Rasagiline

Uses

Rasagiline is used for the treatment of the signs and symptoms of idiopathic Parkinson's disease as initial monotherapy, and as adjunct therapy to dopamine agonists or to levodopa.
Pediatric use: The safety and effectiveness in pediatric patients have not been established.

Rasagiline is also used to associated treatment for these conditions: Parkinson's Disease (PD)

How Rasagiline works

The precise mechanisms of action of rasagiline is 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.

Dosage

Rasagiline dosage

Monotherapy: Rasagiline 1 mg once daily
As adjunct without Levodopa: Rasagiline 1 mg once daily
As adjunct to Levodopa: Rasagiline 0.5 mg once daily

Side Effects

Common side effects of Rasagiline include: dizziness, spinning sensation, joint pain, headache, heartburn, nausea, muscle pain etc.

Toxicity

Signs and symptoms of overdosage may include, alone or in combination, any of the following: 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.

Precaution

Exacerbation of hypertension may occur during treatment with Rasagiline. Medication adjustment may be necessary if elevation of blood pressure is sustained. Dose should not exceed 0.5 mg once daily for patients with mild hepatic impairment or taking concomitant Ciprofloxacin or other CYP1A2 inhibitors.

Interaction

Concomitant use of Rasagiline with meperidine, dextromethorphan, antidepressants is not recommended.

Food Interaction

• Avoid St. John's Wort. Co-administration of rasagiline with this herb is contraindicated.
• Avoid tyramine-containing foods and supplements. Avoid food containing high amounts of tyramine (>150mg) as these may increase the risk of hypertensive reaction. Tyramine-containing foods include cheese, red wine, fava beans, pickled food, cured food, and alcoholic beverages.
• Take with or without food.

[Moderate] GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase (MAO) inhibitors.

The mechanism involves inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact.

Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules.

Although rasagiline is a selective inhibitor of MAO-B at the recommended dosages of 0.5 or 1 mg

There were no cases of hypertensive crisis in the clinical development program associated with rasagiline treatment at 1 mg

However, rare cases of hypertensive crisis have been reported during the postmarketing period in patients who ingested unknown amounts of tyramine-rich foods while taking recommended dosages of rasagiline or selegiline, another MAO-B inhibitor.

Rasagiline peak plasma concentration (Cmax) and systemic exposure (AUC ) are decreased by approximately 60% and 20%, respectively, during coadministration with a high-fat meal.

The time to peak concentration (Tmax) is not affected by food.

MANAGEMENT: Dietary restriction is not ordinarily required during rasagiline treatment with respect to most foods and beverages that may contain tyramine such as air-dried and fermented meats or fish, aged cheeses, most soybean products, yeast extracts, red wine, beer, and sauerkraut.

However, certain foods like some of the aged cheeses (e.g., Boursault, Liederkrantz, Mycella, Stilton) may contain very high amounts of tyramine and could potentially cause a hypertensive reaction in patients taking rasagiline even at recommended dosages due to increased sensitivity to tyramine.

Patients should be advised to avoid ingesting very high levels of tyramine (e.g., greater than 150 mg), and to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, confusion, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms.

Rasagiline should not be used at dosages exceeding 1 mg

Rasagiline can be administered with or without food.

Rasagiline Alcohol interaction

[Moderate] GENERALLY AVOID:

Alcohol may potentiate some of the pharmacologic effects of central nervous system (CNS)-active agents.

Use in combination may result in additive CNS depression and/or impairment of judgment, thinking, and psychomotor skills.

Patients receiving CNS-active agents should be advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled against driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Rasagiline Hypertension interaction

[Moderate] Exacerbation of hypertension may occur during treatment with rasagiline.

Dosage adjustment may be necessary if the elevation is sustained.

Patients should be monitored for new onset hypertension or hypertension that is not well controlled after starting treatment.

Rasagiline Drug Interaction

Moderate: metoprolol, rotigotine, carbidopa / levodopa, carbidopa / levodopa, carbidopa / levodopa, sildenafilUnknown: aspirin, aspirin, ubiquinone, rosuvastatin, apixaban, omega-3 polyunsaturated fatty acids, atorvastatin, polyethylene glycol 3350, mirabegron, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, rivaroxaban

Rasagiline Disease Interaction

Major: hypotension, psychosis, hepatic impairmentModerate: hypertension, renal impairment

Volume of Distribution

• 87 L

Elimination Route

Rasagiline is rapidly absorbed following oral administration. The absolute bioavailability of rasagiline is about 36%.

Half Life

Rasagiline has a mean steady-state half life of 3 hours but there is no correlation of pharmacokinetics with its pharmacological effect because of its irreversible inhibition of MAO-B.

Elimination Route

Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. Glucuronide conjugation of rasagiline and its metabolites, with subsequent urinary excretion, is the major elimination pathway. After oral administration of 14C-labeled rasagiline, elimination occurred primarily via urine and secondarily via feces (62% of total dose in urine and 7% of total dose in feces over 7 days), with a total calculated recovery of 84% of the dose over a period of 38 days. Less than 1% of rasagiline was excreted as unchanged drug in urine.

Pregnancy & Breastfeeding use

Pregnancy Category C. Rasagiline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether this drug is excreted in human milk. So, caution should be exercised when administered to a nursing woman.

Contraindication

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.

Storage Condition

Store below 30° c, protected from light and moisture. Keep all the medicines out of reach of children.

Innovators Monograph

You find simplified version here Rasagiline