Safinamide

Safinamide is used to treat Parkinson's Disease.

Safinamide is available under the following different brand names: Xadago.

Dosage Forms and Strengths

Tablet

• 50 mg
• 100 mg

Dosage Considerations – Should be Given as Follows:

Parkinson's Disease

• Indicated as add-on treatment for patients with Parkinson disease who are currently taking levodopa/carbidopa and experiencing "off" episodes
• Initial: 50 mg orally once daily
• After 2 weeks, may increase dose to 100 mg orally once daily, based on individual need and tolerability
• Doses greater than 100 mg/day have not shown additional benefit

Dosage Modifications

Liver Impairment

• Moderate (Child-Pugh B: 7-9): Not to exceed 50 mg/day
• Severe (Child-Pugh C: 10-15): Contraindicated

Dosing Considerations

• Limitation of use: Not shown effective as monotherapy for Parkinson's Disease
• Safety and efficacy not established in pediatric patients

Side effects of Safinamide include:

• Involuntary muscle movements
• High blood pressure (hypertension)
• ALT or AST increased to greater than ULN
• Fall
• Nausea
• Insomnia
• Dizziness on standing
• Anxiety
• Cough
• Heartburn/indigestion

Postmarketing side effects of safinamide reported include:

• Swelling of tongue and gums
• Shortness of breath
• Rash

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Safinamide has severe interactions with at least 48 different drugs.
• Safinamide has serious interactions with at least 30 different drugs.
• Safinamide has moderate interactions with at least 63 different drugs.
• Safinamide has no listed mild interactions with other drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

This medication contains safinamide. Do not take Xadago if you are allergic to safinamide or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

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 (e.g., linezolid); combination may result in increased blood pressure, including hypertensive crisis
• Coadministration with opioids (e.g., 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

Effects of Drug Abuse

• No information available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Safinamide?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Safinamide?"

Cautions

• 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 monoamine oxidase inhibitors (MAOIs), antidepressants, or opioid drugs
• 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

Drug interaction overview

• Safinamide is contraindicated with other drugs in the MAOI class or other drugs that are potent inhibitors of MAO
• Opioids combined with safinamide has caused serious and sometimes fatal reactions and is contraindicated; at least 14 days should elapse between use of safinamide and these drugs to avoid serotonin syndrome
• Dextromethorphan and MAOIs is contraindicated, owing to reports of psychosis or bizarre behavior
• Isoniazid has some monoamine oxidase inhibiting activity; monitor for hypertension and reaction to dietary tyramine in patients treated concomitantly with isoniazid
• Safinamide and its major metabolite may inhibit intestinal breast cancer resistance protein (BCRP), and therefore could increase plasma concentrations of BCRP substrates (e.g., methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan)
• Dopamine antagonists, such as antipsychotics or metoclopramide, may decrease the effectiveness therapy and exacerbate the symptoms of Parkinson's disease
• Sympathomimetics
  • Severe hypertensive reactions have followed administration of sympathomimetics and nonselective MAOIs
  • Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications
  • Concomitant use with methylphenidate, amphetamine, and their derivatives is contraindicated; monitor patients for hypertension if therapy is prescribed concomitantly with prescription or nonprescription sympathomimetic medications, including nasal, oral, or ophthalmic decongestants and cold remedies
• Serotonergic drugs
  • SNRIs; triazolopyridine, tricyclic, or tetracyclic antidepressants; cyclobenzaprine; or St John's wort are contraindicated with safinamide; at least 14 days should elapse between use of safinamide and these drugs to avoid serotonin syndrome
  • Coadministration with SSRIs: Monitor for symptoms of serotonin syndrome
• Tyramine
  • MAO in the GI 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)
  • Advise patients to avoid foods containing large amounts of tyramine
  • Selectivity for inhibiting MAO-B decreases in a dose-related manner above the highest recommended daily dosage, which may increase the risk for hypertension
  • In addition, isoniazid has some MAO inhibiting activity; monitor for hypertension and reaction to dietary tyramine in patients treated with isoniazid and safinamide

Pregnancy and Lactation

There are no adequate and well-controlled studies of safinamide in pregnant women. In animal studies, developmental toxicity, including teratogenic effects, was observed when safinamide was administered during pregnancy at clinically relevant doses. In animal studies, developmental toxicity was observed at safinamide doses lower than those used clinically when safinamide was administered during pregnancy in combination with levodopa/carbidopa. Consult your doctor.

It is unknown if safinamide is distributed in human breast milk. In rats, skin discoloration, presumed to be caused by hyperbilirubinemia resulting from hepatobiliary toxicity, was observed in rat pups indirectly exposed to safinamide through the milk during the lactation period. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.