General

Pronunciation:
sa-fin-a-mide

Trade Name(s)

• Xadago

Ther. Class.

antiparkinson agents

Pharm. Class.

monoamine oxidase type B inhibitors

Indications

Adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease (PD) who are experiencing "off" episodes.

Action

Irreversibly inhibits monoamine oxidase (MAO) B, which leads to ↑ dopamine levels in the CNS.

Therapeutic Effect(s):

Increased amount of "on" time without dyskinesia or with non-troublesome dyskinesia.

Pharmacokinetics

Absorption: 95% absorbed following oral administration.

Distribution: Extensively distributed to the tissues; readily crosses the blood-brain barrier.

Metabolism and Excretion: Extensively metabolized by hydrolytic oxidation or oxidative cleavage to inactive metabolites; 76% excreted in urine (primarily as inactive metabolites).

Half-life: 20–26 hr.

TIME/ACTION PROFILE (blood levels)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Concurrent use of other MAO inhibitors;
• Concurrent use of opioids, SNRIs, TCAs, cyclobenzaprine, methylphenidate, amphetamine, or St. John's wort;
• Concurrent use of dextromethorphan;
• Severe hepatic impairment (Child-Pugh C);
• Psychotic disorder;
• Lactation:  Discontinue breast feeding or discontinue the safinamide.

Use Cautiously in:

• Retinal disease;
• Moderate hepatic impairment (Child-Pugh B) (do not exceed maximum recommended dose);
• OB:  Use only if maternal benefit outweighs fetal risk;
• Pedi:  Safety and effectiveness not established.

Adverse Reactions/Side Effects

CV: hypertension, orthostatic hypotension

EENT: visual changes

GI: ↑ liver enzymes, nausea

Neuro: dyskinesia, paresthesia, anxiety, drowsiness, hallucinations, impulse control disorders (gambling, sexual, binge eating), ↑ fall risk, insomnia, psychosis, sleep attacks, sleep driving

Resp: cough

Misc: hypersensitivity reactions

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• Concurrent use of other  MAO inhibitors, including  linezolid  and  isoniazid, may ↑ risk of hypertensive crises and is contraindicated; separate administration by ≥14 days.

• Concurrent use of  meperidine,  methadone,  tramadol,  SNRIs,  TCAs,  cyclobenzaprine,  methylphenidate, or  amphetamine  may ↑ risk of serotonin syndrome and is contraindicated; separate administration by ≥14 days; SSRIs may be used at the lowest dose possible.

• Concurrent use with  dextromethorphan  may result in psychosis/bizarre behavior and is contraindicated.

• Hypertensive crisis may occur with cough and cold products containing  sympathomimetic amines  including  pseudoephedrine  and  phenylephrine ; monitor patient's BP closely.
• May ↑ levels/toxicity of  imatinib,  irinotecan,  lapatinib,  methotrexate,  mitoxantrone,  rosuvastatin,  sulfasalazine, and  topotecan ; monitor closely for adverse effects.
•  Dopamine antagonists, including  antipsychotics  and  metoclopramide  may ↓ effectiveness of safinamide.

Drug-Natural Products:

Concurrent use with  St. John's wort  may ↑ risk of serotonin syndrome; concurrent use contraindicated.

Drug-Food:

Ingestion of foods containing high amounts of tyramine (>150 mg) (e.g., cheese) may result in hypertensive crisis.

Route/Dosage

PO (Adults): 50 mg once daily; after 2 wk, may ↑ dose to 100 mg once daily.

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment (Child-Pugh B)– Do not exceed 50 mg/day;  Severe hepatic impairment (Child-Pugh C)– Contraindicated.

Availability

Tablets: 50 mg, 100 mg

Assessment

• Assess signs and symptoms of Parkinson's disease (tremor, muscle weakness and rigidity, ataxic gait) prior to and during therapy.
• Monitor for new-onset hypertension or hypertension not adequately controlled after starting safinamide. Sustained BP elevation may require dose reduction.

• Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).

Toxicity and Overdose:

Concurrent ingestion of tyramine-rich foods and many medications may result in a life-threatening hypertensive crisis. Signs and symptoms of hypertensive crisis include chest pain, tachycardia or bradycardia, severe headache, neck stiffness or soreness, nausea and vomiting, sweating, photosensitivity, and enlarged pupils.

Potential Diagnoses

• Impaired physical mobility (Indications) 
• Risk for injury (Indications)  (Side Effects) 

Implementation

• PO Administer once daily, at the same time each day, without regard to food.

Patient/Family Teaching

• Instruct patient to take safinamide as directed. Missed doses should be omitted and next dose taken at usual time the following day. Do not double doses. Do not discontinue abruptly; may cause elevated temperature, muscular rigidity, altered consciousness, and autonomic instability. Advise patient to read  Patient Information  before starting therapy and with each Rx refill in case of changes.

• Caution patient to avoid alcohol, CNS depressants, and foods or beverages containing tyramine (see food sources for specific nutrients) during and for at least 2 wk after therapy has been discontinued; they may precipitate a hypertensive crisis. Contact health care professional immediately if symptoms of hypertensive crisis or serotonin syndrome develop.

• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications. Caution patient to avoid use of St. John's wort, cough or cold products containing dextromethorphan, and analgesics meperidine, tramadol, or methadone during therapy.

• May cause drowsiness and unexpected episodes of falling asleep. Caution patient to avoid driving or other activities requiring alertness until response to medication is known. Advise patient to notify health care professional if episodes of falling asleep occur.

• Advise patient to notify health care professional if new or increased gambling, sexual, or other impulse control disorders or psychotic-like behaviors occur.
• Advise female patients to notify health care professionals if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

Improvement in symptoms of Parkinson's disease, allowing increase in function.