Selegiline (oral)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Pratik Bahekar, MBBS [2]
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Overview
Selegiline (oral) is a MAOI that is FDA approved for the treatment of major depressive disorder. Common adverse reactions include decreased systolic arterial pressure, orthostatic hypotension, application site reaction, weight loss, greater than of equal to 5% in body weight, diarrhea, indigestion, headache, insomnia, xerostomia.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- Major depressive disorder
- Initial, 6 mg/24 hr
- (20 mg/20 cm) patch tropically every 24 hr
- Maintenance 6 mg/24 hr patch tropically every 24 hr
- Increase at increments of 3 mg/24 hr at 2 week intervals up to 12 mg/24 hr
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Selegiline in adult patients.
Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Selegiline in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Safety is not established in children
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Selegiline in pediatric patients.
Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Selegiline in pediatric patients.
Contraindications
- Contraindicated in patients with a known hypersensitivity to this drug.
- Contraindicated for use with meperidine (DEMEROL & other trade names). This contraindication is often extended to other opioids. (See Drug Interactions.)
Warnings
Selegiline should not be used at daily doses exceeding those recommended (10 mg/day) because of the risks associated with non-selective inhibition of MAO.
The selectivity of selegiline for MAO-B may not be absolute even at the recommended daily dose of 10 mg a day. Rare cases of hypertensive reactions associated with ingestion of tyramine-containing foods have been reported in patients taking the recommended daily dose of selegiline. The selectivity is further diminished with increasing daily doses. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg a day. Severe CNS toxicity associated with hyperpyrexia and death have been reported with the combination of tricyclic antidepressants and non-selective MAOIs (Nardil, Parnate). A similar reaction has been reported for a patient on amitriptyline and selegiline. Another patient receiving protriptyline and selegiline developed tremors, agitation, and restlessness followed by unresponsiveness and death two weeks after selegiline was added. Related adverse events including hypertension, syncope, asystole, diaphoresis, seizures, changes in behavioral and mental status, and muscular rigidity have also been reported in some patients receiving selegiline and various tricyclic antidepressants. Serious, sometimes fatal, reactions with signs and symptoms that may include hyperthermia, rigidity, myoclonus, autonomic instability with rapid fluctuations of the vital signs, and mental status changes that include extreme agitation progressing to delirium and coma have been reported with patients receiving a combination of fluoxetine hydrochloride and non-selective MAOIs. Similar signs have been reported in some patients on the combination of selegiline (10 mg a day) and selective serotonin re-uptake inhibitors including fluoxetine, sertraline and paroxetine. Since the mechanisms of these reactions are not fully understood, it seems prudent, in general, to avoid this combination of selegiline and tricyclic antidepressants as well as selegiline and selective serotonin re-uptake inhibitors. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a tricyclic antidepressant or selective serotonin re-uptake inhibitors. Because of the long half-lives of fluoxetine and its active metabolite, at least five weeks (perhaps longer, especially if fluoxetine has been prescribed chronically and/or at higher doses) should elapse between discontinuation of fluoxetine and initiation of treatment with selegiline.
General precautions
Some patients given selegiline may experience an exacerbation of levodopa associated side effects, presumably due to the increased amounts of dopamine reaction with super sensitive, post-synaptic receptors. These effects may often be mitigated by reducing the dose of levodopa/carbidopa by approximately 10 to 30%. The decision to prescribe selegiline should take into consideration that the MAO system of enzymes is complex and incompletely understood and there is only a limited amount of carefully documented clinical experience with selegiline. Consequently, the full spectrum of possible responses to selegiline may not have been observed in pre-marketing evaluation of the drug. It is advisable, therefore, to observe patients closely for atypical responses.
Melanoma
Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson's disease or other factors, such as drugs used to treat Parkinson's disease, is unclear. For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using selegiline for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).
Adverse Reactions
Clinical Trials Experience
Central Nervous System
Motor/Coordination/Extrapyramidal-increased tremor, chorea, loss of balance, restlessness, blepharospasm, increased bradykinesia, facial grimace, falling down, heavy leg, muscle twitch*, myoclonic jerks*, stiff neck, tardive dyskinesia, dystonic symptoms, dyskinesia, involuntary movements, freezing, festination, increased apraxia, muscle cramps.
Mental Status/Behavioral/Psychiatric-hallucinations, dizziness, confusion, anxiety, depression, drowsiness, behavior/mood change, dreams/nightmares, tiredness, delusions, disorientation, lightheadedness, impaired memory*, increased energy*, transient high*, hollow feeling, lethargy/malaise, apathy, overstimulation, vertigo, personality change, sleep disturbance, restlessness, weakness, transient irritability.
Pain/Altered Sensation-headache, back pain, leg pain, tinnitus, migraine, supraorbital pain, throat burning, generalized ache, chills, numbness of toes/fingers, taste disturbance.
Autonomic Nervous System
dry mouth, blurred vision, sexual dysfunction.
Cardiovascular
orthostatic hypotension, hypertension, arrhythmia, palpitations, new or increased angina pectoris, hypotension, tachycardia, peripheral edema, sinus bradycardia, syncope.
Gastrointestinal
nausea/vomiting, constipation, weight loss, anorexia, poor appetite, dysphagia, diarrhea, heartburn, rectal bleeding, bruxism*, gastrointestinal bleeding (exacerbation of preexisting ulcer disease).
Genitourinary/Gynecologic/Endocrine
slow urination, transient anorgasmia*, nocturia, prostatic hypertrophy, urinary hesitancy, urinary retention, decreased penile sensation*, urinary frequency.
Skin and Appendages
increased sweating, diaphoresis, facial hair, hair loss, hematoma, rash, photosensitivity.
Miscellaneous
asthma, diplopia, shortness of breath, speech affected.
Postmarketing Experience
There is limited information regarding Selegiline (oral) Postmarketing Experience in the drug label.
Drug Interactions
- Meperidine and MAOIs.
- The occurrence of stupor, muscular rigidity, severe agitation, and elevated temperature has been reported in some patients receiving the combination of selegiline and meperidine.
- Symptoms usually resolve over days when the combination is discontinued. This is typical of the interaction of meperidine and MAOIs.
- Other serious reactions (including severe agitation, hallucinations, and death) have been reported in patients receiving this combination (see contraindications).
- Tricyclic antidepressants & selective serotonin re-uptake inhibitors
- Severe toxicity has also been reported in patients receiving the combination of tricyclic antidepressants and selegiline and selective serotonin re-uptake inhibitors and selegiline. (See warning for details.)
- Sympathomimetic medication
- One case of hypertensive crisis has been reported in a patient taking the recommended doses of selegiline and a sympathomimetic medication (ephedrine).
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): C
No teratogenic effects were observed in a study of embryo-fetal development in Sprague-Dawley rats at oral doses of 4, 12, and 36 mg/kg or 4, 12 and 35 times the human therapeutic dose on a mg/m2 basis. No teratogenic effects were observed in a study of embryo-fetal development in New Zealand White rabbits at oral doses of 5, 25, and 50 mg/kg or 10, 48, and 95 times the human therapeutic dose on a mg/m2 basis; however, in this study, the number of litters produced at the two higher doses was less than recommended for assessing teratogenic potential. In the rat study, there was a decrease in fetal body weight at the highest dose tested. In the rabbit study, increases in total resorptions and % post-implantation loss, and a decrease in the number of live fetuses per dam occurred at the highest dose tested. In a peri- and postnatal development study in Sprague-Dawley rats (oral doses of 4, 16, and 64 mg/kg or 4, 15, and 62 times the human therapeutic dose on a mg/m2 basis), an increase in the number of stillbirths and decreases in the number of pups per dam, pup survival, and pup body weight (at birth and throughout the lactation period) were observed at the two highest doses. At the highest dose tested, no pups born alive survived to Day 4 postpartum. Postnatal development at the highest dose tested in dams could not be evaluated because of the lack of surviving pups. The reproductive performance of the untreated offspring was not assessed.
There are no adequate and well-controlled studies in pregnant women. Selegiline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Selegiline (oral) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Selegiline (oral) during labor and delivery.
Nursing Mothers
It is not known whether selegiline hydrochloride is excreted in human milk. Because many drugs are excreted in human milk, consideration should be given to discontinuing the use of all but absolutely essential drug treatments in nursing women.
Pediatric Use
The effects of selegiline hydrochloride in children have not been evaluated.
Geriatic Use
There is no FDA guidance on the use of Selegiline (oral) in geriatric settings.
Gender
No information is available on the effects of gender on the pharmacokinetics of selegiline.
Race
Assessment of the carcinogenic potential of selegiline in mice and rats is ongoing. Selegiline did not induce mutations or chromosomal damage when tested in the bacterial mutation assay in Salmonella typhimurium and in an in vivo chromosomal aberration assay. While these studies provide some reassurance that selegiline is not mutagenic or clastogenic, they are not definitive because of methodological limitations. No definitive in vitro chromosomal aberration or in vitro mammalian gene mutation assays have been performed. The effect of selegiline on fertility has not been adequately assessed.
Renal Impairment
No pharmacokinetic information is available on selegiline or its metabolites in renally impaired subjects.
Hepatic Impairment
No pharmacokinetic information is available on selegiline or its metabolites in hepatically impaired subjects.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Selegiline (oral) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Selegiline (oral) in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Selegiline (oral) Administration in the drug label.
Monitoring
There is limited information regarding Selegiline (oral) Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Selegiline (oral) and IV administrations.
Overdosage
There is limited information regarding Selegiline (oral) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
Mechanism of Action
There is limited information regarding Selegiline (oral) Mechanism of Action in the drug label.
Structure
There is limited information regarding Selegiline (oral) Structure in the drug label.
Pharmacodynamics
There is limited information regarding Selegiline (oral) Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Selegiline (oral) Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Selegiline (oral) Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Selegiline (oral) Clinical Studies in the drug label.
How Supplied
There is limited information regarding Selegiline (oral) How Supplied in the drug label.
Storage
There is limited information regarding Selegiline (oral) Storage in the drug label.
Images
Drug Images
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Patient Counseling Information
Patients should be advised of the possible need to reduce levodopa dosage after the initiation of selegiline therapy. Patients (or their families if the patient is incompetent) should be advised not to exceed the daily recommended dose of 10 mg. The risk of using higher daily doses of selegiline should be explained, and a brief description of the 'cheese reaction' provided. Rare hypertensive reactions with selegiline at recommended doses associated with dietary influences have been reported. Consequently, it may be useful to inform patients (or their families) about the signs and symptoms associated with MAOI induced hypertensive reactions. In particular, patients should be urged to report, immediately, any severe headache or other atypical or unusual symptoms not previously experienced. There have been reports of patients experiencing intense urges to gamble, increased sexual urges, and other intense urges and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone, that are generally used for the treatment of Parkinson's disease, including selegiline. Although it is not proven that the medications caused these events, these urges were reported to have stopped in some cases when the dose was reduced or the medication was stopped. Prescribers should ask patients about the development of new or increased gambling urges, sexual urges or other urges while being treated with selegiline. Patients should inform their physician if they experience new or increased gambling urges, increased sexual urges or other intense urges while taking selegiline. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking selegiline.
Precautions with Alcohol
Alcohol-Selegiline interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Selegiline (oral) Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Selegiline (oral) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
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