Safinamide
XADAGO
Pronunciation: sa-FIN-a-mide (ZA-da-goe)
“DA (dopamine) goes (in the) fin safe”
Mao Zedong → MAO inhibitor
What it isReversible MAO-B inhibitor that also blocks sodium channels and glutamate release; Parkinson OFF episodes.
Why this oneThe dual mechanism adds glutamatergic modulation, which the other MAO-B inhibitors lack.
What limits itDyskinesia can worsen. Selectivity is lost at higher doses; avoid with other serotonergic drugs.
Pearls
- Adjunct only; not approved as monotherapy.
- Advantage over rasagiline or selegiline unproven.
- Supratherapeutic doses can cause severe hypertension.
Safinamide prescription history
Animated chart of estimated U.S. prescriptions per year, Parkinson medicines (1948–2026). Safinamide enters in 2017 (estimated).
Principal riskDyskinesia can worsen
Classes and tags
Clinical profile
Legacy pregnancy categoryNot assigned — PLLR-era drug
Defining liabilityOrthostasis, hallucinations, dyskinesia and impulse-control symptoms; abrupt withdrawal can be hazardous.
FDA label
Read the full label on DailyMed ↗
NO BOXED WARNINGS
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Parkinson's disease (adjunct to levodopa/carbidopa, 'off' episodes) | Adults | 50 mg QD | 100 mg QD after 2 weeks | 100 mg QD |
Titration After 2 weeks may increase from 50 mg to 100 mg QD.
Renal Undefined
Hepatic Moderate (Child-Pugh B): max 50 mg QD. Severe (Child-Pugh C): contraindicated.
Instructions
- Take once daily at the same time daily, with or without food
- Effective only in combination with levodopa/carbidopa
- Taper 100 mg to 50 mg for one week before stopping
- If a dose is missed, take the next dose at the usual time the following day
Available strengths
- tab 50, 100 mg
Contraindications
- Concomitant MAO inhibitors or other potent MAO inhibitors, including linezolid (risk of hypertensive crisis)
- Concomitant opioids (meperidine, methadone, propoxyphene, tramadol), SNRIs, tricyclic/tetracyclic/triazolopyridine antidepressants, cyclobenzaprine, methylphenidate, amphetamines, or St. John's wort (risk of serotonin syndrome)
- Concomitant dextromethorphan (risk of psychosis / abnormal behavior)
- Severe hepatic impairment (Child-Pugh C)
Cautions
- Hypertension / hypertensive crisis
- Serotonin syndrome with MAOIs, antidepressants, or opioids
- Falling asleep during activities of daily living
- Dyskinesia (consider levodopa dose reduction)
- Hallucinations / psychotic behavior
- Impulse control / compulsive behaviors
- Withdrawal-emergent hyperpyrexia and confusion
- Retinal pathology
Adverse reactions
- Dyskinesia
- Fall
- Nausea
- Insomnia
Pregnancy No adequate human data; animal studies show developmental toxicity including teratogenicity.
Lactation Undefined
Cost
| Strength | #/mo | generic $/mo | brand $/mo | CostPlus | |
|---|---|---|---|---|---|
| 50 mg | tab | 30 qd | — | $1,093.77 | not offered |
| 100 mg | tab | 30 qd | — | $1,089.77 | not offered |
Generic entry2023
Serotonin and MAOI
Provisional washout figures
Elevating mechanismMAO-B inhibitor; exposure-dependent MAO-A inhibition
Non-elevating actionNone recorded
Exposure dependenceDose-dependent loss of MAO-B selectivity
Washout AFTER an MAOIDose-dependent days
Evidence confidenceModerate
InterpretationSelective MAO-B inhibition at usual doses; MAO-A relevance is dose/exposure dependent.
Open Safinamide in the interactive console ↗
Self-check
- Safinamide: What extra neurotransmitter modulation distinguishes it from other MAO-B inhibitors?
Glutamatergic modulation. - Safinamide: What movement complication can worsen?
Dyskinesia.