selegiline

Selegiline is a medication used in the treatment of Parkinson’s disease, a movement disorder caused by the degeneration of nerve cells (neurons) in certain regions of the brain.

Selegiline is used as an adjunct in patients treated with levodopa/carbidopa, whose response to these medications has deteriorated. Selegiline is an antiparkinson agent that belongs to a class of medications known as monoamine oxidase type B ((MAO-B) inhibitors.

Dopamine is a chemical (neurotransmitter) in the brain that has multiple functions including the regulation of movement, learning, memory, cognition and emotion. Parkinson’s disease symptoms are primarily from damage to the neurons in the dopamine-producing region of the brain, which causes dopamine levels to drop. Selegiline prevents the breakdown of dopamine, increasing its concentration in the brain.

Selegiline works by inhibiting monoamine oxidase, an enzyme that is involved in the degradation (reuptake) of the neurotransmitters dopamine, serotonin, and norepinephrine in the central nervous system and peripheral tissues. At the doses recommended for Parkinson’s disease, selegiline selectively inhibits MAO-B, the type found in the brain which primarily breaks down dopamine. At higher doses, selegiline inhibits MAO-A also, which increases the levels of serotonin and norepinephrine as well.

• Do not use in patients with known hypersensitivity to selegiline or any of its components.
• Do not use selegiline concomitantly with the following medications:
  • Opioid drugs such as meperidine, tramadol, or methadone. It can lead to serotonin syndrome, a life-threatening reaction. At least 14 days should elapse between discontinuation of MAO inhibitors and initiation of opioids.
  • Other MAO inhibitors including linezolid, because of an increased risk for hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and any other MAO inhibitor.
  • St. John’s wort or cyclobenzaprine, a tricyclic muscle relaxant.
  • Dextromethorphan, because of reported episodes of psychosis or bizarre behavior.
  • Antidepressants including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, tetracyclic antidepressants, triazolopyridine antidepressants, because of the risk for serotonin syndrome.
• Daily doses should not exceed the recommended doses, because selegiline loses its selectivity for MAO-B at higher doses.
  • Hypertensive reactions to foods containing tyramine, an amino acid, have been reported with even recommended doses and the risk increases with higher doses, with the loss of MAO-B selectivity.
  • The precise dose at which selegiline loses its selectivity is not known and may vary with individuals.
  • There have been reports of uncontrolled hypertension with the recommended dose of selegiline taken concurrently with ephedrine, a sympathomimetic medication.
  • Monitor patients for new onset or exacerbation of hypertension.
• Selegiline can cause drowsiness and patients have reported falling asleep during activities of daily living. Caution patients and caregivers appropriately to avoid hazardous activities.
• Selegiline can cause a drop in blood pressure with postural change (orthostatic hypotension), more frequently during dose increase. The risk is higher in patients above 65 years of age.
• Selegiline may potentiate the dopaminergic effects of levodopa and lead to new onset of uncontrolled movements (dyskinesia) or exacerbate pre-existing dyskinesia. Reducing levodopa dose may lessen dyskinesia.
• Selegiline can affect the mental status and cause hallucinations, and abnormal thinking and behavior, including paranoid ideation, delusions, agitation, aggressive behavior, confusion, disorientation and psychotic-like behavior.
• Avoid using selegiline to treat patients with pre-existing psychotic disorder, it can exacerbate psychosis. In addition, certain antipsychotic drugs may decrease selegiline effects and exacerbate Parkinson’s symptoms.
• Patients on selegiline therapy may experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and an inability to control these urges. Specifically ask patients and caregivers about such urges, because patients may not recognize these urges as abnormal. Consider reducing the dose or stopping selegiline if such urges develop or worsen.
• There have been reports of neuroleptic malignant syndrome-like symptoms such as elevated temperature, muscular rigidity, altered consciousness, and autonomic instability with rapid dose reduction, withdrawal or changes in antiparkinsonian therapy.
• Selegiline can irritate the mucous membrane of the mouth and tongue and cause mouth pain, swallowing pain, swelling, redness and/or ulceration in the mouth. Treat patients appropriately.
• Selegiline contains phenylalanine, an amino acid. Use with caution in patients with phenylketonuria, an inherited disorder with inability to metabolize phenylalanine, which can lead to brain and nerve damage. The combined daily amount of phenylalanine obtained from all sources, including food and other medications, should be considered before prescribing selegiline.

Common side effects of selegiline include:

• Nausea
• Vomiting
• Oral inflammation (stomatitis)
• Swallowing difficulties (dysphagia)
• Tooth disorder
• Indigestion (dyspepsia)
• Abdominal pain
• Gas (flatulence)
• Constipation
• Diarrhea
• Dry mouth (xerostomia)
• Dizziness
• Headache
• Involuntary uncontrolled movements (dyskinesia)
• Drug-associated movement disorder (extrapyramidal symptoms)
• Tremor
• Impairment of coordination, balance and speech (ataxia)
• Drowsiness (somnolence)
• Insomnia
• Hallucination
• Psychotic-like behavior
• Depression
• Confusion
• Disorientation
• Delusion
• Mood changes
• Aggressive behavior
• Agitation
• Delirium
• Activation of mania/hypomania
• Compulsive behaviors such as uncontrolled binge eating, gambling and sexual urges
• Suicidal thoughts and behavior
• Drop in blood pressure when standing from sitting or lying down (orthostatic hypotension), particularly in geriatric patients
• Fainting (syncope)
• Leg cramps
• Muscle pain (myalgia)
• Generalized pain
• Chest pain
• High blood pressure (hypertension)
• Irregular heart rate (cardiac arrhythmia)
• Nasal inflammation (rhinitis)
• Throat inflammation (pharyngitis)
• Shortness of breath (dyspnea)
• Low blood potassium (hypokalemia)
• Urinary retention
• Skin disorders including:
  • Rash
  • Skin discoloration due to bleeding underneath (ecchymosis)
  • Skin ulcer
  • Fungal dermatitis
  • Contact dermatitis
  • Dry skin
  • Overgrowth of skin tissue (skin hypertrophy)
  • Sweating
  • Hives (urticaria)
  • Itching (pruritus)
  • Herpes simplex
• Serotonin syndrome, a serious drug reaction

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 5 mg

Capsule

• 5 mg

Tablet Disintegrating

• 1.25 mg

Adult:

Parkinson Disease

Conventional

• 5 mg orally at breakfast and 5 mg at lunch (10 mg/day)
• After 2-3 days of selegiline therapy, can begin to taper levodopa dose by 10-30% as tolerated; continue to taper based upon patient response
• Not to exceed 10 mg/day

Orally-disintegrating (with levodopa/carbidopa)

• Initial 1.25 mg orally every day, may increase after 6 weeks if inadequate response, no more than 2.5 mg/day
• Do not swallow
• Take in the morning before breakfast and without liquid; patient should avoid ingesting food or liquids for 5 minutes before and after taking medication

Renal Impairment

Tablets/capsules

• Use caution; dosage adjustment not provided in manufacturer’s labeling; not studied

Disintegrating tablets

• Mild to moderate impairment (creatinine clearance [CrCl] 30-89 mL/minute): Dose adjustment not necessary; maintenance dose determined by individual response
• Severe impairment (CrCl less than 30 ml/minute): Not recommended
• End-stage renal disease: Not recommended

Hepatic Impairment

Tablets/capsules

• Use caution; dosage adjustment not provided in manufacturer’s labeling; not studied

Disintegrating tablets

• Mild to moderate hepatic disease (Child-Pugh class A and B): Daily dose should be reduced (from 2.5 to 1.25 mg daily), depending on clinical response and tolerability
• Severe hepatic impairment (Child-Pugh class C): Not recommended

Geriatric:

Parkinson Disease

Conventional

5 mg PO at breakfast and 5 mg at lunch (10 mg/day)

Less than 5 mg/day when combined with levodopa

After 2-3 days of selegiline therapy, can begin to taper levodopa dose by 10-30% as tolerated; continue to taper based upon patient response

Not to exceed 10 mg/day

Orally-disintegrating (with levodopa/carbidopa)

Initial 1.25 mg orally every day, may increase after 6 weeks if inadequate response, no more than 2.5 mg/day

Do not take food or liquid for 5 minutes after dose

Pediatric:

Safety and efficacy not established

• Overdose of selegiline may cause restlessness (psychomotor agitation) and severe low blood pressure (hypotension).
• Selegiline overdose can inhibit both MAO-A and MAO-B, resulting in symptoms that include drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, lockjaw (trismus), backward arching of head, neck and spine (opisthotonos), convulsions, coma, rapid and irregular pulse, high blood pressure (hypertension), hypotension and vascular collapse, respiratory depression and failure, high body temperature, excessive sweating, and cool, clammy skin.
• Selegiline overdose is treated with symptomatic and supportive care. Treatments may include:
  • Induced vomiting, gastric lavage and charcoal administration to eliminate any undigested drug
  • Airway maintenance and respiratory support, if required
  • Intravenous fluids and medications based on symptoms

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Selegiline has severe interactions with at least 60 different drugs.
• Selegiline has serious interactions with at least 43 different drugs.
• Selegiline has moderate interactions with at least 109 different drugs.
• Mild interactions of selegiline include:
  • ruxolitinib
  • ruxolitinib topical

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Take selegiline exactly as prescribed.
• Report to your physician immediately if you:
  • Experience symptoms of hypertension. You may need to avoid foods containing tyramine, an amino acid.
  • Develop symptoms of drug reactions such as high fever, muscle rigidity, and/or altered consciousness.
  • Experience new onset or exacerbation of Parkinson’s symptoms.
  • Notice any changes in your usual behavior and mental status.
  • Develop new or increased urges for intense gambling, sexual or other impulsive behaviors that you are unable to control.
• Selegiline can make you drowsy and fall asleep during activities of daily living. Avoid hazardous activities such as driving and operating heavy machinery.
• Store selegiline safely out of reach of children and others.
• Seek immediate medical help or contact Poison control, in case of overdose or suspected overdose. Signs and symptoms of overdose may not appear immediately and may set in even up to 12 hours after ingestion.

• There are no adequate and well-controlled studies on the safety of selegiline use in pregnant women. Animal reproductive studies show selegiline use during pregnancy is associated with reduced fetal and newborn growth and survival.
• When treating a pregnant woman, the potential risks of taking an MAOI, particularly the risk of hypertensive crisis during pregnancy, along with the established benefits of treatment should be considered. An agent other than selegiline may be preferred in the treatment of pregnant women. 
• There are no data on the presence of selegiline or its metabolites in breast milk, the effects on milk production or the breastfed infant. Nursing mothers should avoid breastfeeding while on selegiline therapy and for 7 days following the final dose, because of the potential for serious adverse reactions in the infant, including hypertension.