Each tablet contains rasagiline 1 mg.
Pharmacotherapeutic Group: Anti-Parkinson's Agent, MAO Type B. Inhibitor.
Pharmacology: Pharmacodynamics: Mechanism of Actions: Potent, irreversible and selective inhibitor of brain monoamine oxidase (MAO) type B, which plays a major role in the catabolism of dopamine. Inhibition of dopamine depletion in the striatal region of the brain reduces the symptomatic motor deficits of Parkinson's disease. There is also experimental evidence of rasagiline conferring neuroprotective effects (antioxidant, antiapoptotic), which may delay onset of symptoms and progression of neuronal deterioration.
Pharmacokinetics: Duration: ~1 week (irreversible inhibition).
Protein binding: 88% to 94%, primarily to albumin.
Metabolism: Hepatic N-dealkylation and/or hydroxylation via CYP1A2 to multiple inactive metabolites.
Distribution: Vdss: 87 L.
Half-life elimination: ~3 hours (no correlation with biologic effect due to irreversible inhibition).
Time to peak, plasma: ~1 hour.
Excretion: Urine (62%, <1% of total dose as unchanged drug); feces (7%).
Toxicology: Range of Toxicity: MAO-B INIHIBITORS: Rasagiline 2 mg/day caused mild symptoms in healthy adults. Patients on chronic levodopa therapy developed hypertension and orthostatic hypotension with 10 g rasagiline.
Treatment: MAO-B INHIBITORS: Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: All patients with symptoms of MAOI toxicity should be evaluated by a health care professional. Symptoms may persist for several weeks due to the irreversibility of MAO inhibition caused by these medications. Discontinuation of the offending agents and patient education involving drug interactions should be provided to all symptomatic patients.
MANAGEMENT OF SEVERE TOXICITY: Careful attention to the ABCs (airway, breathing and circulation) should guide symptomatic and supportive treatment, which is the mainstay of MAOI toxicity management.
There is no antidote for MAOI toxicity.
Treatment of Parkinson disease.
Oral: Adults: Parkinson disease: Monotherapy or adjunctive therapy (not including levodopa): 1 mg once daily (maximum: 1 mg once daily).
Adjunctive therapy with levodopa: Initial: 0.5 mg once daily; may increase to 1 mg once dailY based on response and tolerability (maximum: 1 mg once daily).
Dose reduction with concomitant ciprofloxacin or other CYP1A2 inhibitors: Maximum dose: 0.5 mg once daily.
Dosage adjustment in renal impairment: Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Dosage adjustment in hepatic impairment: Mild impairment (Child-Pugh score 5 to 6): Maximum dose: 0.5 mg once daily.
Moderate to severe impairment (Child-Pugh score 7 to 15): Use is not recommended.
Dietary Considerations: Avoid products containing high amount of tyramine (> 150 mg), such as aged cheeses (eg, Stilton cheese).
Administration: Administer without regard to meals.
Concomitant use of an MAO inhibitor (including selective MAO-B inhibitors), meperidine, methadone, propoxyphene, or tramadol within 14 days of rasagiline; concomitant use with cyclobenzaprine, dextromethorphan, or St John's wort.
Cardiovascular: New onset or exacerbation of hypertension (HTN) may occur; if HTN sustained, dose adjustment may be necessary; monitoring recommended.
Hypotension and orthostatic hypotension have been reported; occurs most often in first 2 months of therapy; risk may increase when used as adjunct therapy.
Dermatologic: Increased risk of melanoma in patients with Parkinson disease; monitoring recommended.
Hepatic: Reduce dose in patients with mild hepatic impairment.
Avoid use in patients with moderate or severe hepatic impairment.
Neurologic: Serotonin syndrome has been reported; concomitant use with certain antidepressants not recommended.
Somnolence and falling asleep during activities of daily living may occur without warning, sometimes more than 1 year after treatment initiation; increased risk with preexisting sleep disorders, concomitant sedatives or drugs that increase rasagiline exposure; monitoring recommended; discontinue with significant episodes.
New or worsening dyskinesia may occur when administered with levodopa; levodopa dose adjustment may lesson reaction.
Hyperpyrexia and confusion resembling neuroleptic malignant syndrome has been reported with abrupt withdrawal, rapid dose reduction, or changes in dopaminergic drugs.
Psychiatric: Hallucinations , new or worsening mental stat us changes, and behavioral changes, including psychotic-like behavior, have been reported when starting, with dose increases, and during therapy; dose reduction or therapy withdrawal may be necessary.
Use in major psychotic disorder not recommended due to risk of psychosis exacerbation.
Impaired impulse control or compulsive behaviors has been reported, including urges to gamble or spend money, increased sexual urges, or binge eating; consider dose reduction or therapy withdrawal.
Concomitant use: Foods with high tyramine content (more than 150 mg) should be avoided; increased risk for large blood pressure elevations, including hypertensive emergency, urgency, or crisis.
Antidepressants (eg, SSRIs, selective norepinephrine reuptake inhibitors, or tricyclic, tetracyclic, or triazolopyridine antidepressants) not recommended; allow at least 14 days between rasagiline discontinuation and antidepressant initiation; wait at least 5 weeks after discontinuing antidepressants with long half-life (eg, fluoxetine, particularly high doses or chronic use) before rasagiline initiation.
Ciprofloxacin and other CYP1A2 inhibitors increases rasagiline exposure; dose adjustment recommended.
Pregnancy Risk Factor: C.
Pregnancy Considerations: Adverse effects have been observed in animal reproduction studies.
Breast-feeding Considerations: It is not known if rasagiline is excreted in breast milk. The manufacturer recommends caution be exercised when administering rasagiline to nursing women.
Orthostatic hypotension (7% to 44% ), Peripheral edema (7% ).
Rash (3% to 6% ).
Weight decreasing (2% to 9% ).
Constipation (4% to 9% ), Indigestion (4% to 7% ), Nausea (6% to 12% ), Vomiting (4% to 7% ), Xerostomia (2% to 6% )
Arthralgia (5% to 11% ).
Ataxia (3% to 6% ), Dizziness (7% ), Dyskinesia (18% ), Headache (6% to 14% ).
Depression (5% ).
Falling injury (5% to 12% ), Influenza-like illness (5% )
Hypertension (4% ).
N04BD02 - rasagiline ; Belongs to the class of dopaminergic agents, monoamine oxidase B inhibitors. Used in the management of Parkinson's disease.