Safinamide

Uses

Safinamide is a MAO-B inhibitor used as an add-on treatment to levodopa/carbidopa for Parkinson's disease during "off" episodes.

Safinamide is indicated as an add-on treatment to levodopa with or without other medicines for Parkinson’s disease

Safinamide is also used to associated treatment for these conditions: Parkinson's Disease (PD)

How Safinamide works

Safinamide is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide has neuroprotective and neurorescuing effects in MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model.

Toxicity

uncontrolled involuntary movement, falls, nausea, and trouble sleeping or falling asleep (insomnia) Patients who have an overdose may experience hypertension (high blood pressure), orthostatic hypotension, hallucinations, psychomotor agitation, nausea, vomiting, and dyskinesia.

Food Interaction

• Avoid excessive or chronic alcohol consumption. Ingesting alcohol may increase the sedative effects of safinamide.
• Avoid St. John's Wort. This herb may increase the risk of serotonin syndrome, and therefore, concomitant use is contraindicated.
• Avoid tyramine-containing foods and supplements. Avoid foods containing high amounts of tyramine (>150mg) as these foods may cause a significant elevation in blood pressure. Tyramine-containing foods include cheese, red wine, fava beans, pickled food, cured food, and alcoholic beverages.
• Take at the same time every day.
• Take with or without food.

[Major] GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase inhibitors (MAOIs).

The mechanism is inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact.

Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules.

Although safinamide is considered a selective inhibitor of MAO-B, the selectivity may not be absolute even at recommended dosages.

Hypertensive reactions have not been reported with safinamide; however, rare cases of hypertensive reactions associated with ingestion of tyramine-containing foods have been reported in patients taking the recommended daily oral dose of selegiline, another selective inhibitor of MAO-B.

MANAGEMENT: Patients treated with safinamide should avoid consumption of products that contain large amounts of amines and protein foods in which aging or breakdown of protein is used to increase flavor.

These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, salamis, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, sauerkraut, yogurt, papaya products, meat tenderizers, fava bean pods, protein extracts, yeast extracts, and dietary supplements.

Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well.

At least 14 days should elapse following discontinuation of safinamide therapy before these foods may be consumed.

Specially designed reference materials and dietary consultation are recommended so that an appropriate and safe diet can be planned.

Patients should also be advised to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, difficulty thinking, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms.

The recommended dosages of safinamide should not be exceeded, as it can increase the risk of nonselective MAO inhibition and a hypertensive crisis.

Safinamide Alcohol interaction

[Moderate] GENERALLY AVOID:

Alcohol may potentiate some of the pharmacologic effects of central nervous system (CNS)-active agents.

Use in combination may result in additive CNS depression and/or impairment of judgment, thinking, and psychomotor skills.

Patients receiving CNS-active agents should be advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled against driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Safinamide Hypertension interaction

[Moderate] Safinamide may cause hypertension or exacerbate existing hypertension.

Patients should be monitored for new onset hypertension or hypertension that is not adequately controlled after starting treatment.

Dosage adjustment may be necessary if elevation of blood pressure is sustained.

Safinamide Drug Interaction

Moderate: metoprolol, rotigotine, carbidopa / levodopa, carbidopa / levodopa, carbidopa / entacapone / levodopa, valerianUnknown: rasagiline, rivastigmine, apomorphine, linaclotide, esomeprazole, omega-3 polyunsaturated fatty acids, acetaminophen, clopidogrel, eletriptan, omega-3 polyunsaturated fatty acids, levothyroxine, multivitamin, cholecalciferol

Safinamide Disease Interaction

Major: hypotension, psychosis, hepatic impairmentModerate: hypertension, retinal pathology

Volume of Distribution

1.8 litres/kg

Elimination Route

Rapid with peak plasma concentrations ranging from 2 to 4 h, total bioavailability is 95%. Food prolonged the rate and did not affect the extent of absorption of safinamide.

Half Life

22 h

Clearance

total oral clearance of plasma , which accounts for parent safinamide as well as metabolites, was on average only 17.53 ± 2.71 ml/h × kg

Elimination Route

76% renal, 1.5% faeces

Innovators Monograph

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