XADAGO

What it is

Xadago contains safinamide (as mesilate) 50 mg or 100 mg per tablet. The tablets are orange to copper, round, biconcave, immediate release, film-coated tablets with metallic gloss. Safinamide is a highly selective and reversible monoamine oxidase B (MAO-B) inhibitor that causes an increase in extracellular levels of dopamine in the striatum, with more than 1000-fold selectivity over MAO-A. Safinamide is also associated with state- and use-dependent inhibition of voltage-gated sodium channels, calcium channel modulation and inhibition of glutamate release.

Approved indications —

Adult patients with fluctuating idiopathic Parkinson's disease as add-on therapy to a regimen that includes levodopa (L-Dopa).

Dosing overview

Xadago treatment should be started at 50 mg per day. The dose may be increased to 100 mg per day after two weeks on the basis of individual clinical need. Xadago may be taken with or without food. Xadago can be used without any dietary tyramine restrictions.

Key safety warnings

Serotonin syndrome has been reported in patients on concomitant treatment with monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, tetracyclic antidepressants, triazolopyridine antidepressants, cyclobenzaprine, opioid drugs and methylphenidate, amphetamine and their derivatives. Symptoms may include mental status changes such as agitation, hallucinations, delirium and coma; autonomic instability such as tachycardia, labile blood pressure, dizziness, diaphoresis, flushing and hyperthermia; neuromuscular symptoms such as tremor, rigidity, myoclonus, hyperreflexia and incoordination; seizures; and gastrointestinal symptoms such as nausea, vomiting and diarrhoea. Safinamide may potentiate the side effects of levodopa and other dopaminergic drugs, and pre-existing dyskinesia may be exacerbated. In clinical studies, dyskinesia was generally mild to moderate in intensity, with very few patients reporting severe dyskinesia and no increase in troublesome dyskinesias. Reducing the patient's daily levodopa dosage or the dosage of another dopaminergic drug may mitigate dyskinesia. Impulse control disorders can occur in patients treated with dopamine agonists and dopaminergic treatments. Safinamide treatment has not been associated with any increase in the appearance of impulse control disorders, however some reports have been observed with other monoamine oxidase inhibitors. Patients and carers should be made aware of behavioural symptoms including compulsions, obsessive thoughts, pathological gambling, increased libido, hyper-sexuality, impulsive behaviour and compulsive spending or buying. Somnolence and dizziness may occur during safinamide treatment. Patients treated with dopaminergic medications have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes has resulted in accidents. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment.

Contraindications

Xadago is contraindicated in patients with hypersensitivity to the active substance or to any of the tablet excipients. Concomitant treatment with other monoamine oxidase inhibitors is contraindicated, with at least 7 days elapsing between discontinuation of safinamide and initiation of treatment with another monoamine oxidase inhibitor. Concomitant treatment with pethidine is contraindicated, with at least 7 days elapsing between discontinuation of safinamide and initiation of treatment with pethidine. Safinamide is contraindicated in patients with severe hepatic impairment. Albinism, retinal degeneration, uveitis, inherited retinopathy or severe progressive diabetic retinopathy are contraindications.

PBS listing

In November 2018, Xadago was recommended for listing on the PBS as a restricted benefit for Parkinson disease as add-on therapy to levodopa in patients experiencing motor fluctuations, with cost-minimisation compared to rasagiline.

Regulatory history

Xadago safinamide 50 mg and 100 mg film-coated tablets were first listed on the ARTG on 2 November 2018. The TGA approved Xadago on 30 October 2018 for the treatment of adult patients with fluctuating idiopathic Parkinson's disease as add-on therapy to a regimen that includes levodopa. The Pharmaceutical Benefits Scheme Advisory Committee recommended the medicine for listing in November 2018.