Rasagiline Mesylate (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- AZILECT
- RASAGILINE MESYLATE
Indications and Usage
Rasagiline tablets are indicated for the treatment of Parkinson’s disease (PD).
Contraindications
Rasagiline is 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 and initiation of treatment with these medications. Rasagiline is contraindicated for use with St. John’s wort and with cyclobenzaprine. Rasagiline is contraindicated for use with dextromethorphan because of risk of episode of psychosis or bizarre behavior.
Adverse Reactions
The following adverse reactions are described in more detail in the Warnings and Precautionssection 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)]
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 vivoanimal 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.
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 ven