Rasagiline

Pronunciation: ra-SA-ji-leen
Class: Antiparkinson agent

Trade Names

Azilect
- Tablets, oral 0.5 mg
- Tablets, oral 1 mg

Pharmacology

Irreversible monoamine oxidase type B (MAO-B) inhibitor suspected to increase extracellular levels of dopamine.

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Pharmacokinetics

Absorption

Rapidly absorbed, reaching C max in approximately 1 h. Bioavailability is about 36%. Food does not affect the T max , but C max and AUC are decreased approximately 60% and 20%, respectively.

Distribution

Vd at steady state is 87 L, indicating tissue binding exceeds plasma protein binding. Plasma protein binding ranges from 88% to 94%.

Metabolism

Almost complete metabolism in the liver by N-dealkylation and/or hydroxylation prior to excretion.

Elimination

Steady-state half-life is 3 h. Primarily eliminated in the urine (62%) and secondarily in the feces (7%) over 7 days.

Special Populations

Hepatic Function Impairment

In patients with mild hepatic impairment, AUC and C max are increased 2- and 1.4-fold, respectively. In patients with moderate hepatic impairment, the AUC and C max are increased 7- and 2-fold, respectively.

Indications and Usage

Treatment of signs and symptoms of idiopathic Parkinson disease as initial monotherapy or as an adjunct therapy to levodopa.

Contraindications

Coadministration with meperidine, methadone, mirtazapine, propoxyphene, tramadol, dextromethorphan, St. John's wort, cyclobenzaprine, methylphenidate, dexmethylphenidate, or other MAOIs.

Dosage and Administration

Adults

PO Monotherapy: 1 mg/day (max). Adjunctive therapy: 0.5 mg/day initially; increase dosage to 1 mg/day (max) if clinical response is not sufficient.

Hepatic Function Impairment
Adults

PO 0.5 mg/day (max) in patients with mild hepatic impairment. Do not use rasagiline in patients with moderate or severe hepatic impairment.

CYP1A2 inhibitors (eg, ciprofloxacin)
Adults

PO 0.5 mg/day (max).

General Advice

  • Administer with or without food. Dietary tyramine restriction is not ordinarily required. Certain foods (eg, aged cheeses) may contain very high amounts of tyramine and could potentially cause a hypertensive “cheese” reaction in patients taking rasagiline even at the recommended dose.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Amine- and tyramine-containing foods

May be associated with hypertensive crisis requiring immediate treatment and possible hospitalization.

Analgesics (eg, meperidine, methadone, propoxyphene, tramadol), cocaine, cyclobenzaprine, mirtazapine, St. John's wort

Coadministration with rasagiline is contraindicated. Coadministration with meperidine may increase the risk of severe reactions, including apnea, coma, seizures, and death.

Antidepressants (eg, bupropion, SSRIs [eg, fluoxetine, fluvoxamine, paroxetine, sertraline], SNRIs [eg, venlafaxine], trazodone, tricyclic antidepressants [eg, amitriptyline])

Serious, sometimes fatal, reactions with signs and symptoms including autonomic instability, coma, delirium, hyperthermia, myoclonus, and rigidity may occur. At least 14 days should elapse between discontinuation of rasagiline and initiation of treatment with an antidepressant. At least 5 weeks should elapse between discontinuation of fluoxetine and initiation of rasagiline.

Buspirone

The risk of adverse effects, including severe hypertension, may be increased. Coadministration is not recommended.

CYP1A2 inhibitors (eg, ciprofloxacin, mexiletine, tacrine)

Rasagiline plasma concentrations may be elevated 2-fold, increasing the pharmacologic and adverse effects. The daily dose of rasagiline should not exceed 0.5 mg.

Dexmethylphenidate, methylphenidate

Pharmacologic effects of dexmethylphenidate and methylphenidate may be increased. Headache, GI symptoms, and hypertension may occur. Coadministration of dexmethylphenidate and rasagiline is contraindicated.

Dextromethorphan

Contraindicated; episodes of psychosis and bizarre behavior have been reported. Risk of hypotension, coma, and death may be increased.

Levodopa

Dopaminergic adverse reactions and exacerbation of preexisting dyskinesia may be potentiated. The levodopa dose may need to be reduced.

Norepinephrine reuptake inhibitors (eg, atomoxetine, tapentadol)

The effects may be additive, increasing the risk of toxicity. Coadministration within 14 days is contraindicated.

Other MAOIs

Contraindicated; there may be an increased risk of nonselective MAO inhibition, leading to hypertensive crisis.

Sibutramine

The risk of serotonin syndrome (eg, agitation, altered consciousness, ataxia, myoclonus overactive reflexes, shivering) may be increased. Avoid coadministration.

Sympathomimetic amines (eg, dopamine, pseudoephedrine)

Risk of severe headache, hypertension, and hypertensive crisis may be increased. If coadministration cannot be avoided, use with caution.

Tetrabenazine

Coadministration may result in severe unexpected toxicity (eg, confusion, restlessness, behavioral changes). Coadministration is contraindicated.

Adverse Reactions

Cardiovascular

Angina pectoris, bundle branch block, syncope (at least 1%).

CNS

Headache (14%); depression (5%); malaise, paresthesia, vertigo (2%); abnormal gait, anxiety, asthenia, decreased libido, dizziness, hallucinations, hyperkinesia, hypertonia, neuropathy, tremor (at least 1%); impulse control symptoms, increased libido including hypersexuality, pathological gambling (postmarketing).

Dermatologic

Alopecia, skin carcinoma, vesiculobullous rash (at least 1%).

EENT

Conjunctivitis, rhinitis (3%).

GI

Dyspepsia (7%); gastroenteritis (3%); anorexia, diarrhea, GI hemorrhage, vomiting (at least 1%).

Genitourinary

Albuminuria, hematuria, impotence, urinary incontinence (at least 1%).

Hematologic-Lymphatic

Ecchymosis (2%); leukopenia (at least 1%).

Hepatic

Abnormal LFTs (at least 1%).

Musculoskeletal

Arthralgia (7%); arthritis, neck pain (2%).

Respiratory

Asthma, increased cough (at least 1%).

Miscellaneous

Falling, flu syndrome (5%); fever (3%); allergic reaction, chest pain (at least 1%).

Precautions

Monitor

Periodic skin examinations for melanomas.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy have not been established.

CNS effects

Hallucinations and psychotic-like behavior may occur.

Dyskinesia

May cause dyskinesia or potentiate dopaminergic adverse effects and exacerbate preexisting dyskinesia when used as an adjunct to levodopa.

High blood pressure

Incidence of significantly high blood pressure is increased when used in conjunction with levodopa.

Hypertensive crisis

Rare cases have been reported in patients after ingesting tyramine-rich foods. Dietary tyramine restriction is not ordinarily required during treatment with recommended doses of rasagiline.

Melanoma

Risk of melanoma may be increased, although it is unclear if the increased risk is because of rasagiline therapy or Parkinson disease.

Postural hypotension

Occurs most frequently in the first 2 mo of treatment.

Withdrawal

A symptom complex resembling NMS (eg, elevated temperature, muscular rigidity, altered consciousness, autonomic instability) has been reported in association with rapid dose reduction, withdrawal of, or changes in drugs that increase central dopaminergic tone.

Overdosage

Symptoms

Agitation, coma, convulsions, cool and clammy skin, death, diaphoresis, dizziness, drowsiness, faintness, hallucinations, hyperactivity, hyperpyrexia, hypertension, hypotension, irritability, opisthotonos, orthostatic hypotension, precordial pain, rapid and irregular pulse, respiratory depression and failure, severe headache, trismus, vascular collapse.

Patient Information

  • Advise patients to avoid certain foods (eg, aged cheese) containing a very large amount of tyramine.
  • Instruct patients about the signs and symptoms of marked BP elevation that could represent a hypertensive emergency.
  • Instruct patients to immediately contact their health care provider if severe headache or other atypical or unusual symptoms that could be caused by hypertensive crisis occur.
  • Advise patients to take the medication as prescribed.
  • Advise patients that if a dose is missed to take the next dose at the usual time on the following day.
  • Advise patients that they may develop orthostatic hypotension and that it may occur more frequently during the initiation of therapy or with an increase in dose. Caution patients about standing rapidly after sitting or lying down.
  • Alert patients to the possibility of BP increases and inform them that exacerbation of hypertension may occur.
  • Inform patients that hallucinations, other psychotic-like behavior, and intense urges (eg, gambling, sexual urges) may occur.

Copyright © 2009 Wolters Kluwer Health.

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