Safinamide

Name: Safinamide

Why is this medication prescribed?

Safinamide is used along with the combination of levodopa and carbidopa (Duopa, Rytary, Sinemet, others) to treat ''off'' episodes (times of difficulty moving, walking, and speaking that may happen as medication wears off or at random) in people with Parkinson's disease (PD; a disorder of the nervous system that causes difficulties with movement, muscle control, and balance). Safinamide is in a group of medications called monoamine oxidase type B (MAO-B) inhibitors. It works by increasing the amount of dopamine (a natural substance that is needed to control movement) in the brain.

What special precautions should I follow?

Before taking safinamide,

  • tell your doctor and pharmacist if you are allergic to safinamide (mouth or tongue swelling, shortness of breath), any other medications, or any of the ingredients in safinamide tablets. Ask your pharmacist for a list of the ingredients.
  • tell your doctor if you are taking any of the following: amphetamines (stimulants, 'uppers') such as amphetamine (Adderall, Adzenys, Dyanavel XR, in Adderall), dextroamphetamine (Dexedrine, in Adderall), and methamphetamine (Desoxyn); certain antidepressants such as amitriptyline (Elavil), amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), mirtazapine (Remeron) and trazodone; buspirone; cyclobenzaprine (Amrix); methylphenidate (Aptensio, Metadate, Ritalin, others); opioids such as meperidine (Demerol), methadone (Dolophine, Methadose), propoxyphene (no longer available in U.S.; Darvon), or tramadol (Conzip, Ultram, in Ultracet); selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) such as duloxetine (Cymbalta) and venlafaxine (Effexor); and St. John's wort; Also tell your doctor if you are taking an MAO inhibitor such as isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate).or have stopped taking them within the past two weeks. Your doctor will probably tell you that you should not take safinamide along with any of these medications. If you stop taking safinamide, you should wait at least 14 days before you start to take any of these medications. Also, do not take dextromethorphan (in Robitussin DM; found in many nonprescription cough and cold products) along with safinamide.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: antipsychotics such as clozapine (Clozaril, Fazaclo, Versacloz) and olanzapine (Zyprexa); benzodiazepines such as alprazolam (Xanax), diazepam (Diastat, Valium), lorazepam (Ativan), temazepam (Restoril), and triazolam (Halcion); medications for colds and allergies (decongestants) including those placed in the eye or nose; imatinib (Gleevec); irinotecan (Camptosar, Onivyde); isoniazid (Laniazid, in Rifamate, in Rifater); lapatinib (Tykerb); methotrexate (Otrexup, Rasuvo); metoclopramide (Reglan); mitoxantrone; rosuvastatin (Crestor); selective serotonin reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, Symbyax, others), fluvoxamine (Luvox), paroxetine (Brisdelle, Paxil, Pexeva), and sertraline (Zoloft); sulfasalazine (Azulfidine); and topotecan (Hycamtin). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have liver disease. Your doctor will probably tell you not to take safinamide.
  • tell your doctor if you have or have ever had a mental illness such as schizophrenia (a mental illness that causes disturbed thinking, loss of interest in life, and strong or unusual emotions), bipolar disorder (mood that changes from depressed to abnormally excited), or psychosis; or if you have high or low blood pressure; dyskinesia (abnormal movements); or sleep problems. Also tell your doctor if you or a family member have or have had problems with the retina of your eyes or albinism (inherited condition that causes a lack of color in the skin, hair and eyes).
  • tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking safinamide, call your doctor.
  • tell your doctor if you are breast-feeding or plan to breastfeed.
  • you should know that safinamide may make you drowsy or may cause you to suddenly fall asleep during your regular daily activities. You might not feel drowsy or have any other warning signs before you suddenly fall asleep. Do not drive a car, operate machinery, work at heights, or participate in potentially dangerous activities at the beginning of your treatment until you know how the medication affects you. If you suddenly fall asleep while you are doing something such as watching television, talking, eating, or riding in a car, or if you become very drowsy, especially during the daytime, call your doctor. Do not drive, work in high places, or operate machinery until you talk to your doctor.
  • remember that alcohol can add to the drowsiness caused by this medication. Do not drink alcohol while you are taking safinamide.
  • you should know that some people who took medications such as safinamide developed gambling problems or other intense urges or behaviors that were compulsive or unusual for them, such as increased sexual urges or behaviors. Call your doctor if you have an urge to gamble that is difficult to control, you have intense urges, or you are unable to control your behavior. Tell your family members about this risk so that they can call the doctor even if you do not realize that your gambling or any other intense urges or unusual behaviors have become a problem.

Pregnancy

Pregnancy

There are no adequate and well-controlled studies of safinamide in pregnant women

Animal studies

  • Developmental toxicity, including teratogenic effects, was observed when safinamide was administered during pregnancy at clinically relevant doses
  • Developmental toxicity was observed at safinamide doses lower than those used clinically when safinamide was administered during pregnancy in combination with levodopa/carbidopa

Lactation

Unknown if distributed in human breast milk

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

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

What Is Safinamide?

Safinamide is monoamine oxidase inhibitor type B (MAO-B). This medicine works by allowing a chemical called dopamine (DOE pa meen) to work for longer periods of time in the brain. Low levels of dopamine in the brain are associated with Parkinson's disease.

Safinamide is given with levodopa and carbidopa to treat "wearing-off" episodes (muscle stiffness, loss of muscle control) in people with Parkinson's disease.

Safinamide may also be used for purposes not listed in this medication guide.

You should not use safinamide if you have severe liver disease.

TELL YOUR DOCTOR ABOUT ALL OTHER MEDICINES YOU USE. Some medicines can cause unwanted or dangerous effects (including death) when used within 14 days of when you take safinamide.

You should not use safinamide if you are allergic to it, or if you have:

  • severe liver disease.

Some medicines can cause unwanted or dangerous effects (including death) when used with safinamide. You should not use any of the following medicines within 14 days before or 14 days after you take safinamide:

  • amphetamines (Adderall, Dexedrine, and others);
  • cough medicine that contains dextromethorphan;
  • cyclobenzaprine;
  • methylphenidate (Concerta, Ritalin, Daytrana, and others);
  • St. John's wort;
  • another MAO inhibitor--isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others;
  • certain antidepressants such as amitriptyline (Elavil), desipramine (Norpramin), desvenlafaxine (Pristiq), duloxetine (Cymbalta), levomilnacipran (Fetzima), maprotiline (Ludiomil) , milnacipran (Savella), trimipramine (Surmontil), venlafaxine (Effexor), vilazodone (Viibryd), and many others; or
  • opioid (narcotic) medicine such as meperidine (Demerol), methadone, propoxyphene (Darvon), tramadol (Ultram, Ultracet), and others.

To make sure safinamide is safe for you, tell your doctor if you have ever had:

  • liver disease;
  • high or low blood pressure;
  • bipolar disorder, schizophrenia, or psychosis;
  • unusual urges or impulses;
  • abnormal muscle movements;
  • problems with retina of your eye; or
  • narcolepsy or other sleep disorder (or if you take medicine to help you sleep).

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether safinamide passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

What should I avoid while taking safinamide?

While taking safinamide and for 14 days after you stop, avoid eating foods that are high in tyramine, including: pickled food (such as eggs or herring), and meats that are aged, cured, smoked, or fermented.

Eating tyramine while you are taking safinamide can raise your blood pressure to dangerous levels which could cause life-threatening side effects. You should become very familiar with the list of foods to avoid while you are taking safinamide.

Some people taking this medicine have fallen asleep during normal daytime activities such as working, driving, or other physical activity. Avoid driving or operating machinery until you know how this medicine will affect you.

Safinamide dosing information

Usual Adult Dose for Parkinson's Disease:

Initial dose: 50 mg orally once a day
Maintenance dose: After 2 weeks, may increase dose to 100 mg orally once a day based on individual need and tolerability
Maximum dose: 100 mg per day

Comment:
-Higher doses have not been shown to provide additional benefit while they do increase the risk for adverse reactions.
-This drug has only been shown effective in combination with levodopa/carbidopa.

Use: As adjunctive treatment to levodopa/carbidopa in patients with PD experiencing "off" episodes.

Precautions While Using safinamide

It is very important that your doctor check your progress at regular visits to allow for changes in your dose and to check for any unwanted effects.

Do not take safinamide if you are also using amphetamine, cyclobenzaprine, dextromethorphan (eg, Pediacare®, Robitussin®), methylphenidate (Ritalin®), St. John's wort, other MAO inhibitors (MAOI) (eg, isocarboxazid, linezolid, phenelzine, selegiline, tranylcypromine, Eldepryl®, Marplan®, Nardil®, or Parnate®), narcotic pain medicines (eg, meperidine, methadone, propoxyphene, tramadol, Darvon®, Dolophine®, Ultram®), or medicine to treat depression (eg, amitriptyline, desvenlafaxine, duloxetine, milnacipran, nortriptyline, venlafaxine, Cymbalta®, Effexor® XR, Elavil®, Pamelor®, Pristiq®). Using these medicines together may cause serious unwanted effects.

Check with your doctor right away if you have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there. These may be symptoms of a serious condition called serotonin syndrome. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body.

safinamide may make you drowsy. It may even cause you to fall asleep without warning while you drive, talk, or eat. Do not drive or do anything that could be dangerous until you know how safinamide affects you.

Some people who have used safinamide had unusual changes in their behavior. Talk with your doctor if you start having problems with gambling or increased interest in sex while using safinamide.

Do not stop taking safinamide without first checking with your doctor. Your doctor may want you to reduce gradually the amount you are taking before stopping completely.

Avoid foods and drinks that are high in tyramine, because your blood pressure could get dangerously high. Your doctor should give you a complete list. In general, do not eat anything aged, fermented, or smoked, such as most cheese, most alcohol, cured meat (such as salami), pickled foods, sauerkraut, and soy sauce. Check the expiration dates on packages. Tyramine levels get higher as food gets older or if it has not been refrigerated properly.

Do not take other medicines unless they have been discussed with your doctor. This especially includes prescription or nonprescription (over-the-counter) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, since they may increase your blood pressure.

What do I need to tell my doctor BEFORE I take Safinamide?

  • If you have an allergy to safinamide or any part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have liver disease.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking safinamide within 14 days of those drugs can cause very bad high blood pressure.
  • If you are taking any of these drugs: Linezolid or methylene blue.
  • If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with this medicine, like certain drugs that are used for cough or cold, depression or other mood problems, or pain. There are many drugs that must not be taken with safinamide.
  • If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take safinamide with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Pharmacologic Category

  • Anti-Parkinson Agent, MAO Type B Inhibitor

Dosing Hepatic Impairment

Mild impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate impairment (Child-Pugh class B): Maximum dose: 50 mg once daily.

Severe impairment (Child-Pugh class C): Use is contraindicated by the manufacturer (has not been studied).

For Healthcare Professionals

Applies to safinamide: oral tablet

Cardiovascular

Common (1% to 10%): Orthostatic hypotension, hypertension
Uncommon (0.1% to 1%): Palpitations, tachycardia, sinus bradycardia, arrhythmia, hypertension, hypotension, varicose vein, QT prolongation
Rare (0.01% to 0.1%): Myocardial infarction, arterial spasm, arteriosclerosis, hypertensive crisis, cardiac murmur, abnormal cardiac stress test[Ref]

Dermatologic

Uncommon (0.1% to 1%): Hyperhidrosis, pruritus, photosensitivity reaction, erythema
Rare (0.01% to 0.1%): Furuncle, pyoderma, alopecia, blister, contact dermatitis, ecchymosis, lichenoid keratosis, night sweats, skin pain, pigmentation disorder, psoriasis, seborrhoic dermatitis[Ref]

Gastrointestinal

Common (1% to 10%): Nausea
Uncommon (0.1% to 1%): Constipation, dyspepsia, vomiting, dry mouth, diarrhea, abdominal pain, gastritis, flatulence, abdominal distension, salivary hypersecretion, gastroesophageal reflux disease, aphthous stomatitis
Rare (0.01% to 0.1%): Tooth infection, peptic ulcer, retching, upper gastrointestinal hemorrhage[Ref]

General

The most commonly reported adverse events have included insomnia, dyskinesia, somnolence, nausea, orthostatic hypotension, dizziness, and headache.[Ref]

Genitourinary

Uncommon (0.1% to 1%): Urinary tract infection, nocturia, dysuria, erectile dysfunction
Rare (0.01% to 0.1%): Micturition urgency, polyuria, pyuria, urinary hesitation, benign prostatic hyperplasia, breast disorder, breast pain[Ref]

Hematologic

Uncommon (0.1% to 1%): Anemia, leukopenia, red blood cell abnormality
Rare (0.01% to 0.1%): Eosinophilia, lymphopenia[Ref]

Hepatic

Transaminase (ALT and AST) shifts from normal to above the upper limit of normal (ULN) occurred more frequently in treated patients. During clinical trials, the percent with an ALT shift from normal to above the ULN was 5%, 7%, and 3% of patients treated with 50 mg, 100 mg, and placebo, respectively. The percent with an AST shift from normal to above the ULN was 7%, 6%, and 3% of patients treated with 50 mg, 100 mg, and placebo, respectively. No patients treated with this drug experienced an ALT increase that was 3 x ULN or higher. The incidence of patients with an increase in AST to at least 3 x ULN was similar for drug treated and placebo patients.[Ref]

Common (1% to 10%): Elevated transaminases
Uncommon (0.1% to 1%): Abnormal liver function tests
Rare (0.01% to 0.1%): Hyperbilirubinemia[Ref]

Metabolic

Uncommon (0.1% to 1%): Decreased appetite, hypertriglyceridemia, increased appetite, hypercholesterolemia, hyperglycemia, weight increased, weight loss
Rare (0.01% to 0.1%): Cachexia, hyperkalemia[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Back pain, arthralgia, muscle spasms, muscle rigidity, pain in extremity, muscular weakness, sensation of heaviness
Rare (0.01% to 0.1%): Ankylosing spondylitis, flank pain, joint swelling, musculoskeletal pain, myalgia, neck pain, osteoarthritis, synovial cyst[Ref]

Nervous system

Very common (greater than 10%): Dyskinesia (up to 21%)
Common (1% to 10%): Somnolence, dizziness, headache, Parkinson's disease
Uncommon (0.1% to 1%): Paraesthesia, balance disorder, hypoesthesia, dystonia, head discomfort, dysarthria, syncope, cognitive disorder
Rare (0.01% to 0.1%): Abnormal coordination, disturbance in attention, dysgeusia, hyporeflexia, radicular pain, Restless Legs Syndrome, sedation, gait disturbance
Frequency not reported: Neuroleptic malignant syndrome, serotonin syndrome, sleep attack/sudden onset of sleep[Ref]

During clinical trials, sleep attacks/sudden onset of sleep were reported in patients receiving 100 mg/day.

Dyskinesia was reported at 21%, 18%, and 9% during clinical trials of this drug at doses of 50 mg/day, 100 mg/day, or placebo. Dyskinesia was the most frequent cause of drug discontinuation.[Ref]

Ocular

Common (1% to 10%): Cataract
Uncommon (0.1% to 1%): Vision blurred, scotoma, diplopia, photophobia, retinal disorder, conjunctivitis, glaucoma
Rare (0.01% to 0.1%): Amblyopia, chromatopsia, diabetic retinopathy, erythropsias, eye hemorrhage, eye pain, eyelid edema, hypermetropia, keratitis, increased lacrimation, night blindness, papilledema, presbyopia, strabismus[Ref]

Oncologic

Uncommon (0.1% to 1%): Basal cell carcinoma
Rare (0.01% to 0.1%): Acrochordon, melanocytic nevus, seborrhoic keratosis, skin papilloma[Ref]

Other

Common (1% to 10%): Fall
Uncommon (0.1% to 1%): Vertigo, fatigue, asthenia, pain, feeling hot
Rare (0.01% to 0.1%): Feeling cold, decreased drug effect, drug intolerance, malaise, pyrexia, xerosis[Ref]

Psychiatric

Common (1% to 10%): Insomnia, anxiety
Uncommon (0.1% to 1%): Hallucination, depression, abnormal dreams, anxiety, confusional state, affect lability, libido increased, psychotic disorder, restlessness, sleep disorder
Rare (0.01% to 0.1%): Compulsions, delirium, disorientation, illusion, impulsive behavior, loss of libido, obsessive thoughts, paranoia, premature ejaculation, sleep attacks, social phobia, suicidal ideation, gambling[Ref]

Respiratory

Common (1% to 10%): Cough, dyspnea
Uncommon (0.1% to 1%): Rhinorrhea
Rare (0.01% to 0.1%): Bronchopneumonia, nasopharyngitis, rhinitis, bronchospasm, dysphonia, oropharyngeal pain, oropharyngeal spasm[Ref]

Hypersensitivity

A patient developed a hypersensitivity reaction consisting of swelling of tongue and gingiva, dyspnea, and skin rash. With discontinuation, the symptoms resolved but reappeared with a rechallenge a month later.[Ref]

Postmarketing report: Hypersensitivity reaction[Ref]

Some side effects of safinamide may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Dialysis

Data not available

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