Safinamide

Oral
Parkinson's disease
Adult: As add-on therapy to levodopa alone or in combination with other antiparkinsonian drugs in mid- to late-stage fluctuating patients: Initially, 50 mg once daily; may increase to 100 mg daily based on patient's response and tolerability. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Hepatic impairment: 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. Patient Counselling This drug may cause dizziness or falling asleep during activities that require full attention; if affected, do not drive or operate machinery. Monitoring Parameters 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.

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.

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.

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.
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.

Oral: Store between 15-30°C.

Antiparkinsonian Drugs

N04BD03 - safinamide ; NULL