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.
FDA label
Read the full label on DailyMed ↗
| 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 each day, 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
NO BOXED WARNINGS
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.
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.