Rasagiline

May cause new or worsening mental status and behavioral changes, which may be severe, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium after starting or increasing the dose of rasagiline. Intense urges to gamble or spend money, increased sexual urges, binge eating, and/or other intense urges, as well as the inability to control these urges, have also been reported. Monitor for these symptoms. If symptoms develop, consider dose reduction or discontinue of therapy.

Dyskinesia, exacerbation of preexisting dyskinesia, or increased dopaminergic side effects may occur when used as an adjunct to levodopa. Decreasing the dose of levodopa may mitigate these side effects.

May cause exacerbation of hypertension; monitor for new onset hypertension or hypertension not adequately controlled after starting rasagiline. Medication adjustment may be necessary if blood pressure elevation is sustained.

Risk of melanoma may be increased with rasagiline, although increased risk has been associated with Parkinson’s disease itself; patients should have regular and frequent skin examinations.

May cause orthostatic hypotension, particularly in combination with levodopa. Orthostatic hypotension occurs most frequently during the first 2 months of therapy and decreases over time.

Serotonin syndrome (SS) has been reported with concomitant antidepressant (eg, SSRI, SNRI, TCA, tetracyclic and triazolopyridine antidepressants) use; concomitant use is not recommended within 14 days of rasagiline administration (within 5 weeks for antidepressants with long half-lives such as fluoxetine). SS has also been reported with concomitant use of MAO inhibitors (including selective MAO-B inhibitors), meperidine, methadone, propoxyphene, and tramadol; concomitant use within 14 days of rasagiline administration is contraindicated. A symptom complex resembling neuroleptic malignant syndrome (NMS) has been reported in association with rapid dose reduction, withdrawal of, or changes in drugs that increase central dopaminergic tone. Identification and differentiation of SS (eg, tremor, myoclonus, agitation) and more severe NMS-like reactions (eg, hyperthermia, muscle rigidity, autonomic instability, mental status changes) can be complex; monitor patients closely for either syndrome. The diagnosis of SS can be made using the Hunter Serotonin Toxicity Criteria (Dunkley, 2003). Discontinue treatment (and any concomitant antidepressants) immediately if signs/symptoms arise.

Somnolence and falling asleep while engaged in activities of daily living (including operation of motor vehicles) have been reported; some cases reported that there were no warning signs for the onset of symptoms. Symptom onset may occur well after initiation of treatment; some events have occurred >1 year after initiation of rasagiline. Prior to treatment initiation, evaluate for factors that may increase these risks such as concomitant sedating medications, the presence of sleep disorders, and concomitant medications that increase rasagiline plasma levels (eg, ciprofloxacin). Monitor for drowsiness or sleepiness. If significant daytime sleepiness or episodes of falling asleep during activities that require active participation occur (eg, driving, conversations, eating), discontinue rasagiline. There is insufficient information to suggest that dose reductions will eliminate these symptoms. If therapy is continued, advise patient to avoid driving and other potentially dangerous activities. Disease-related concerns:

Use with caution in patients with mild hepatic impairment; dose reduction recommended. Avoid use in patients with moderate-to-severe impairment.

Avoidance of use is recommended in patients with major psychotic disorder due to the risk of exacerbating psychosis with an increase in central dopaminergic tone. Many treatments for psychosis that decrease central dopaminergic tone may also decrease the effectiveness of rasagiline. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

According to many of the MOA inhibitor manufacturers, use within 10 days prior to elective surgery is contraindicated. The decision to continue or withhold MAO inhibitors must be done in collaboration with the patient's psychiatrist. Currently, an MAO-safe anesthetic technique which excludes the use of meperidine and indirect-acting adrenergic agonists is recommended for patients requiring continued MAO inhibitor therapy (Huyse, 2006). Other warnings/precautions:

In patients taking recommended doses of rasagiline, dietary restriction of most tyramine-containing products is not necessary; however, certain foods (eg, aged cheeses) may contain high amounts (>150 mg) of tyramine and could lead to hypertensive crisis. Avoid concomitant use with foods high in tyramine. Rasagiline is a selective inhibitor of MAO-B at the recommended doses; however, MAO-B selectivity diminishes in a dose-related manner above the recommended daily doses.