Safinamide

Oral
Parkinson's disease

Moderate (Child-Pugh class B): Max: 50 mg once daily. Severe (Child-Pugh class C): Contraindicated.

Albinism, retinal degeneration, uveitis, inherited retinopathy or severe progressive diabetic retinopathy. Severe hepatic impairment (Child-Pugh class C). Concomitant use with or within 2 weeks of other MAOIs or other drugs that are potent inhibitors of monoamine oxidase (including linezolid), opioids, SNRIs, TCAs, tetracyclic or triazolopyridine antidepressants, cyclobenzaprine or St. John's wort. Concomitant use with methylphenidate, amphetamine and their derivatives or dextromethorphan.

Patient with major psychotic disorder, other ophthalmic disorders. Avoid abrupt withdrawal. Moderate hepatic impairment (Child-Pugh class B). Pregnancy and lactation.

Significant: New-onset or worsening hypertension, CNS depression, dyskinesia, impulse control disorders; withdrawal-emergent hyperpyrexia and confusion (upon abrupt discontinuation or interruption of therapy); retinal disorder.
Blood and lymphatic system disorders: Anaemia, leucopenia, RBC abnormality.
Cardiac disorders: Palpitations, tachycardia, sinus bradycardia, arrhythmia.
Ear and labyrinth disorders: Vertigo.
Eye disorders: Cataract.
Gastrointestinal disorders: Nausea, dyspepsia.
Injury, poisoning and procedural complications: Fall.
Investigations: Increased ALT or AST.
Metabolism and nutrition disorders: Decreased or increased appetite.
Nervous system disorders: Dizziness, headache.
Psychiatric disorders: Insomnia, depression, restlessness.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, rhinorrhoea.
Vascular disorders: Orthostatic hypotension.

PO: C

This drug may cause dizziness or falling asleep during activities that require full attention; if affected, do not drive or operate machinery.

Monitor blood pressure (at baseline, periodically, and as needed); hepatic function. Assess for signs and symptoms of visual changes, serotonin syndrome, new-onset or worsening hypertension and dyskinesia.

Symptoms: Confusion, sleepiness, forgetfulness, dilated pupils, nausea, vomiting, hallucinations, agitation, hypertension, postural hypotension and dyskinesia. Management: Supportive treatment.

Increased risk of hypertension with isoniazid, sympathomimetic agents (including nasal, oral or ophthalmic decongestants). Concurrent use with antipsychotics or metoclopramide may decrease the effectiveness of safinamide. May increase plasma concentrations of BCRP substrates (e.g. methotrexate, irinotecan, topotecan, imatinib, rosuvastatin).
Potentially Fatal: Increased risk of hypertensive crisis with other MAOIs (e.g. selegiline, rasagiline) or other drugs that are potent inhibitors of monoamine oxidase (including linezolid). Increased risk of serotonin syndrome with opioids (e.g. tramadol, methadone, propoxyphene, pethidine and its derivatives), SNRIs (e.g. duloxetine, venlafaxine), SSRIs (e.g. fluoxetine, fluvoxamine), TCAs (e.g. amitriptyline, imipramine), tetracyclic antidepressants (e.g. maprotiline, mianserin), cyclobenzaprine, methylphenidate, amphetamine and their derivatives. Concomitant use with dextromethorphan may cause psychosis or abnormal behaviour.

Increased risk of serotonin syndrome with St. John's wort. Increased risk of hypertensive crisis when concurrently taken with tyramine-rich foods.

Description:
Mechanism of Action: Safinamide, an α-aminoamide derivative, is a highly selective and reversible monoamine oxidase type B (MAO-B) inhibitor. It blocks the catabolism of dopamine which results in increased dopamine levels and consequently increases the dopaminergic activity of the brain.
Pharmacokinetics:
Absorption: Rapidly absorbed. Bioavailability: 95%. Time to peak plasma concentration: 2-3 hours.
Distribution: Plasma protein binding: 88-90%.
Metabolism: Primarily metabolised by non-microsomal enzymes (cytosolic amidases or MAO-A) into inactive metabolites and minimally metabolised by CYP3A4 and other CYP isoenzymes.
Excretion: Mainly via urine (76% primarily as inactive metabolites; approx 5% as unchanged drug). Elimination half-life: 20-26 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 131682, Safinamide. https://pubchem.ncbi.nlm.nih.gov/compound/Safinamide. Accessed Nov. 21, 2023.

Store between 15-30°C.

Antiparkinsonian Drugs

N04BD03 - safinamide ; Belongs to the class of dopaminergic agents, monoamine oxidase B inhibitors. Used in the management of Parkinson's disease.

Anon. Safinamide Mesylate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/10/2023.

Anon. Safinamide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/10/2023.

Buckingham R (ed). Safinamide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/10/2023.

Equfina 50 mg Film-coated tablet (Meiji Seika Pharma Co., Ltd.). MIMS Philippines. http://www.mims.com/philippines. Accessed 02/10/2023.

Equfina Tablets 50 mg (Bora Pharmaceuticals Co., Ltd.). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 13/11/2023.

Joint Formulary Committee. Safinamide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/10/2023.

Xadago 100 mg Film-coated Tablets (Zambon S.p.A.). MHRA. https://products.mhra.gov.uk. Accessed 02/10/2023.

Xadago Tablet, Film Coated (MDD US Operations LLC, a subsidiary of Supernus Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/10/2023.