Rasagiline Mesylate - Drug Information | Physicians Office Resource

Overview

Rasagiline mesylate, a propargylamine, is a selective and irreversible inhibitor of monoamine oxidase-B (MAO-B).

Rasagiline mesylate, a propargylamine, is an irreversible monoamine oxidase-B (MAO-B) inhibitor. MAO is a mitochondrial enzyme that regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues. There appear to be at least 2 isoforms of MAO, MAO-A and MAO-B, which differ in localization and substrate specificity.

MAO-A, predominantly found in the GI tract and liver, regulates the metabolic degradation of circulating catecholamines and dietary amines (e.g., tyramine). MAO-B, predominantly found in the brain, regulates the metabolic degradation of dopamine and phenylethylamine. Inhibition of MAO-A in the periphery results in systemic absorption of dietary amines (e.g., tyramine), which, in substantial amounts, can cause release of norepinephrine and subsequent substantial increases in blood pressure. (See Hypertension under Cautions: Warnings/Precautions.) Inhibition of MAO-B results in increased extracellular concentrations of dopamine and, therefore, enhanced dopaminergic activity in the striatum.

While the precise mechanisms of activity of rasagiline have not been fully characterized, data from ex vivo animal studies indicate that the drug potently and irreversibly inhibits MAO-B in brain, liver, and intestinal tissues; the selectivity of rasagiline in inhibiting MAO-B (and not MAO-A) is dose related and diminishes as dosage of the drug is increased above the recommended daily dosage.

Rasagiline is rapidly absorbed; following oral administration, peak plasma concentrations are achieved in approximately 1 hour. The absolute bioavailability of rasagiline is about 36%. Following administration with a high-fat meal, peak plasma rasagiline concentrations and area under the plasma concentration-time curve (AUC) decreased by approximately 60 and 20%, respectively; because AUC is not substantially affected, rasagiline may be administered with or without food.

Rasagiline readily crosses the blood-brain barrier. The mean steady-state or terminal half-life of rasagiline is 3 or 1.34 hours, respectively; however, there is no correlation between rasagiline's pharmacokinetic profile and its pharmacologic effects because the drug irreversibly inhibits MAO-B, and restoration of normal enzyme activity depends on the rate of de novo enzyme synthesis. Rasagiline is approximately 88-94% bound to plasma proteins, with 61-63% bound to albumin.

Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. The drug is metabolized via dealkylation and/or hydroxylation by the cytochrome P-450 (CYP) microsomal enzyme system, principally by isoenzyme 1A2. Approximately 62 and 7% of an oral dose of rasagiline is excreted in urine and feces, respectively, as metabolites over 7 days; less than 1% of the drug is excreted as unchanged drug in urine.

USES: Rasagiline is used alone or with other medications (such as levodopa/carbidopa) to treat symptoms of Parkinson's disease. It can help improve symptoms such as shakiness, stiffness, and difficulty moving. It can also help reduce the amount of "off" time (periods of slow movement or stiffness).

Rasagiline belongs to a class of drugs known as MAO inhibitors. It works by increasing the levels of certain natural substances in the brain (such as dopamine, norepinephrine, serotonin). Parkinson's disease is thought to be caused by too little dopamine in the brain.

Generic name: rasagiline mesylate
Pronunciation: (ra-SA-ji-leen)

Reference product & biosimilars

No reference, biosimilar or interchangeable associated with this drug.

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Indications

The following indications are listed for Rasagiline Mesylate:

Idiopathic Parkinsonism

Also known as: Paralysis Agitans, Primary Parkinson's Disease.

Dosing

The recommended adult dosage of rasagiline as monotherapy or as adjunctive therapy with other antiparkinsonian agents (other than levodopa) in the management of parkinsonian syndrome is 1 mg once daily.

The recommended initial adult dosage of rasagiline as adjunctive therapy with levodopa for the management of parkinsonian syndrome is 0.5 mg once daily. If an adequate response is not achieved, dosage may be increased to 1 mg once daily as tolerated.

The recommended dosages of rasagiline should not be exceeded because of the risk of serious hypertensive reactions.

During adjunctive therapy with levodopa, reduction in levodopa dosage may be considered if adverse dopaminergic effects (e.g., dyskinesia, hallucinations) occur. In clinical studies, approximately 9-17% of patients receiving 0.5 or 1 mg of rasagiline daily required a reduction in levodopa dosage; the average reduction in the daily levodopa dosage was about 9-13%. (See Uses: Parkinsonian Syndrome.)

Concomitant use of rasagiline with ciprofloxacin or other cytochrome P-450 (CYP) isoenzyme 1A2 inhibitors may increase plasma rasagiline concentrations by up to twofold. When used concomitantly with ciprofloxacin or other CYP1A2 inhibitors, rasagiline dosage should not exceed 0.5 mg once daily.

Drug interactions

Rasagiline is extensively metabolized, mainly via hepatic cytochrome P-450 (CYP) 1A2 isoenzyme. The drug does not inhibit CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4, or 4A in vitro.

Contraindications

Concomitant use with cyclobenzaprine, dextromethorphan, meperidine, methadone, propoxyphene (no longer commercially available in the US), tramadol, St. John's wort (Hypericum perforatum), or other monoamine oxidase (MAO) inhibitors (selective or nonselective). (See Drug Interactions.)

Adverse reactions

When rasagiline is used as initial monotherapy, the most common adverse effects (i.e., occurring at least 3% more frequently in patients receiving rasagiline than in those receiving placebo) include flu syndrome, arthralgia, depression, and dyspepsia. Other adverse effects reported in 2% or more of patients receiving rasagiline as initial monotherapy and occurring more frequently with rasagiline than with placebo include fall, headache, conjunctivitis, fever, gastroenteritis, rhinitis, arthritis, ecchymosis, malaise, neck pain, paresthesia, and vertigo.

When rasagiline is used as adjunctive therapy with levodopa, the most common adverse effects (i.e., occurring at least 3% more frequently in patients receiving rasagiline than in those receiving placebo) include dyskinesia, accidental injury, weight loss, orthostatic hypotension, vomiting, anorexia, arthralgia, abdominal pain, nausea, constipation, dry mouth, rash, abnormal dreams, and fall. Other adverse effects reported in 2% or more of patients receiving rasagiline as initial monotherapy and occurring more frequently with rasagiline than with placebo include ecchymosis, somnolence, paresthesia, headache, diarrhea, dyspepsia, hallucinations, ataxia, dyspnea, infection, neck pain, sweating, tenosynovitis, dystonia, gingivitis, hemorrhage, hernia, and myasthenia.

When rasagiline is used as adjunctive therapy with a dopamine agonist, the most common adverse effects include peripheral edema, fall, arthralgia, cough, and insomnia.

Precautions

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ICD codes

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Formulary status

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Rasagiline Mesylate (rasagiline mesylate)