Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use
Concomitant use of rasagiline with other medicinal products
The concomitant use of rasagiline and fluoxetine or fluvoxamine should be avoided (see section 4.5). At least five weeks should elapse between discontinuation of fluoxetine and initiation of treatment with rasagiline. At least 14 days should elapse between discontinuation of rasagiline and initiation of treatment with fluoxetine or fluvoxamine.

The concomitant use of rasagiline and dextromethorphan or sympathomimetics such as those present in nasal and oral decongestants or cold medicinal product containing ephedrine or pseudoephedrine is not recommended (see section 4.5).

Concomitant use of rasagiline and levodopa
Since rasagiline potentiates the effects of levodopa, the adverse reactions of levodopa may be increased and pre-existing dyskinesia exacerbated. Decreasing the dose of levodopa may ameliorate this adverse reaction.

There have been reports of hypotensive effects when rasagiline is taken concomitantly with levodopa.
Patients with Parkinson’s disease are particularly vulnerable to the adverse reactions of hypotension due to existing gait issues.

Dopaminergic effects
Excessive daytime sleepiness (EDS) and sudden sleep onset (SOS) episodes Rasagiline may cause daytime drowsiness, somnolence, and, occasionally, especially if used with other dopaminergic medicinal products - falling asleep during activities of daily living. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with rasagiline. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines (see section 4.7).

Impulse control disorders (ICDs)
ICDs can occur in patients treated with dopamine agonists and/or dopaminergic treatments. Similar reports of ICDs have also been received post-marketing with rasagiline. Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware of the behavioural symptoms of impulse control disorders that were observed in patients treated with rasagiline, including cases of compulsions, obsessive thoughts, pathological gambling, increased libido, hypersexuality, impulsive behaviour and compulsive spending or buying.

Melanoma
A retrospective cohort study suggested a possibly increased risk of melanoma with the use of rasagiline, especially in patients with longer duration of rasagiline exposure and/or with the higher cumulative dose of rasagiline. Any suspicious skin lesion should be evaluated by a specialist.
Patients should therefore be advised to seek medical review if a new or changing skin lesion is identified.


Hepatic impairment
Caution should be used when initiating treatment with rasagiline in patients with mild hepatic impairment. Rasagiline use in patients with moderate hepatic impairment should be avoided. In case patients progress from mild to moderate hepatic impairment, rasagiline should be stopped (see section 5.2).

Effects on Driving

4.7    Effects on ability to drive and use machines

In patients experiencing somnolence/sudden sleep episodes, rasagiline may have major influence on the ability to drive and use machines.
Patients should be cautioned about operating hazardous machines, including motor vehicles, until they are reasonably certain that rasagiline does not affect them adversely.

Patients being treated with rasagiline and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines) until they have gained sufficient experience with rasagiline and other dopaminergic medications to gauge whether or not it affects their mental and/or motor performance adversely.


If increased somnolence or new episodes of falling asleep during activities of daily living (e.g. watching television, passenger in a car, etc.) are experienced at any time during treatment, the patients should not drive or participate in potentially dangerous activities.
Patients should not drive, operate machinery, or work at heights during treatment if they have previously experienced somnolence and/or have fallen asleep without warning prior to use of rasagiline.

Patients should be cautioned about possible additive effects of sedating medicinal products, alcohol, or other central nervous system depressants (e.g. benzodiazepines, antipsychotics, antidepressants) in combination with rasagiline, or when taking concomitant medications that increase plasma levels of rasagiline (e.g. ciprofloxacin) (see section 4.4).