Safinamide for Parkinson’s Disease

Safinamide has recently been added to the Pharmaceutical Benefits Scheme (PBS). It is indicated for the treatment of fluctuating idiopathic Parkinson’s disease as an adjunct to a levodopa-decarboxylase inhibitor combination.

Safinamide is a highly selective and reversible inhibitor of monoamine oxidase B (MAO-B). It works to increase extracellular levels of dopamine in the striatum; a region of the brain responsible for voluntary movement. Safinamide also inhibits the release of glutamate which may have additive benefits for the management of motor complications. Clinical trials demonstrate that safinamide increases daily on time without troublesome dyskinesia by up to 0.55 hours compared to placebo.

The selectivity of safinamide for MAO-B is more than 1,000 times greater than its selectivity for MAO-A. Therefore, dietary tyramine restrictions are not required. However, other medications that inhibit MAO activity must not be used with safinamide. Caution should be exercised when serotonergic agents are used concomitantly; pethidine use is contraindicated. Safinamide may also transiently inhibit the multi-drug transporter known as breast cancer resistance protein (BCRP). At least five hours should be allowed between safinamide doses and BCRP substrates such as pravastatin, ciprofloxacin, methotrexate, topotecan, and diclofenac.

The most common treatment-emergent adverse events reported in clinical trials are dyskinesia, falls, nausea, and insomnia. Retinal degeneration was observed in some animal studies. Although this effect was not reported in human trials, safinamide should be avoided in patients at higher risk of potential retinal effects. Contraindications include albino patients, retinal degeneration, uveitis, inherited retinopathy, and severe progressive diabetic retinopathy.