AZILECT

What it is

AZILECT contains rasagiline mesilate 1 mg and is presented as white to off-white uncoated round tablets. Rasagiline is a potent, irreversible monoamine oxidase type B (MAO-B) selective inhibitor that at the recommended therapeutic dose shows significant inhibition of MAO-B only.

Approved indications —

Symptomatic treatment of idiopathic Parkinson's disease as monotherapy — Symptomatic treatment of idiopathic Parkinson's disease as adjunct therapy to dopamine agonists — Symptomatic treatment of idiopathic Parkinson's disease as adjunct therapy to levodopa

Dosing overview

AZILECT should be administered orally at a dose of 1 mg once daily in both monotherapy and adjunct therapy. It may be taken with or without food. Clinical trials have demonstrated no efficacy advantage for higher doses of rasagiline. When rasagiline is used in combination with levodopa, a reduction of the levodopa dosage may be considered based upon individual response. No change in dosage is required for elderly patients.

Key safety warnings

Severe CNS toxicity associated with hyperpyrexia has been reported with the combined treatment of antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), tricyclic antidepressants, or selective MAO-B inhibitors. These adverse reactions are described as serotonin syndrome, which can result in death. Non-fatal cases of serotonin syndrome have been reported in patients treated with antidepressants concomitantly with AZILECT. Rasagiline is a selective inhibitor of monoamine oxidase (MAO)-B at the recommended doses of 1 mg daily. AZILECT should not be used at daily doses exceeding 1 mg per day because of the risks of hypertensive crisis and other adverse reactions associated with nonselective inhibition of MAO. Certain foods such as aged cheeses may contain very high amounts of tyramine and could potentially cause a hypertensive cheese reaction in patients taking AZILECT even at the recommended doses due to mild increased sensitivity to tyramine. Patients should be advised to avoid foods containing a very large amount of tyramine while taking recommended doses of AZILECT because of the potential for large increases in blood pressure. AZILECT may cause daytime drowsiness, somnolence, and occasionally falling asleep during activities of daily living, especially if used with other dopaminergic medications. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with rasagiline. When used as an adjunct to levodopa, AZILECT may potentiate dopaminergic side effects and may therefore exacerbate pre-existing dyskinesia. Decreasing the dose of levodopa may ameliorate this side effect. Dopaminergic therapy in Parkinson's disease patients has been associated with hallucinations. When used as monotherapy, hallucinations were reported in 1.3 per cent of patients treated with 1 mg AZILECT and 0.7 per cent of placebo patients. When used as an adjunct to levodopa, hallucinations were reported in 2.9 per cent of patients treated with 1 mg per day AZILECT and 2.1 per cent of placebo patients. Impulse control disorders (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 behavioural symptoms of impulse control disorders observed in patients treated with rasagiline, including cases of compulsions, obsessive thoughts, pathological gambling, increased libido, hypersexuality, impulsive behaviour and compulsive spending or buying. A retrospective cohort study showed an increased risk of melanoma in new users of rasagiline treatment compared with new users of non-rasagiline treatment, with a possible increased risk in patients with longer duration of rasagiline exposure and/or higher cumulative dose. Until the melanoma risk associated with Parkinson's disease and/or dopaminergic therapy is better understood, it is recommended that Parkinson's disease patients, including those being treated with AZILECT, should undergo periodic examination of the skin.

Contraindications

AZILECT is contraindicated for use in patients who have demonstrated hypersensitivity to rasagiline or tablet excipients. Concomitant treatment with monoamine oxidase inhibitors (MAOIs) should be avoided. At least 14 days should elapse between discontinuation of rasagiline and initiation of treatment with MAO inhibitors. Concomitant treatment with pethidine should be avoided. At least 14 days should elapse between discontinuation of rasagiline and initiation of treatment with pethidine. Concomitant treatment with tramadol, tapentadol, methadone, dextropropoxyphene, dextromethorphan and St John's wort should be avoided. Concomitant administration of rasagiline with ciprofloxacin and other potent CYP1A2 inhibitors should be avoided. Rasagiline plasma concentration may increase up to 2 and 7 fold in patients with mild and moderate hepatic insufficiency respectively. Therefore, AZILECT should not be used in patients with any degree of hepatic insufficiency.

Regulatory history

AZILECT rasagiline 1 mg tablets were first listed on the ARTG on 6 February 2012.