Safinamide

Indications

Safinamide is used for: Parkinson Disease

Adult Dose

Parkinson Disease Indicated as add-on treatment for patients with Parkinson disease who are currently taking levodopa/carbidopa and experiencing “off” episodes Initial: 50 mg PO qDay After 2 weeks, may increase dose to 100 mg PO qDay, based on individual need and tolerability Doses >100 mg/day have not shown additional benefit Hepatic impairment Moderate (Child-Pugh B: 7-9): Not to exceed 50 mg/day Severe (Child-Pugh C: 10-15): Contraindicated

Child Dose

Renal Dose

Administration

May take with or without food

Contra Indications

History of hypersensitivity to safinamide; reactions include swelling of the tongue and oral mucosa, and dyspnea Severe hepatic impairment (Child-Pugh C: 10-15)

Precautions

May cause or exacerbate hypertension; monitor patients for new onset hypertension or hypertension not adequately controlled after initiating therapy; medication adjustment may be necessary if blood pressure elevation is sustained May cause serotonin syndrome when used with MAOIs, antidepressants, or opioid drugs (see Contraindications) May cause falling asleep during activities of daily living May cause or exacerbate dyskinesia; consider levodopa dose reduction to mitigate dyskinesia May cause hallucinations and psychotic behavior; consider dosage reduction or stopping medication if patient develops hallucinations or psychotic-like behaviors while on therapy May cause problems with impulse control/compulsive behaviors; consider dose reduction or stopping medication if a patient develops compulsive behavior while on therapy May cause withdrawal-emergent hyperpyrexia and confusion Retinal degeneration and loss of photoreceptor cells observed in animal studies (albino and pigmented rats); periodically monitor patients for visual changes in patients with a history of retinal/macular degeneration, uveitis, inherited retinal conditions, family history of hereditary retinal disease, albinism, retinitis pigmentosa, or any active retinopathy

Pregnancy-Lactation

Pregnancy There are no adequate and well-controlled studies of safinamide in pregnant women Animal studies Developmental toxicity, including teratogenic effects, was observed when safinamide was administered during pregnancy at clinically relevant doses Developmental toxicity was observed at safinamide doses lower than those used clinically when safinamide was administered during pregnancy in combination with levodopa/carbidopa Lactation Unknown if distributed in human breast milk

Interactions

Coadministration with other monoamine oxidase inhibitors (MAOIs) or drugs that are potent inhibitors of MAO (eg, linezolid); combination may result in increased blood pressure, including hypertensive crisis Coadministration with opioids (eg, meperidine and its derivatives, methadone, tramadol); serotonin-norepinephrine reuptake inhibitors (SNRIs); tricyclic, tetracyclic, or triazolopyridine antidepressants; cyclobenzaprine; methylphenidate, amphetamine, and their derivatives; or St John’s wort; combination could result in life-threatening serotonin syndrome Coadministration with dextromethorphan; combination of MAOIs and dextromethorphan has been reported to cause episodes of psychosis or abnormal behavior

Side Effects

Side effects of Safinamide : >10% Dyskinesia (17-21%) 1-10% Hypertension (5-7%) ALT or AST increased to >ULN (5-7%) Fall (4-6%) Nausea (3-6%) Insomnia (1-4%) Orthostatic hypotension (2%) Anxiety (2%) Cough (2%) Dyspepsia (2%)

Mode of Action

The precise mechanism by which safinamide exerts its effect in PD is unknown Inhibition of MAO-B activity, by blocking the catabolism of dopamine, is thought to result in an increase in dopamine levels and a subsequent increase in dopaminergic activity in the brain