off-white, round, flat, beveled tablets, debossed with “31” on one side and “I” on the other side. Rasagiline tablets 1 mg: White to off-white, round, flat, beveled tablets, debossed with “32” on one side and “I” on the other side. Rasagiline tablets 0.5 mg tablets ( 3 ) Rasagiline tablets 1 mg tablets ( 3 )

Contraindications

Rasagiline tablets are contraindicated for use with meperidine, tramadol, methadone, propoxyphene and MAO inhibitors (MAOIs), including other selective MAO-B inhibitors, because of risk of serotonin syndrome [See Warnings and Precautions ( 5.2 )]. At least 14 days should elapse between discontinuation of rasagiline tablets and initiation of treatment with these medications. Rasagiline tablets are contraindicated for use with St. John’s wort and with cyclobenzaprine. Rasagiline tablets are contraindicated for use with dextromethorphan because of risk of episode of psychosis or bizarre behavior. Concomitant use of meperidine, tramadol, methadone, propoxyphene dextromethorphan, St. John’s wort, cyclobenzaprine, or another (selective or non-selective) MAO inhibitor

Warnings and precautions

May cause hypertension (including severe hypertensive syndromes) at recommended doses ( 5.1 ) May cause serotonin syndrome when used with antidepressants ( 5.2 ) May cause falling asleep during activities of daily living, daytime drowsiness, and somnolence ( 5.3 ) May cause hypotension, especially orthostatic ( 5.6 ) May cause or exacerbate dyskinesia. Decreasing the levodopa dose may lessen or eliminate this side effect ( 5.7 ) May cause hallucinations and psychotic-like behavior ( 5.8 ) May cause impulse control/compulsive behaviors ( 5.9 ) May cause withdrawal-emergent hyperpyrexia and confusion ( 5.10 ) 5.1 Hypertension Exacerbation of hypertension may occur during treatment with rasagiline. Medication adjustment may be necessary if elevation of blood pressure is sustained. Monitor patients for new onset hypertension or hypertension that is not adequately controlled after starting rasagiline. In Study 3, rasagiline (1 mg/day) given in conjunction with levodopa, produced an increased incidence of significant blood pressure elevation (systolic > 180 or diastolic > 100 mm Hg) of 4% compared to 3% for placebo [see Adverse Reactions ( 6.1 )]. When used as an adjunct to levodopa (Studies 3 and 4), the risk for developing post-treatment high blood pressure (e.g., systolic > 180 or diastolic >100 mm Hg) combined with a significant increase from baseline (e.g., systolic > 30 or diastolic > 20 mm Hg) was higher for rasagiline (2%) compared to placebo (1%). Dietary tyramine restriction is not required during treatment with recommended doses of rasagiline. However, certain foods that may contain very high amounts (i.e., more than 150 mg) of tyramine that could potentially cause severe hypertension because of tyramine interaction (including various clinical syndromes referred to as hypertensive urgency, crisis, or emergency) in patients taking rasagiline, even at the recommended doses, due to increased sensitivity to tyramine. Patients should be advised to avoid foods containing a very large amount of tyramine while taking recommended doses of rasagiline because of the potential for large increases in blood pressure including clinical syndromes referred to as hypertensive urgency, crisis, or emergency. Rasagiline is a selective inhibitor of MAO-B at the recommended doses of 0.5 or 1 mg daily. Selectivity for inhibiting MAO-B diminishes in a dose-related manner as the dose is progressively increased above the recommended daily doses. 5.2 Serotonin Syndrome Serotonin syndrome has been reported with concomitant use of an antidepressant (e.g., selective serotonin reuptake inhibitors-SSRIs, serotonin-norepinephrine reuptake inhibitors-SNRIs, tricyclic antidepressants, tetracyclic antidepressants, triazolopyridine antidepressants) and a nonselective MAOI (e.g., phenelzine, tranylcypromine) or selective MAO-B inhibitors, such as selegiline (Eldepryl) and rasagiline (rasagiline tablets). Serotonin syndrome has also been reported with concomitant use of rasagiline with meperidine, tramadol, methadone, or propoxyphene. Rasagiline is contraindicated for use with meperidine, tramadol, methadone, propoxyphene, and MAO inhibitors (MAOIs), including other selective MAO-B inhibitors [see Contraindications ( 4 ) and Drug Interactions ( 7.1 , 7.2 , 7.3 )] . In the postmarketing period, potentially life-threatening serotonin syndrome has been reported in patients treated with antidepressants concomitantly with rasagiline. Concomitant use of rasagiline with one of many classes of antidepressants (e.g., SSRIs, SNRIs, triazolopyridine, tricyclic or tetracyclic antidepressants) is not recommended [see Drug Interactions ( 7.5 )]. The symptoms of serotonin syndrome have included behavioral and cognitive/mental status changes (e.g., confusion, hypomania, hallucinations, agitation, delirium, headache, and coma), autonomic effects (e.g., syncope, shivering, sweating, high fever/hyperthermia, hypertension, tachycardia, nausea, diarrhea), and somatic effects (e.g., muscular rigidity, myoclonus, muscle twitching, hyperreflexia manifested by clonus, and tremor). Serotonin syndrome can result in death. Rasagiline clinical trials did not allow concomitant use of fluoxetine or fluvoxamine with rasagiline, and the potential drug interaction between rasagiline and antidepressants has not been studied systematically. Although a small number of rasagiline-treated patients were concomitantly exposed to antidepressants (tricyclics n=115; SSRIs n=141), the exposure, both in dose and number of subjects, was not adequate to rule out the possibility of an untoward reaction from combining these agents. At least 14 days should elapse between discontinuation of rasagiline and initiation of treatment with a SSRI, SNRI, tricyclic, tetracyclic, or triazolopyridine antidepressant. Because of the long half-lives of certain antidepressants (e.g., fluoxetine and its active metabolite), at least five weeks (perhaps longer, especially if fluoxetine has been prescribed chronically and/or at higher doses) should elapse between discontinuation of fluoxetine and initiation of rasagiline [see Drug Interactions ( 7.5 )]. 5.3 Falling Asleep During Activities of Daily Living and Somnolence It has been reported that falling asleep while engaged in activities of daily living always occurs in a setting of preexisting somnolence, although patients may not give such a history. For this reason, prescribers should monitor patients for drowsiness or sleepiness, because some of the events occur well after initiation of treatment with dopaminergic medication. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Cases of patients treated with rasagiline and other dopaminergic medications have reported falling asleep while engaged in activities of daily living including the operation of motor vehicles, which sometimes resulted in accidents.

Side effects

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 tablets monotherapy: flu syndrome, arthralgia, depression, dyspepsia ( 6.1 ) Rasagiline tablets used as adjunct without levodopa: peripheral edema, fall, arthralgia, cough, and insomnia ( 6.1 ) Rasagiline tablets 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 at 1-833-856-0880 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.

Drug interactions

Meperidine: Risk of serotonin syndrome ( 4 , 7.1 ) Dextromethorphan: Risk of psychosis or bizarre behavior ( 4 , 7.2 ) MAO inhibitors: Risk of non-selective MAO inhibition and hypertensive crisis ( 4 , 7.3 ) 7.1 Meperidine Serious, sometimes fatal reactions have been precipitated with concomitant use of meperidine (e.g., Demerol and other tradenames) and MAO inhibitors including selective MAO-B inhibitors [see Contraindications ( 4 )]. 7.2 Dextromethorphan The concomitant use of rasagiline and dextromethorphan was not allowed in clinical studies. The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior. Therefore, in view of rasagiline's MAO inhibitory activity, dextromethorphan is contraindicated for use with rasagiline [see Contraindications ( 4 )]. 7.3 MAO Inhibitors Rasagiline is contraindicated for use with other MAO inhibitors because of the increased risk of nonselective MAO inhibition that may lead to a hypertensive crisis [see Contraindications ( 4 )] . 7.4 Sympathomimetic Medications The concomitant use of rasagiline and sympathomimetic medications was not allowed in clinical studies. Severe hypertensive reactions have followed the administration of sympathomimetics and nonselective MAO inhibitors. Hypertensive crisis has been reported in patients taking the recommended dose of rasagiline and sympathomimetic medications. Severe hypertension has been reported in patients taking the recommended dose of rasagiline and ophthalmic drops containing sympathomimetic medications. Because rasagiline are a selective MAOI, hypertensive reactions are not ordinarily expected with the concomitant use of sympathomimetic medications. Nevertheless, caution should be exercised when concomitantly using recommended doses of rasagiline with any sympathomimetic medications including nasal, oral, and ophthalmic decongestants and cold remedies. 7.5 Antidepressants Concomitant use of rasagiline with one of many classes of antidepressants (e.g., SSRIs, SNRIs, triazolopyridine, tricyclic or tetracyclic antidepressants) is not recommended [see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 )]. Concomitant use of rasagiline tablets and MAO inhibitors is contraindicated [see Contraindications ( 4 )] . 7.6 Ciprofloxacin or Other CYP1A2 Inhibitors Rasagiline plasma concentrations may increase up to 2 fold in patients using concomitant ciprofloxacin and other CYP1A2 inhibitors. This could result in increased adverse events. Patients taking concomitant ciprofloxacin or other CYP1A2 inhibitors should not exceed a dose of rasagiline 0.5 mg once daily [see Warnings and Precautions ( 5.4 ) and Clinical Pharmacology ( 12.3 )]. 7.7 Tyramine/Rasagiline Interaction MAO in the gastrointestinal tract and liver (primarily type A) provides protection from exogenous amines (e.g., tyramine) that have the capacity, if absorbed intact, to cause a tyramine reaction with hypertension including clinical syndromes referred to as hypertensive urgency, crisis, or emergency. Foods and medications containing large amounts of exogenous amines (e.g., from fermented cheese, herring, over-the-counter cough/cold medications) may cause release of norepinephrine resulting in a rise in systemic blood pressure. Results of a special tyramine challenge study indicate that rasagiline is selective for MAO-B at recommended doses and can be used without dietary tyramine restriction. However, certain foods may contain very high amounts (i.e., 150 mg or greater) of tyramine and could potentially cause a hypertensive reaction in individual patients taking rasagiline due to increased sensitivity to tyramine. Selectivity for inhibiting MAO-B diminishes in a dose-related manner as the dose is progressively increased above the recommended daily doses. There were no cases of hypertensive crisis in the clinical development program associated with 1 mg daily rasagiline treatment, in which most patients did not follow dietary tyramine restriction. There have been postmarketing reports of patients who experienced significantly elevated blood pressure (including rare cases of hypertensive crisis) after ingestion of unknown amounts of tyramine-rich foods while taking recommended doses of rasagiline. Patients should be advised to avoid foods containing a very large amount of tyramine while taking recommended doses of rasagiline [see Warnings and Precautions ( 5.1 )]. 7.8 Dopaminergic Antagonists It is possible that dopamine antagonists, such as antipsychotics or metoclopramide, could diminish the effectiveness of rasagiline.

Use in specific populations

Pregnancy: Based on animal data, may cause fetal harm. ( 8.1 ) See 17 for PATIENT COUNSELING INFORMATION 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of rasagiline in pregnant women. In animal studies, oral administration of rasagiline to rats during gestation and lactation resulted in decreased survival and reduced body weight in the offspring at doses similar to those used clinically. When administrated to pregnant animals in combination with levodopa/carbidopa, there were increased incidences of fetal skeletal variations in rats and increases in embryofetal death and cardiovascular abnormalities in rabbits [see Data] . In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risks of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data In a combined mating/fertility and embryofetal development study in pregnant rats, no effect on embryofetal development was observed at oral doses up to 3 mg/kg/day (approximately 30 times the plasma exposure (AUC) in humans at the maximum recommended human dose [MRHD, 1 mg/day]). In pregnant rabbits administered rasagiline throughout the period of organogenesis at oral doses of up to 36 mg/kg/day, no developmental toxicity was observed. At the highest dose tested, the plasma AUC was approximately 800 times that in humans at the MRHD. In pregnant rats administered rasagiline (0, 0.1, 0.3, 1 mg/kg/day) orally during gestation and lactation, offspring survival was decreased and offspring body weight was reduced at 0.3 mg/kg/day and 1 mg/kg/day (10 and 16 times the plasma AUC in humans at the MRHD). The no-effect dose (0.1 mg/kg) for adverse development effect is similar to the MRHD on a body surface area (mg/m 2 ) basis. The effect of rasagiline on physical and behavioral development was not adequately assessed in this study. Rasagiline may be given as an adjunct therapy to levodopa/carbidopa treatment. In pregnant rats administered rasagiline (0, 0.1, 0.3, 1 mg/kg/day) and levodopa/carbidopa (80/20 mg/kg/day) (alone and in combination) orally throughout the period of organogenesis, there was an increased incidence of fetal skeletal variations in fetuses from rats treated with rasagiline in combination with levodopa/carbidopa at 1/80/20 mg/kg/day (approximately 8 times the rasagiline plasma AUC in humans at the MRHD and similar to the MRHD of levodopa/carbidopa [800/200 mg/day] on a mg/m 2 basis). In pregnant rabbits dosed orally throughout the period of organogenesis with rasagiline alone (3 mg/kg) or in combination with levodopa/carbidopa (rasagiline: 0.1, 0.6, 1.2 mg/kg, levodopa/carbidopa: 80/20 mg/kg/day), an increase in embryofetal death was noted at rasagiline doses of 0.6 and 1.2 mg/kg/day when administered in combination with levodopa/carbidopa (approximately 7 and 13 times, respectively, the rasagiline plasma AUC in humans at the MRHD). There was an increase in cardiovascular abnormalities with levodopa/carbidopa alone (similar to the MRHD on a mg/m 2 basis) and to a greater extent when rasagiline (at all doses; 1-13 times the rasagiline plasma AUC in humans at the MRHD) was administered in combination with levodopa/carbidopa. 8.2 Lactation Risk Summary There are no data on the presence of rasagiline in human milk or the effects on the breastfed infant. In rats, rasagiline was shown to inhibit prolactin secretion. The clinical relevance in humans is unknown, and there are no data on the effects of rasagiline on prolactin secretion or milk production in humans. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for rasagiline and any potential adverse effects on the breastfed infant from rasagiline or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Approximately half of patients in clinical trials were 65 years and over. There were no significant differences in the safety profile of the geriatric and nongeriatric patients. 8.6 Hepatic Impairment Rasagiline plasma concentration may be increased in patients with mild (up to 2 fold, Child-Pugh score 5-6), moderate (up to 7 fold, Child-Pugh score 7-9), and severe (Child-Pugh score 10-15) hepatic impairment. Patients with mild hepatic impairment should not exceed a dose of 0.5 mg/day. Rasagiline should not be used in patients with moderate or severe hepatic impairment [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.5 ) and Clinical Pharmacology ( 12.3 )] . 8.7 Renal Impairment Dose adjustment of rasagiline is not required for patients with mild or moderate renal impairment because rasagiline plasma concentrations are not increased in patients with moderate renal impairment. Rasagiline has not been studied in patients with severe renal impairment [see Clinical Pharmacology ( 12.3 )] .

Pregnancy

8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of rasagiline in pregnant women. In animal studies, oral administration of rasagiline to rats during gestation and lactation resulted in decreased survival and reduced body weight in the offspring at doses similar to those used clinically. When administrated to pregnant animals in combination with levodopa/carbidopa, there were increased incidences of fetal skeletal variations in rats and increases in embryofetal death and cardiovascular abnormalities in rabbits [see Data] . In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risks of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data In a combined mating/fertility and embryofetal development study in pregnant rats, no effect on embryofetal development was observed at oral doses up to 3 mg/kg/day (approximately 30 times the plasma exposure (AUC) in humans at the maximum recommended human dose [MRHD, 1 mg/day]). In pregnant rabbits administered rasagiline throughout the period of organogenesis at oral doses of up to 36 mg/kg/day, no developmental toxicity was observed. At the highest dose tested, the plasma AUC was approximately 800 times that in humans at the MRHD. In pregnant rats administered rasagiline (0, 0.1, 0.3, 1 mg/kg/day) orally during gestation and lactation, offspring survival was decreased and offspring body weight was reduced at 0.3 mg/kg/day and 1 mg/kg/day (10 and 16 times the plasma AUC in humans at the MRHD). The no-effect dose (0.1 mg/kg) for adverse development effect is similar to the MRHD on a body surface area (mg/m 2 ) basis. The effect of rasagiline on physical and behavioral development was not adequately assessed in this study. Rasagiline may be given as an adjunct therapy to levodopa/carbidopa treatment. In pregnant rats administered rasagiline (0, 0.1, 0.3, 1 mg/kg/day) and levodopa/carbidopa (80/20 mg/kg/day) (alone and in combination) orally throughout the period of organogenesis, there was an increased incidence of fetal skeletal variations in fetuses from rats treated with rasagiline in combination with levodopa/carbidopa at 1/80/20 mg/kg/day (approximately 8 times the rasagiline plasma AUC in humans at the MRHD and similar to the MRHD of levodopa/carbidopa [800/200 mg/day] on a mg/m 2 basis). In pregnant rabbits dosed orally throughout the period of organogenesis with rasagiline alone (3 mg/kg) or in combination with levodopa/carbidopa (rasagiline: 0.1, 0.6, 1.2 mg/kg, levodopa/carbidopa: 80/20 mg/kg/day), an increase in embryofetal death was noted at rasagiline doses of 0.6 and 1.2 mg/kg/day when administered in combination with levodopa/carbidopa (approximately 7 and 13 times, respectively, the rasagiline plasma AUC in humans at the MRHD). There was an increase in cardiovascular abnormalities with levodopa/carbidopa alone (similar to the MRHD on a mg/m 2 basis) and to a greater extent when rasagiline (at all doses; 1-13 times the rasagiline plasma AUC in humans at the MRHD) was administered in combination with levodopa/carbidopa.

Pediatric use

8.4 Pediatric Use The safety and effectiveness in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Approximately half of patients in clinical trials were 65 years and over. There were no significant differences in the safety profile of the geriatric and nongeriatric patients.

Overdosage

In a dose escalation study in patients on chronic levodopa therapy treated with 10 mg of rasagiline there were three reports of cardiovascular side effects (including hypertension and postural hypotension) which resolved following treatment discontinuation. Although no cases of overdose have been observed with rasagiline during the clinical development program, the following description of presenting symptoms and clinical course is based upon overdose descriptions of nonselective MAO inhibitors. The signs and symptoms of nonselective MAOI overdose may not appear immediately. Delays of up to 12 hours after ingestion of drug and the appearance of signs may occur. The peak intensity of the syndrome may not be reached until for a day following the overdose. Death has been reported following overdose; therefore, immediate hospitalization, with continuous patient observation and monitoring for at least two days following the ingestion of such drugs in overdose, is strongly recommended. The severity of the clinical signs and symptoms of MAOI overdose varies and may be related to the amount of drug consumed. The central nervous and cardiovascular systems are prominently involved. Signs and symptoms of MAOI overdose may include: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions, and coma; rapid and irregular pulse, hypertension, hypotension and vascular collapse; precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin. There is no specific antidote for rasagiline overdose. The following suggestions are offered based upon the assumption that rasagiline overdose may be modeled after nonselective MAO inhibitor poisoning. Treatment of overdose with nonselective MAO inhibitors is symptomatic and supportive. Respiration should be supported by appropriate measures, including management of the airway, use of supplemental oxygen, and mechanical ventilatory assistance, as required. Body temperature should be monitored closely. Intensive management of hyperpyrexia may be required. Maintenance of fluid and electrolyte balance is essential. For this reason, in cases of overdose with rasagiline, dietary tyramine restriction should be observed for several weeks to reduce the risk of hypertensive tyramine reaction. A poison control center should be called for the most current treatment guidelines. A postmarketing report described a single patient who developed a nonfatal serotonin syndrome after ingesting 100 mg of rasagiline in a suicide attempt. Another patient who was treated in error with 4 mg rasagiline daily and tramadol also developed a serotonin syndrome. One patient who was treated in error with 3 mg rasagiline daily experienced alternating episodes of vascular fluctuations consisting of hypertension and orthostatic hypotension.

Description

Rasagiline tablets contain rasagiline (as the mesylate), a propargylamine-based drug indicated for the treatment of idiopathic Parkinson’s disease. Rasagiline mesylate is designated chemically as: 1H-Inden-1-amine, 2,3-dihydro-N-2-propynyl-,(1R)-, methanesulfonate. The empirical formula of rasagiline mesylate is C 12 H 13 N
• CH 4 SO 3 and its molecular weight is 267.34. Its structural formula is: Rasagiline mesylate is a white to off-white powder, freely soluble in water or ethanol and sparingly soluble in isopropanol. Each rasagiline tablet for oral administration contains 0.5 mg or 1 mg of rasagiline (equivalent to 0.78 mg or 1.56 mg of rasagiline mesylate). Each rasagiline tablet also contains the following inactive ingredients: microcrystalline cellulose, pregelatinized starch, colloidal silicon dioxide, stearic acid, citric acid and talc. str

Mechanism of action

12.1 Mechanism of Action Rasagiline is a selective, irreversible MAO-B inhibitor indicated for the treatment of idiopathic Parkinson’s disease. The results of a clinical trial designed to examine the effects of rasagiline on blood pressure when it is administered with increasing doses of tyramine indicates the functional selectivity can be incomplete when healthy subjects ingest large amounts of tyramine while receiving recommended doses of rasagiline. The selectivity for inhibiting MAO-B diminishes in a dose-related manner. MAO, a flavin-containing enzyme, is classified into two major molecular species, A and B, and is localized in mitochondrial membranes throughout the body in nerve terminals, brain, liver and intestinal mucosa. MAO regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues. MAO-B is the major form in the human brain. In ex vivo animal studies in brain, liver, and intestinal tissues, rasagiline was shown to be a potent, irreversible monoamine oxidase type B (MAO-B) selective inhibitor. Rasagiline at the recommended therapeutic dose was also shown to be a potent and irreversible inhibitor of MAO-B in platelets. The precise mechanisms of action of rasagiline are unknown. One mechanism is believed to be related to its MAO-B inhibitory activity, which causes an increase in extracellular levels of dopamine in the striatum. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagiline’s beneficial effects seen in models of dopaminergic motor dysfunction.

How supplied

Rasagiline tablets 0.5 mg: White to off-white, round, flat, beveled tablets, debossed with “31” on one side and “I” on the other side. Supplied as bottles of 30 tablets with child-resistant cap (NDC 71921-407-33). Rasagiline tablets 1 mg: White to off-white, round, flat, beveled tablets, debossed with “32” on one side and “I” on the other side. Supplied as bottles of 30 tablets with child-resistant cap (NDC 71921-408-33). Storage: Store at 25°C (77°F) with excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]

Label text from the FDA structured product label by Florida Pharmaceutical Products, LLC (revised Feb 23, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Rasagiline Mesylate in 2 products

Rasagiline mesylate NDC products (2)

NDC	Strength & form	Labeler	Type
71921-407	Rasagiline Mesylate .5 mg/1 Tablet	Florida Pharmaceutical Products, LLC	ANDA
71921-408	Rasagiline Mesylate 1 mg/1 Tablet	Florida Pharmaceutical Products, LLC	ANDA

Frequently asked questions

What is Rasagiline mesylate used for?

What are the side effects of Rasagiline mesylate?

Who makes Rasagiline mesylate?

Rasagiline mesylate is listed by 1 labeler in the FDA NDC directory, including Florida Pharmaceutical Products, LLC.