Drug information of safinamide

safinamide


Safinamide is for the treatment of parkinson's disease .

Mechanism of effect

  • Peak plasma time: 2-3 hr
  • Bioavailability: 95%
  • Steady-state: 3-5 days
  • Protein bound: Not highly protein bound
  • Vd: 165 L
  • Metabolism:Hydrolytic oxidation of the amide moiety leading to the primary metabolite safinamide acid
  • Oxidative cleavage of the ether bond forming O-debenzylatedsafinamide
  • Oxidative cleavage of the amine bond of either safinamide or safinamide acid to form N-dealkylated acid; this is further conjugated with glucuronic acid to yield its acyl glucuronide
  • Half-life: 20-26 hr
  • Total clearance: 4.6 L/hr
  • Excretion: Primarily in urine (~5% unchanged; 76% as inactive metabolites)

Pharmacokinetics

  • Peak plasma time: 2-3 hr
  • Bioavailability: 95%
  • Steady-state: 3-5 days
  • Protein bound: Not highly protein bound
  • Vd: 165 L
  • Metabolism:Hydrolytic oxidation of the amide moiety leading to the primary metabolite safinamide acid
  • Oxidative cleavage of the ether bond forming O-debenzylatedsafinamide
  • Oxidative cleavage of the amine bond of either safinamide or safinamide acid to form N-dealkylated acid; this is further conjugated with glucuronic acid to yield its acyl glucuronide
  • Half-life: 20-26 hr
  • Total clearance: 4.6 L/hr
  • Excretion: Primarily in urine (~5% unchanged; 76% as inactive metabolites)

Drug indications

parkinson

Dosage

Adult

Parkinson Disease

Initial: 50 mg PO qDay

After 2 weeks, may increase dose to 100 mg PO qDay, based on individual need and tolerability

Doses >100 mg/day have not shown additional benefit

Pediatric

Safety and efficacy not established

Drug contraindications

History of hypersensitivity to safinamide; reactions include swelling of the tongue and oral mucosa, and dyspnea
Severe hepatic impairment (Child-Pugh C: 10-15)
Coadministration with other monoamine oxidase inhibitors (MAOIs) or drugs that are potent inhibitors of MAO (eg, linezolid); combination may result in increased blood pressure, including hypertensive crisis
Coadministration with opioids (eg, meperidine and its derivatives, methadone, tramadol); serotonin-norepinephrine reuptake inhibitors (SNRIs); tricyclic, tetracyclic, or triazolopyridine antidepressants; cyclobenzaprine; methylphenidate, amphetamine, and their derivatives; or St John’s wort; combination could result in life-threatening serotonin syndrome
Coadministration with dextromethorphan; combination of MAOIs and dextromethorphan has been reported to cause episodes of psychosis or abnormal behavior

Alerts

May cause or exacerbate hypertension; monitor patients for new onset hypertension or hypertension not adequately controlled after initiating therapy; medication adjustment may be necessary if blood pressure elevation is sustained

May cause serotonin syndrome when used with MAOIs, antidepressants, or opioid drugs (see Contraindications)

May cause falling asleep during activities of daily living

May cause or exacerbate dyskinesia; consider levodopa dose reduction to mitigate dyskinesia

May cause hallucinations and psychotic behavior; consider dosage reduction or stopping medication if patient develops hallucinations or psychotic-like behaviors while on therapy

May cause problems with impulse control/compulsive behaviors; consider dose reduction or stopping medication if a patient develops compulsive behavior while on therapy

May cause withdrawal-emergent hyperpyrexia and confusion

Retinal degeneration and loss of photoreceptor cells observed in animal studies (albino and pigmented rats); periodically monitor patients for visual changes in patients with a history of retinal/macular degeneration, uveitis, inherited retinal conditions, family history of hereditary retinal disease, albinism, retinitis pigmentosa, or any active retinopathy

Points of recommendation

May cause or exacerbate hypertension; monitor patients for new onset hypertension or hypertension not adequately controlled after initiating therapy; medication adjustment may be necessary if blood pressure elevation is sustained

May cause serotonin syndrome when used with MAOIs, antidepressants, or opioid drugs (see Contraindications)

May cause falling asleep during activities of daily living

May cause or exacerbate dyskinesia; consider levodopa dose reduction to mitigate dyskinesia

May cause hallucinations and psychotic behavior; consider dosage reduction or stopping medication if patient develops hallucinations or psychotic-like behaviors while on therapy

May cause problems with impulse control/compulsive behaviors; consider dose reduction or stopping medication if a patient develops compulsive behavior while on therapy

May cause withdrawal-emergent hyperpyrexia and confusion

Retinal degeneration and loss of photoreceptor cells observed in animal studies (albino and pigmented rats); periodically monitor patients for visual changes in patients with a history of retinal/macular degeneration, uveitis, inherited retinal conditions, family history of hereditary retinal disease, albinism, retinitis pigmentosa, or any active retinopathy

Pregnancy level

C


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