rasagiline
Brand: Azilect
Prototype: levodopa-carbidopa
Drug Class: monoamine oxidase B inhibitor (MAO-B inhibitor)
Drug Family: antiparkinsonian
Subclass: irreversible selective MAO-B inhibitor
Organ Systems: cns
Mechanism of Action
Irreversibly and selectively inhibits MAO-B, the primary enzyme responsible for dopamine breakdown in the striatum. By preserving striatal dopamine, rasagiline reduces Parkinson's motor symptoms. At therapeutic doses, it is highly selective for MAO-B over MAO-A, avoiding the tyramine interactions of non-selective MAOIs.
MAO-B (monoamine oxidase B)
Indications
- Parkinson's disease (monotherapy early-stage or adjunct to levodopa)
Contraindications
- concurrent non-selective MAOIs
- concurrent meperidine
- concurrent tramadol, methadone, propoxyphene
- concurrent sympathomimetic amines
- concurrent dextromethorphan
- concurrent St. John's wort
Adverse Effects
Common
- headache
- nausea
- orthostatic hypotension
- dyskinesia (when used with levodopa)
- weight loss
Serious
- serotonin syndrome (particularly with serotonergic drugs)
- hypertension (usually mild at therapeutic doses, but possible)
Pharmacokinetics (ADME)
| Absorption | well absorbed orally; bioavailability ~36% (first-pass); food does not significantly affect extent |
| Distribution | protein binding ~88-94% |
| Metabolism | primarily CYP1A2; active metabolite aminoindan (weak MAO-B inhibitor) |
| Excretion | primarily renal |
| Half-life | 3 hours (but enzyme inhibition is irreversible) |
| Onset | enzyme inhibition within hours; clinical Parkinson's effect weeks |
| Peak | 1 hour |
| Duration | irreversible; restored by enzyme synthesis over weeks |
| Protein Binding | 88-94% |
| Vd | not well characterized |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| meperidine | excitatory serotonin syndrome; potentially fatal | contraindicated |
| SSRIs/SNRIs | serotonin syndrome risk via combined serotonergic effect | major |
| CYP1A2 inhibitors (ciprofloxacin, fluvoxamine) | increase rasagiline levels; maximum dose 0.5 mg/day | major |
| sympathomimetics | potential hypertensive reaction (less than non-selective MAOIs) | moderate |
Nursing Considerations
- Rasagiline is MAO-B selective at therapeutic doses and therefore has minimal tyramine dietary interaction; however, excessive tyramine-rich food intake (very aged cheeses, concentrated yeast extracts) should still be moderated.
- Meperidine is absolutely contraindicated; ensure surgical teams are aware of MAO-B inhibitor use before any procedure that may involve opioid administration.
- When used with levodopa, rasagiline may exacerbate dyskinesia due to increased dopamine availability; dose reduction of levodopa may be needed.
- CYP1A2 inhibitors (including ciprofloxacin, a commonly prescribed antibiotic) require dose reduction to rasagiline 0.5 mg/day; verify for antibiotic prescriptions.
Clinical Pearls
- Rasagiline is one of two MAO-B inhibitors used in Parkinson's (the other is selegiline); rasagiline has no amphetamine metabolites (unlike selegiline), making it preferred in patients concerned about stimulant side effects.
- Some clinical data suggest neuroprotective properties of MAO-B inhibitors in PD beyond symptomatic benefit; while not definitively proven, this contributed to their use in early PD monotherapy before levodopa is required.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
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