Razeda 1 mg Tablets

RAZEDA is indicated for the treatment of idiopathic Parkinson's disease (PD) as monotherapy (without levodopa) or as adjunct therapy (with levodopa) in patients with end of dose fluctuations.

Posology
The recommended dose of RAZEDA is 1 mg (1 tablet) once daily, with or without levodopa.
Elderly: No change in dose is required for elderly patients.
Children and adolescents (< 18 years): RAZEDA is not recommended as safety and efficacy have not been established in this population.
Patients with hepatic impairment: RAZEDA use in patients with moderate or severe hepatic impairment is contraindicated (see section 4.3). Caution should be used when initiating treatment with RAZEDA in patients with mild hepatic insufficiency. In case patients progress from mild to moderate hepatic impairment RAZEDA should be stopped (see section 4.4).
Patients with renal impairment: No change in dose is required for renal impairment.
Method of administration
For oral use. RAZEDA may be taken with or without food.

• Hypersensitivity to rasagiline or to any of the excipients of RAZEDA, listed in section 6.1.
• Concomitant treatment with other monoamine oxidase (MAO) inhibitors (including products without prescription e.g. St. John's Wort) or pethidine (see section 4.5). At least 14 days must elapse between discontinuation of RAZEDA and initiation of treatment with MAO inhibitors or pethidine.
• Moderate or severe hepatic impairment (Child Pugh B and C).

Concomitant use of RAZEDA with other medicines
The concomitant use of RAZEDA 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 RAZEDA. At least 14 days should elapse between discontinuation of RAZEDA and initiation of treatment with fluoxetine or fluvoxamine.
The concomitant use of RAZEDA and dextromethorphan or sympathomimetics such as those present in nasal and oral decongestants or cold medicines containing ephedrine or pseudoephedrine is not recommended (see section 4.5).
Concomitant use of RAZEDA and levodopa
Since rasagiline as in RAZEDA 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 RAZEDA 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 as in RAZEDA may cause daytime drowsiness, somnolence, and less frequently (especially if used with other dopaminergic medicines) 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 RAZEDA. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines (see section 4.7).

MAO Inhibitors
There are a number of known interactions between non-selective MAO inhibitors and other medicines. RAZEDA should not be administered along with other MAO inhibitors (including medicines and natural products obtained without prescription e.g. St. John's Wort) as there may be a risk of non-selective MAO inhibition that may lead to hypertensive crises (see section 4.3).
Pethidine
Serious adverse reactions have been reported with the concomitant use of pethidine and MAO inhibitors, including another selective MAO-B inhibitor. The concomitant administration of rasagiline as in RAZEDA and pethidine is contraindicated (see section 4.3).
Sympathomimetics
With MAO inhibitors, as well as with another selective MAO-B inhibitor, there have been reports of medicine interactions with the concomitant use of sympathomimetic medicines. Therefore, in view of the MAO inhibitory activity of rasagiline as in RAZEDA, concomitant administration of RAZEDA and sympathomimetics, such as those present in nasal and oral decongestants or cold medicinal products, containing ephedrine or pseudoephedrine, is not recommended (see section 4.4).
Dextromethorphan
There have been reports of medicine interactions with the concomitant use of dextromethorphan and non-selective MAO inhibitors. Therefore, in view of the MAO inhibitory activity of rasagiline as in RAZEDA, the concomitant administration of RAZEDA and dextromethorphan is not recommended (see section 4.4).

Pregnancy
Safety in pregnancy has not been demonstrated.
Breastfeeding
It is not known whether rasagiline is excreted in human milk. Safety in lactation has not been demonstrated.
Fertility
No human data on the effect of rasagiline on fertility are available. Non-clinical data indicate that rasagiline has no effect on fertility.

In patients experiencing somnolence/sudden sleep episodes, rasagiline as in RAZEDA may have a 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 RAZEDA does not affect them adversely. Patients should be cautioned about possible additive effects of sedating medicines, alcohol, or other central nervous system depressants (e.g. benzodiazepines, antipsychotics, antidepressants) in combination with RAZEDA, or when taking concomitant medicines that increase plasma levels of rasagiline (e.g. ciprofloxacin) (see section 4.4).

Summary of the safety profile
In clinical studies in Parkinson's disease patients the most commonly reported adverse reactions were headache, depression, vertigo, and flu (influenza and rhinitis) in monotherapy; dyskinesia, orthostatic hypotension, fall, abdominal pain, nausea and vomiting, and dry mouth in adjunct to levodopa therapy; musculoskeletal pain, as back and neck pain, and arthralgia in both regimens. These adverse reactions were not associated with an elevated rate of medicine discontinuation.

Symptoms
Symptoms reported following overdose of rasagiline as in RAZEDA, in doses ranging from 3 mg to 100 mg included hypomania, hypertensive crisis and serotonin syndrome. Overdose can be associated with significant inhibition of both MAO-A and MAO-B. In a single-dose study healthy volunteers received 20 mg/day and in a ten-day study healthy volunteers received 10 mg/day. Adverse reactions were mild or moderate and not related to rasagiline treatment. In a dose escalation study in patients on chronic levodopa therapy treated with 10 mg/day of rasagiline, there were reports of cardiovascular adverse reactions (including hypertension and postural hypotension) which resolved following treatment discontinuation. These symptoms may resemble those observed with non-selective MAO inhibitors.
Management
There is no specific antidote. In case of overdose, patients should be monitored and the appropriate symptomatic and supportive therapy instituted.