Rasagiline

How It Works

Rasagiline is a potent, selective, irreversible inhibitor of monoamine oxidase type B (MAO-B), an enzyme responsible for breaking down dopamine in the brain. By blocking MAO-B, rasagiline increases the availability of dopamine at synapses, providing modest but clinically meaningful symptom improvement. It is used both as monotherapy in early PD and as adjunctive therapy with levodopa in moderate-to-advanced disease.

Typical Dosing

1mg once daily in the morning. No titration needed. Dose reduction to 0.5mg daily if used with CYP1A2 inhibitors (e.g., ciprofloxacin).

Dosing is individualized by the prescribing physician. The information above is for general reference only.

Common Side Effects

• Headache
• Joint pain
• Indigestion
• Flu-like symptoms

Serious Side Effects

Seek medical attention immediately if you experience any of the following:

• Serotonin syndrome (with SSRIs/SNRIs — monitor)
• Hypertensive crisis (with tyramine-rich foods at high doses — less risk than older MAO-Is)

Contraindications

• Concurrent meperidine, tramadol, methadone, or other MAO inhibitors
• Concurrent cyclobenzaprine or St. Johns wort
• Concurrent dextromethorphan

Food Interactions

Mild dietary tyramine restriction is generally not required at the 1mg dose, but avoid excessive amounts of aged cheese, cured meats, and draft beer. The risk of hypertensive crisis is much lower than with older, non-selective MAO inhibitors.

Drug Interactions

The following interactions have been documented with Rasagiline. Always inform your healthcare provider about all medications you are taking.

How Rasagiline Compares to Alternatives

Rasagiline is one of three MAO-B inhibitors available for PD (along with selegiline and safinamide). Compared to selegiline, rasagiline does not produce amphetamine metabolites and requires no dietary restrictions at the standard dose. Compared to safinamide, rasagiline can be used as monotherapy (safinamide is approved only as adjunct to levodopa) but lacks safinamide's additional sodium channel blocking mechanism. All three MAO-B inhibitors are less effective than levodopa for motor symptoms but have favorable tolerability profiles. The 2025 AAN guideline supports MAO-B inhibitors as appropriate first-line therapy when motor symptoms are not significantly affecting quality of life.

When Is Rasagiline Used by Disease Stage?

Early PD (Stages 1-2): Well suited as initial monotherapy when symptoms are mild and not significantly impacting daily function. Simple once-daily dosing with minimal side effects makes it practical for newly diagnosed patients. Mid-stage PD (Stage 2.5-3): Commonly added as adjunct to levodopa to extend its effect and reduce off-time by approximately 1 hour per day. Advanced PD (Stages 4-5): Continued as part of multi-drug regimens but provides only modest additional benefit at this stage. Not typically initiated in advanced disease.

Additional Notes

May be used as monotherapy in early PD or as adjunct to levodopa. The ADAGIO trial (NEJM 2009) explored whether rasagiline might have disease-modifying effects using a delayed-start design — the 1mg dose met the primary endpoint but the 2mg dose did not, leaving the neuroprotection question unresolved. Well tolerated with a favorable side effect profile.