Usage
- Rasagiline is prescribed for the treatment of Parkinson’s disease (PD), either as monotherapy or as adjunct therapy to levodopa.
- Pharmacological classification: Monoamine oxidase-B (MAO-B) inhibitor.
- Mechanism of action: Rasagiline selectively and irreversibly inhibits MAO-B, an enzyme responsible for breaking down dopamine in the brain. This action increases dopamine levels, thereby improving motor control and reducing PD symptoms.
Alternate Names
- Rasagiline mesylate (salt form)
- Brand names: Azilect®, APO-Rasagiline®, TEVA-Rasagiline®, Rasagiline ratiopharm®, JAMP Rasagiline®
How It Works
- Pharmacodynamics: Rasagiline primarily exerts its therapeutic effect by increasing dopaminergic activity in the brain. It may also have neuroprotective effects.
- Pharmacokinetics:
- Absorption: Rasagiline is rapidly absorbed after oral administration, reaching peak plasma concentrations within approximately 0.5 to 1.5 hours.
- Metabolism: Rasagiline is extensively metabolized in the liver, primarily by CYP1A2. The major metabolites are 1-aminoindan and 3-hydroxy-N-propargyl-1-aminoindan.
- Elimination: Metabolites are primarily excreted in the urine. The elimination half-life of rasagiline is approximately 0.6 to 2 hours.
- Mode of action: Rasagiline irreversibly binds to and inhibits MAO-B, preventing the breakdown of dopamine. This leads to increased dopamine levels in the synaptic cleft, enhancing dopaminergic neurotransmission.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Rasagiline is a highly selective and irreversible inhibitor of MAO-B. At higher doses, it loses selectivity and can also inhibit MAO-A.
- Elimination pathways: Primarily hepatic metabolism followed by renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Monotherapy: 1 mg orally once daily.
- Adjunct therapy (with levodopa): Initial dose: 0.5 mg orally once daily. May be increased to 1 mg once daily if needed and tolerated. Consider reducing levodopa dose upon rasagiline initiation.
- Adjunct therapy (without levodopa): 1 mg orally once daily.
Children:
- Safety and efficacy not established in patients younger than 18 years.
Special Cases:
- Elderly Patients: No specific dosage adjustments recommended. However, close monitoring for adverse effects is advisable.
- Patients with Renal Impairment: No dosage adjustment required for mild-to-moderate impairment. Not studied in severe renal impairment.
- Patients with Hepatic Dysfunction:
- Mild impairment (Child-Pugh A): Maximum dose of 0.5 mg daily.
- Moderate-to-severe impairment (Child-Pugh B/C): Contraindicated.
- Patients with Comorbid Conditions: Dose adjustment may be required based on specific conditions.
Clinical Use Cases
Rasagiline is specifically indicated for Parkinson’s disease. The dosages for clinical use cases within PD management are covered under the standard dosage guidelines. It is not indicated for Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, or Emergency Situations (e.g., status epilepticus, cardiac arrest).
Dosage Adjustments
- Coadministration with CYP1A2 inhibitors (e.g., ciprofloxacin): Maximum dose of 0.5 mg daily.
Side Effects
Common Side Effects
- Headache
- Joint pain
- Indigestion
- Nausea
- Flu-like symptoms
- Dizziness
- Drowsiness
- Insomnia
Rare but Serious Side Effects
- Hallucinations
- Psychotic-like behaviors
- Impulse control disorders (e.g., gambling, hypersexuality)
- Orthostatic hypotension
- Allergic reactions
- Hypertension, including hypertensive crisis (especially with tyramine-rich foods)
Long-Term Effects
The potential long-term effects of rasagiline are still under investigation. Some studies suggest a possible increased risk of melanoma with prolonged use.
Adverse Drug Reactions (ADR)
- Serotonin syndrome (with concomitant use of serotonergic drugs)
Contraindications
- Hypersensitivity to rasagiline or any of its components
- Concomitant use of:
- Meperidine
- Tramadol
- Methadone
- Propoxyphene
- MAO inhibitors (including other MAO-B inhibitors)
- St. John’s wort
- Cyclobenzaprine
- Dextromethorphan
- Moderate-to-severe hepatic impairment (Child-Pugh B/C)
Drug Interactions
- CYP1A2 inhibitors: Increased rasagiline levels (dose adjustment required).
- Serotonergic drugs (e.g., SSRIs, SNRIs, tricyclic antidepressants): Risk of serotonin syndrome.
- Tyramine-containing foods: Risk of hypertensive crisis.
- Sympathomimetics: Enhanced effects.
- Dopamine agonists: Possible additive effects.
- Fluoxetine, fluvoxamine: Increased risk of serotonin syndrome.
- Smoking: Decreased rasagiline levels.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (US FDA), B3 (Australia TGA)
- Fetal risks: Potential for embryolethality, especially with concomitant levodopa/carbidopa use. Insufficient data in humans.
- Breastfeeding: Rasagiline may inhibit prolactin secretion and potentially lactation. It is unknown if rasagiline is excreted in breast milk. Use with caution. Consider potential risks to the infant.
Drug Profile Summary
- Mechanism of Action: Selective, irreversible MAO-B inhibitor, increasing dopamine levels in the brain.
- Side Effects: Headache, dizziness, joint pain, nausea, insomnia, impulse control disorders, hallucinations.
- Contraindications: Concomitant use of MAOIs, pethidine, tramadol, dextromethorphan, St. John’s wort, cyclobenzaprine; moderate-to-severe hepatic impairment.
- Drug Interactions: CYP1A2 inhibitors, serotonergic drugs, tyramine-containing foods, fluoxetine, fluvoxamine, smoking.
- Pregnancy & Breastfeeding: Category C (US FDA), B3 (Australia TGA); Use with caution during pregnancy and breastfeeding.
- Dosage: 1 mg/day (monotherapy or without levodopa); 0.5 mg/day initially, may increase to 1 mg/day (with levodopa).
- Monitoring Parameters: Blood pressure, motor symptoms, psychiatric status.
Popular Combinations
- Levodopa/carbidopa: Rasagiline is often used as an adjunct to levodopa to improve motor control and reduce motor fluctuations.
Precautions
- Monitor blood pressure, especially during dose initiation and with tyramine-containing foods.
- Assess for impulse control disorders, hallucinations, and suicidal ideation.
- Monitor for signs of serotonin syndrome with concomitant use of serotonergic drugs.
- Caution in patients with hepatic impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Rasagiline?
A: 1 mg once daily for monotherapy or as adjunct therapy without levodopa. 0.5 mg once daily initially, which can be increased to 1 mg/day, when used as adjunctive therapy with levodopa.
Q2: What are the common side effects of Rasagiline?
A: Common side effects include headache, joint pain, indigestion, nausea, flu-like symptoms, dizziness, drowsiness, and insomnia.
Q3: How does Rasagiline interact with other medications?
A: Rasagiline interacts with several medications, including CYP1A2 inhibitors (e.g., ciprofloxacin), serotonergic drugs (e.g., SSRIs, SNRIs), and tyramine-containing foods. Consult the ‘Drug Interactions’ section for a comprehensive list.
Q4: Can Rasagiline be used during pregnancy and breastfeeding?
A: Rasagiline should be used with caution during pregnancy and breastfeeding. Consult the ‘Pregnancy and Breastfeeding’ section for detailed information.
Q5: What is the mechanism of action of Rasagiline?
A: Rasagiline is a selective, irreversible inhibitor of MAO-B, preventing dopamine breakdown and increasing its levels in the brain.
Q6: What are the contraindications for Rasagiline use?
A: Contraindications include hypersensitivity to rasagiline, concomitant use of MAO inhibitors, pethidine, tramadol, dextromethorphan, St. John’s wort, cyclobenzaprine, and moderate-to-severe hepatic impairment.
Q7: What are the signs and symptoms of serotonin syndrome?
A: Symptoms of serotonin syndrome can include agitation, confusion, tachycardia, hypertension, muscle rigidity, hyperthermia, and diaphoresis.
Q8: What should patients avoid while taking Rasagiline?
A: Patients should avoid tyramine-rich foods (aged cheese, cured meats, fermented products) to minimize the risk of hypertensive crisis. They should also avoid alcohol and other medications that can cause drowsiness.
Q9: How should Rasagiline be administered?
A: Rasagiline should be administered orally once daily, with or without food.
A: Warning signs include signs of allergic reaction, signs of impulse control disorders, hallucinations, psychotic behavior, severe hypertension, and symptoms of serotonin syndrome.
