Section 03 · Monograph

Rasagiline

Reviewed Nov 2026FDA label

AzilectMAO-B inhibitor

Indications

Treatment of the signs and symptoms of idiopathic Parkinson's disease as initial monotherapyFDA-labeled
Treatment of the signs and symptoms of idiopathic Parkinson's disease as adjunct therapy to levodopaFDA-labeled

Selective, irreversible inhibitor of monoamine oxidase type B (MAO-B) at recommended clinical doses
Inhibits MAO-B–mediated catabolism of dopamine in the striatum, increasing extracellular dopamine levels and improving parkinsonian motor symptoms
Selectivity for MAO-B over MAO-A diminishes at doses above the recommended range, increasing risk of non-selective MAO inhibition and tyramine-related pressor effects

Monotherapy: 1 mg orally once daily
Adjunct to levodopa: start 0.5 mg once daily; may increase to 1 mg once daily based on clinical response; concurrent levodopa dose reduction may be considered as tolerability allows
Concomitant strong CYP1A2 inhibitors (e.g., ciprofloxacin): limit dose to 0.5 mg once daily due to potential doubling of rasagiline exposure
Requires a washout period of at least 14 days before starting a contraindicated MAOI, opioid, or other interacting serotonergic drug after stopping rasagiline (longer for long-half-life agents such as fluoxetine)

No dosage adjustment required for mild-to-moderate renal impairment; severe renal impairment not systematically studied

Mild hepatic impairment (Child-Pugh 5–6): limit dose to 0.5 mg once daily; moderate-to-severe hepatic impairment is contraindicated

Concomitant use with meperidine or related opioid analgesics (tramadol, methadone, propoxyphene) — risk of serious, potentially fatal serotonin syndrome
Concomitant or recent use of other MAO inhibitors (selective or non-selective, including linezolid and methylene blue) — risk of hypertensive crisis or serotonin syndrome
Concomitant use with dextromethorphan — risk of psychosis or bizarre behavior
Concomitant use with St. John's Wort or cyclobenzaprine
Moderate to severe hepatic impairment

Meperidine and related opioids (tramadol, methadone, propoxyphene): contraindicated — serious/fatal serotonin syndrome
Other MAO inhibitors: contraindicated — hypertensive crisis risk; allow adequate washout before/after use
Antidepressants (SSRIs, SNRIs, tricyclics, tetracyclics): serious CNS toxicity/serotonin syndrome reported — avoid combination; use a 14-day washout (5+ weeks for fluoxetine/fluvoxamine given long half-life) before starting rasagiline or the antidepressant
Dextromethorphan: contraindicated — psychosis/bizarre behavior risk
St. John's Wort and cyclobenzaprine: contraindicated
Sympathomimetic agents (decongestants, stimulants): risk of hypertensive reactions even at recommended MAO-B–selective doses
Strong CYP1A2 inhibitors (e.g., ciprofloxacin): increase rasagiline plasma concentrations — reduce dose to 0.5 mg daily
Dietary tyramine: at recommended doses, rasagiline maintains MAO-B selectivity and dietary tyramine restriction is generally not required, though caution with very high-tyramine foods (e.g., aged cheese) is still advised, particularly if the maximum dose is exceeded
Levodopa: no clinically important pharmacokinetic interaction; some additive dopaminergic adverse effects (e.g., dyskinesia, hypotension) possible

Monotherapy: flu-like syndrome, arthralgia, depression, dyspepsia, headache, falls
Adjunct to levodopa: dyskinesia, accidental injury, weight loss, postural/orthostatic hypotension, nausea, vomiting, constipation, anorexia, rash, abnormal dreams, falls
Orthostatic hypotension, particularly during the first 2 months of treatment
Hypertensive episodes, including rare severe elevations in blood pressure
Hallucinations and new or worsening psychotic behavior
Impulse control disorders and increased libido/hypersexuality reported post-marketing (pathological gambling, compulsive spending, binge eating)
Serotonin syndrome with contraindicated serotonergic combinations
Melanoma risk increased in Parkinson's disease population generally (routine skin surveillance recommended, not specific causality established)

Blood pressure, particularly during the first 2 months of therapy and with dose changes or co-administered sympathomimetics
Signs and symptoms of hypotension (orthostatic) versus hypertensive reactions
Hepatic function, especially in patients with pre-existing mild impairment
Mental status for hallucinations, psychosis, or impulse control symptoms
Motor symptom response (e.g., UPDRS) to guide dosing and levodopa adjustment
Dyskinesia severity when used adjunctively with levodopa
Medication reconciliation for contraindicated opioids, MAOIs, antidepressants, dextromethorphan, and CYP1A2 inhibitors
Routine dermatologic skin examinations

Pregnancy: No adequate human data; animal studies showed decreased offspring survival and reduced body weight at doses substantially exceeding human exposure — use only if potential benefit justifies potential risk to the fetus
Lactation: Rasagiline inhibits prolactin secretion and may reduce milk production; unknown whether rasagiline is excreted in human milk — exercise caution and weigh risks/benefits before breastfeeding