Rasagiline
Rasagiline Uses, Dosage, Side Effects, Food Interaction and all others data.
Rasagiline is a potent, irreversible, selective MAO-B inhibitor that effectively crosses the blood brain barrier after oral administration. 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 brain. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate Rasagiline's beneficial effects.
Rasagiline is a propargylamine and an irreversible inhibitor of monoamine oxidase (MAO). MAO, a flavin-containing enzyme, regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues. It 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-A is found predominantly in the GI tract and liver, and regulates the metabolic degradation of circulating catecholamines and dietary amines. MAO-B is the major form in the human brain and is responsible for the regulation of the metabolic degradation of dopamine and phenylethylamine. In ex vivo animal studies in brain, liver and intestinal tissues rasagiline was shown to be a potent,selective, and irreversible monoamine oxidase type B (MAO-B) inhibitor. At the recommended therapeutic doses, Rasagiline was also shown to be a potent and irreversible inhibitor of MAO-B in platelets. The selectivity of rasagiline for inhibiting only MAO-B (and not MAO-A) in humans and the sensitivity to tyramine during rasagiline treatment at any dose has not been sufficiently characterized to avoid restriction of dietary tyramine and amines contained in medications.
Trade Name | Rasagiline |
Availability | Prescription only |
Generic | Rasagiline |
Rasagiline Other Names | Rasagilina, Rasagiline |
Related Drugs | Neupro, Azilect, Duopa, Apokyn, Xadago, Ongentys, Gocovri, Rytary, Sinemet, Sinemet CR |
Weight | 0.5mg, 1mg |
Type | Oral tablet |
Formula | C12H13N |
Weight | Average: 171.2383 Monoisotopic: 171.104799421 |
Protein binding | Plasma protein binding ranges from 88-94% with mean extent of binding of 61-63% to human albumin over the concentration range of 1-100 ng/ml. |
Groups | Approved |
Therapeutic Class | Antiparkinson drugs |
Manufacturer | Glenmark Pharmaceuticals Europe Ltd |
Available Country | United Kingdom, United States |
Last Updated: | September 19, 2023 at 7:00 am |
![Rasagiline Rasagiline](https://www.medicinesfaq.com/media/png/rasagiline.png)
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. The time to peak concentration (Tmax) is not affected by food. 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 peak plasma concentration (Cmax) and systemic exposure (AUC ) are decreased by approximately 60% and 20%, respectively, during coadministration with a high-fat meal.
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.
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.
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