Rasagil

Approved Indications:

• Idiopathic Parkinson’s Disease (PD):
• As monotherapy in early-stage Parkinson’s disease.
• As adjunct therapy to levodopa in patients experiencing “off” episodes (i.e., end-of-dose motor fluctuations).

Clinically Accepted Off-Label Uses:

• Parkinson’s Disease Dementia (investigational):
• Studied for potential cognitive benefits, though not currently approved for this indication.
• Neuroprotection (investigational):
• Ongoing research for disease-modifying effects in PD due to its anti-apoptotic properties.

Adults:

• Monotherapy:
  1 mg orally once daily.
• Adjunct to Levodopa:
  0.5 mg orally once daily, may be increased to 1 mg once daily based on response and tolerability.

Administration Notes:

• May be taken with or without food.
• Swallow tablets whole; do not crush or split.

Geriatric Use:

• No dosage adjustment necessary. However, increased monitoring for adverse effects is advised in elderly patients.

Hepatic Impairment:

• Mild impairment: Use with caution.
• Moderate to severe impairment: Contraindicated.

Renal Impairment:

• No dose adjustment required.

Pediatrics:

• Safety and efficacy in individuals under 18 years of age have not been established; not recommended.

Rasagiline is a selective, irreversible inhibitor of monoamine oxidase-B (MAO-B), an enzyme that breaks down dopamine in the brain. By inhibiting MAO-B, rasagiline increases the synaptic availability of dopamine, enhancing dopaminergic activity in the striatum, which improves motor function and reduces symptoms of Parkinson's disease. Additionally, rasagiline may exert neuroprotective effects through its propargylamine structure, which has been shown to inhibit apoptosis and oxidative stress in neuronal cells.

• Absorption:
  Rapid oral absorption; peak plasma levels occur within 0.5–1 hour.
• Bioavailability:
  Approximately 36%.
• Distribution:
  Widely distributed; plasma protein binding ~88–94%.
• Metabolism:
  Extensively metabolized by CYP1A2 to inactive metabolites.
• Active Metabolites:
  No active metabolites; primary metabolite is aminoindan.
• Half-life:
  3 hours (but pharmacodynamic effect lasts longer due to irreversible MAO-B inhibition).
• Elimination:
  Primarily via urine (62%) and feces (7%) as metabolites.

• Pregnancy:
  Classified under FDA Pregnancy Category C (prior to PLLR format). No adequate human data available. Animal studies have shown potential fetal risk. Use only if the benefits justify the risk to the fetus.
• Lactation:
  Unknown whether rasagiline is excreted into human breast milk. Due to potential risk, caution is advised if administered during breastfeeding.

• Primary Class: Antiparkinsonian Agent
• Subclass: Selective Monoamine Oxidase-B (MAO-B) Inhibitor
• Generation: Second-generation MAO-B inhibitor

• Known hypersensitivity to rasagiline or any component of the formulation
• Use with meperidine, tramadol, methadone, propoxyphene, or other MAO inhibitors
• Concomitant use of St. John's Wort or cyclobenzaprine
• Moderate to severe hepatic impairment
• Concurrent use with sympathomimetic ophthalmic preparations

• Serotonin Syndrome:
  Risk increases when used with SSRIs, SNRIs, TCAs, or other serotonergic drugs.
• Hypertensive Crisis:
  Avoid tyramine-rich foods in large quantities, although dietary restrictions are generally not necessary at recommended doses.
• Dyskinesia and Hallucinations:
  May exacerbate levodopa-induced dyskinesias or cause hallucinations when used in combination.
• Postural Hypotension:
  May occur, especially in elderly or those on antihypertensive agents.
• Melanoma Risk:
  Parkinson’s patients may have increased melanoma risk; skin examinations are recommended.
• Withdrawal:
  Gradual tapering may not be necessary due to irreversible inhibition, but clinical monitoring is advised if stopped.

Common (≥1%):

• Headache
• Arthralgia
• Indigestion
• Depression
• Flu-like symptoms
• Conjunctivitis
• Insomnia

In Combination with Levodopa:

• Dyskinesia
• Hallucinations
• Postural hypotension
• Nausea
• Dry mouth
• Constipation

Serious Adverse Events:

• Serotonin syndrome (rare but serious)
• Hypertensive crisis (with tyramine overload)
• Hallucinations or psychosis
• Melanoma (rare; surveillance recommended)

Onset:

• Within days to weeks of initiation. Some effects (e.g., dyskinesia) may be dose- or levodopa-dependent.

• Strong CYP1A2 inhibitors (e.g., ciprofloxacin):
  May increase rasagiline plasma levels—use with caution.
• MAO Inhibitors (non-selective):
  Contraindicated—risk of hypertensive crisis or serotonin syndrome.
• Serotonergic Drugs (SSRIs, SNRIs, TCAs):
  Risk of serotonin syndrome—co-administration should be done with caution.
• Sympathomimetics (including OTC nasal decongestants):
  May increase blood pressure.
• Tyramine-rich foods (e.g., aged cheeses, red wine):
  Normally safe at recommended doses, but large quantities may trigger hypertensive response.
• Dextromethorphan:
  Avoid co-use—risk of psychosis or bizarre behavior.

• 2022–2024 (AAN and MDS Updates):
  Rasagiline continues to be recommended as an effective monotherapy or adjunct in early and advanced PD.
  Emphasis placed on its neuroprotective potential, though not yet formally proven in disease-modifying trials.
• Label Update (FDA):
  Clarified warnings regarding serotonin syndrome and drug-drug interactions.
• Ongoing Investigations:
  Studied in combination with safinamide or other agents for enhancing motor control in PD.

• Storage Temperature:
  Store at 20°C to 25°C (68°F to 77°F).
  Excursions permitted between 15°C and 30°C (59°F–86°F).
• Humidity & Light Protection:
  Store in a dry place, protect from excessive moisture and direct light.
• Handling Precautions:
  Keep in original container until use; keep out of reach of children.
• No Refrigeration Required.