Safinamide

SAFINAMIDE

Complete information including dosage, side effects, interactions and pregnancy & breast feeding warnings for patient and professional use

Overview and uses

Safinamide is a medicine used as an add-on treatment for Parkinson’s disease (PD) during ‘off’ episodes.

Indications and uses

  • Safinamide is indicated as an adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing ‘off’ episodes.
  • Safinamide has not shown to be effective as a Monotherapy.

Pharmacological classification

Anti-parkinsonian drug.

Brand names

XADAGO

Dosage form

  • Supplied as film coated tablets in strengths of 50 mg and 100 mg.

Mechanism of action

Safinamide is a selective monoamino oxidase (MAO) B inhibitor, which reduces the degradation of Dopamide. It also inhibits Glutamate release and Dopamine reuptake.

Dosage

  • 50 mg orally once a day at the same time of the day.
  • Safinamide can be taken without any regards to meals.
  • After 2 weeks, dosage can be increased to 100 mg once a day based on individual needs and tolerability.
  • Daily dosage exceeding 100 mg has not been shown to provide additional benefits.
  • In case of a missed dose, next dose should be taken at the same time of the day.
  • Safinamide 100 mg dose should be reduced to 50 mg once a day for 1 week before stopping.

Pediatric dose adjustment

  • Data not available due to insufficient studies.

Geriatric dose adjustment

  • Dose adjustment is not required.
  • Close monitoring of the patient is advisable.

Hepatic dose adjustment

  • For Child-Pugh B (7-9):
    • 50 mg orally once a day.
  • For Child-Pugh C (10-15):
    • Contraindicated in patients with severe hepatic impairment.
  • Safinamide should be discontinued if a patient taking Safinamide progresses from moderate to severe hepatic impairment.

Overdosage

  • No specific antidote is known.
  • General supportive measures should be administered as and when needed.
  • Dietary tyramine restriction should be observed for several weeks.

Side effects

  • Common side effects reported from placebo controlled studies are dyskinesia, fall, nausea and insomnia.
  • Dyskinesia is the most common reported side effect due to withdrawal of Safinamide during clinical trials.
  • Hypertension
    • Safinamide may cause hypertension or it may worsen the existing hypertension.
    • Headaches, anxiety, shortness of breath and nose bleed are some of the symptoms.
    • Consult your doctor as soon as possible as this may require a dose reduction of Safinamide.
  • Serotonin syndrome
    • Potentially life threatening serotonin syndrome has been reported in patients concomitantly taking Safinamide and mono amino oxidase inhibitors.
    • Symptoms of serotonin syndrome include change in mental status (agitation, hallucination, delirium and coma), autonomic instability (tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures and/or gastrointestinal symptoms (nausea, vomiting and diarrhea).
    • Consult your doctor as soon as possible. This may be life threatening.
  • Falling asleep during activities of daily living
    • Sleep attacks or sudden onset of sleep has been reported in patients taking Safinamide 100 mg in clinical trials.
    • If a patient develops day time sleepiness or episodes of falling asleep, than such patients should be advised to avoid activities that requires full attention. E.g., driving.
  • Dyskinesia
    • Safinamide may cause dyskinesia or it may worsen the pre-existing dyskinesia.
    • Reducing the daily dose of levodopa or other dopaminergic drug may mitigate dyskinesia.
  • Hallucinations/psychotic behavior
    • Safinamide should be avoided in patients with a major psychotic disorder as Safinamide may worsen the psychosis with an increase in central dopaminergic tone.
    • Also, treatment for psychosis antagonizes the effects of dopaminergic medications. This may exacerbate the symptoms of Parkinson’s disease.
    • Consider dose reduction or discontinuation of Safinamide if a patient develops hallucinations or psychotic – like behavior.
  • Impulse control/compulsive behavior
    • Patients taking Safinamide may experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating and/or other intense urges and the inability to control these urges.
    • Since patients will not consider this behavior as abnormal, it is advisable that the prescriber specifically ask the patient or their care givers about the new or increased urges that are mentioned above.
    • Consider dose reduction or discontinuation of the medicine.
  • Withdrawal emergent hyperpyrexia and confusion
    • This has been reported with rapid dose reduction, sudden withdrawal or changes in drugs that increase central dopaminergic tone.
    • Elevated temperature, muscular rigidity, altered consciousness and autonomic instability are the symptoms.
  • Retinal pathology
    • Retinal degeneration and loss of photoreceptor cells has been reported in animal studies.
    • 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.
  • Side effects reported from the post marketing experience
    • A post marketing report describes a hypersensitivity reaction consisting of:
      • Swelling of tongue and gums.
      • Dyspnea and skin rash.

Pregnancy and breast feeding warnings

Pregnancy

  • Category C, which means animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Nursing mothers

  • It is not known whether Safinamide is excreted in human breast milk or not.
  • Since many drugs are excreted in milk and because of the potential for side effects in nursing infants, a decision should be made whether to discontinue drug or to discontinue nursing.

Interactions

Drug-drug interactions

  • Mono Amino Oxidase (MAO) inhibitors
    • Co-administration of MAO inhibitors or any other drug that inhibits MAO, with Safinamide may lead to Hypertensive crisis.
    • At least 14 days should elapse between discontinuation of Safinamide and initiation of treatment with MAO inhibitors.
    • Linezolid, Isoniazid, Selegiline, Isocarboxazid, Tranylcypromine, Phenelzine are some of the examples of the drugs that causes MOA inhibition.
  • Opioid drugs
    • Serious and fatal reactions have been reported with concomitant use of Opioid drugs with Safinamide.
    • At least 14 days should elapse between discontinuation of Safinamide and initiation of treatment with MAO inhibitors.
  • Serotonergic drugs
    • Concomitant use of Safinamide with serotonergic drugs is contraindicated as it may cause serotonin syndrome.
    • At least 14 days should elapse between discontinuation of Safinamide and initiation of treatment with MAO inhibitors.
    • Monitor patients for the symptoms of serotonin syndrome if a patient treated with Safinamide has taken selective serotonin reuptake inhibitors.
    • Triazolopyridine, tricyclic or tetracyclic anti depressant, cyclobenzaprine, St. John’s wart are some of the examples of serotonergic drugs.
  • Dextromethorphan
    • Safinamide possesses MAO inhibitory actions.
    • Concomitant use of Safinamide with Detromethorphan has been reported to cause psychosis or bizarre behavior.
  • Sympathomimetic drugs
    • Methylphenidate, amphetamine and its derivatives are some of the examples of sympathomimetic drugs.
    • Safinamide possesses MAO inhibitory actions.
    • Severe hypertension has been reported with co-administration of Safinamide with MAO inhibitors.
  • Tyramine
    • MAO in the gastrointestinal tract and liver (primarily type A) provides protection from exogenous amines (e.g., tyramine).
    • If tyramine were absorbed intact, it could lead to severe hypertension, including hypertensive crisis. Aged, fermented, cured, smoked, and pickled foods containing large amounts of exogenous amines (e.g., aged cheese, pickled herring) may cause release of norepinephrine resulting in a rise in blood pressure (Tyramine Reaction).
    • Patients should be advised to avoid foods containing a large amount of tyramine while being treated with Safinamide.
  • Substrates for breast cancer resistance protein
    • Safinamide and its major metabolite may inhibit intestinal BCRP (breast cancer resistance protein). Inhibition of BCRP could increase plasma concentrations of BCRP substrates.
    • Methotrexate, Mitoxantrone, Imatinib, Irrinotecan, Lapatinib, Rosuvastatin, Sulfasalazine, topotecan are some of the examples of drugs that causes BCRP inhibition.
  • Dopaminergic antagonists
    • Concomitant use of dopaminergic drugs with Safinamide may decrease the effectiveness of Safinamide and exacerbate the symptoms of Parkinson’s disease.
    • Antipsychotics, metochlopromide are some of the examples.

Drug food interaction

  • Avoid food that is rich in tyramine.

Click here to go to Safinamide (Xadago) forums.

Reference:

  • “Product information. XADAGO® (Safinamide).” US Worldmeds, LLC, KY-40241.

 

By |2018-12-29T07:32:45+00:00April 26th, 2017|medicines|Comments Off on Safinamide

About the Author:

B. Pharm (K.L.E. society's S.V.V. Patil College of Pharmacy, Bengaluru) M. Pharm (Maharishi Arvind Institute of Pharmacy, Jaipur)

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