Selegiline Hydrochloride

Pronunciation
( L-Deprenyl )

Pronunciation: se-LE-ji-leen HYE-droe-KLOR-ide
Class: Antiparkinson agent

Trade Names

Eldepryl
- Capsules 5 mg

Selegiline
- Tablets 5 mg

Zelapar
- Tablets, orally disintegrating 1.25 mg

Apo-Selegiline (Canada)

Pharmacology

Selective type B MAOI thought to increase dopaminergic activity. MAO enzyme breaks down catecholamines and serotonin. Selegiline may also interfere with dopamine reuptake at synapse.

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Pharmacokinetics

Absorption

C max of metabolites following a single oral dose of 10 mg are from 4 to almost 20 times more than the C max of selegiline (1 ng/mL). Bioavailability is increased 3- to 4-fold when taken with food.

Compared with the swallowed tablet, absorption is more rapid with the orally disintegrating tablet. After single doses of 1.25 and 2.5 mg orally disintegrating tablets, the mean C max is 3.34 and 4.47 ng/mL, respectively, compared with 1.12 ng/mL with the swallowed tablet.

Bioavailability is increased 3- to 4-fold when selegiline capsules are taken with food. When the orally disintegrating tablet is taken with food, the C max and AUC are about 60% of those values measured when selegiline is taken in the fasted state.

Distribution

Protein binding is up to 85%.

Metabolism

Selegiline undergoes extensive metabolism. Major metabolites are N-desmethylselegiline, L-amphetamine, and L-methamphetamine. Only N-desmethylselegiline has MAO-B–inhibiting activity. Metabolism is via CYP2B6 and CYP3A4 isozymes, and, to a minor extent, CYP2A6.

Elimination

Excretion is primarily in the urine. Following a single oral dose, the mean half-life is 2 h. The half-life increases to 10 h under steady-state conditions.

Special Populations

Renal Function Impairment

No information is available in patients with renal function impairment.

Hepatic Function Impairment

No information is available in patients with hepatic function impairment.

Elderly

Systemic exposure is about twice as high in elderly patients compared with a younger population given a single 10 mg oral dose.

Gender
Orally disintegrating tablets

There are no differences between men and women in overall AUC, T max , or elimination half-life. The C max is approximately 25% lower in men than women; this difference is not likely to be clinically important.

Race

Pharmacokinetic studies have not been conducted.

Indications and Usage

Adjunct to levodopa/carbidopa in Parkinson disease.

Contraindications

Meperidine, other opioid analgesics, certain other analgesics (dextromethorphan, methadone, propoxyphene, and tramadol); do not administer MAOIs with selegiline (at least 14 days should elapse between discontinuation of selegiline and administration of an MAOI, including other selegiline products); hypersensitivity to any component of the product.

Dosage and Administration

Tablet, capsule
Adults

PO 10 mg/day as divided dose of 5 mg each taken at breakfast and lunch. Do not exceed 10 mg/day. After 2 to 3 days of treatment, try reducing levodopa/carbidopa dose by 10% to 30%. Further reductions may be possible during continued selegiline therapy.

Orally disintegrating tablet
Adults

PO Start with 1.25 mg once a day for at least 6 wk. After 6 wk, the dosage may be increased to 2.5 mg once a day if desired benefit has not been achieved and the medication is tolerated.

General Advice

  • Take the orally disintegrating tablet in the morning before breakfast without liquid.
  • To administer the orally disintegrating tablet, peel back the backing of 1 or 2 blisters (do not push tablet through foil backing), and, using dry hands, remove tablet(s) and place on top of tongue where it will disintegrate within seconds.
  • Patient should avoid ingesting food or liquids for 5 min before or after taking the orally disintegrating tablet.
  • Each orally disintegrating tablet contains phenylalanine 1.25 mg. Patients taking the 2.5 mg dose will receive phenylalanine 2.5 mg.

Storage/Stability

Store tablets and capsules at 68° to 77°F. Dispense tablets in a tight, light-resistant container. Store orally disintegrating tablet at 59° to 86°F. Use within 3 mo of opening pouch and immediately upon opening individual blister.

Drug Interactions

Atomoxetine, brimonidine, dextromethorphan, methadone, propoxyphene, or tramadol

Increased risk of serious reactions; coadministration with selegiline is contraindicated.

Bupropion

Coadministration of bupropion and selegiline is contraindicated. Allow at least 14 days to elapse between discontinuing selegiline and starting bupropion.

CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin)

May reduce selegiline concentrations; use with caution.

Dextromethorphan

Brief episodes of psychosis or bizarre behavior may occur.

Hormonal contraceptives

Selegiline plasma concentrations may be elevated, causing a loss of selective inhibition of MAO-B and increasing the risk of selegiline adverse reactions.

Levodopa

The dopaminergic adverse reactions of levodopa may be potentiated and preexisting dyskinesia may be exacerbated.

MAOIs

Increased risk of nonselective MAO inhibition, leading to hypertensive crisis. Allow at least 14 days between discontinuation of selegiline and administration of other MAOIs, including other selegiline products. Hyperpyrexia and death have been reported with coadministration of other MAOIs (eg, phenelzine).

Meperidine

Serious, life-threatening reactions (eg, agitation, diaphoresis, fever, seizures), which may progress to apnea, coma, and death, may occur. Coadministration is contraindicated.

SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline)

Severe, life-threatening toxicity, including serotonin syndrome (eg, agitation, altered consciousness, ataxia, myoclonus, overactive reflexes, shivering), may occur. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI; at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of selegiline.

Sympathomimetics (eg, ephedrine)

Hypertensive crisis has been reported.

Tricyclic antidepressants (eg, amitriptyline)

Severe toxicity, including hyperpyrexia and death, may occur. At least 14 days should elapse between discontinuation of selegiline and starting treatment with a tricyclic antidepressant.

Tyramine-containing food

Rare, hypertensive reactions may occur even at the recommended dosage of 10 mg/day.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (3%).

CNS

Dizziness/light-headedness/fainting (14%); headache, insomnia (7%); confusion, dyskinesia (6%); hallucinations, vivid dreams (4%); ataxia, confusion, somnolence, tremor (3%); depression (2%); impulse control symptoms, increased libido, including hypersexuality; pathological gambling; seizures (postmarketing).

Dermatologic

Skin disorders (6%); rash (4%).

EENT

Rhinitis (7%); pharyngitis (4%).

GI

Nausea (11%); abdominal pain (8%); dyspepsia, stomatitis (5%); constipation, dry mouth (4%); vomiting (3%); diarrhea, dysphagia, flatulence, tooth disorder (2%).

Hematologic-Lymphatic

Ecchymosis (2%).

Metabolic-Nutritional

Hypokalemia (2%).

Musculoskeletal

Back pain (5%); leg cramps, myalgia (3%).

Respiratory

Dyspnea (3%).

Miscellaneous

Pain (8%); chest pain (2%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Capsules/Tablets

Safety and efficacy not established.

Orally disintegrating tablets

Safety and efficacy not established in children younger than 16 yr of age.

Elderly

In patients 65 yr of age and older compared with younger patients, the relative risk for treatment-related adverse reactions was at least 2-fold higher for abnormal dreams, anxiety, cheilitis, diarrhea, dizziness, dyspepsia, ECG abnormality, flu syndrome, hyperkalemia, hypertension, infection, nausea, orthostatic hypotension, pharyngitis, and somnolence.

Renal Function

Serum BUN and creatinine may be increased. Use with caution in patients with history of, or known or suspected, renal function impairment.

Hepatic Function

Use with caution in patients with a history of, or known or suspected, hepatic function impairment.

Buccal mucosa irritation

In patients who were healthy prior to therapy, the frequency of mild oropharyngeal abnormality (eg, mouth pain, swallowing pain, ulceration) was higher at the end of selegiline therapy compared with placebo.

Hallucinations

When used as an adjunct to levodopa, hallucinations have been reported.

Hyperpyrexia and confusion

Rapid dose reduction of, withdrawal of, or changes in antiparkinsonian therapy have been associated with a symptom complex resembling NMS.

Intense urges

Intense urges to gamble, increased sexual urges, or other intense urges, and the inability to control these urges have been reported in patients taking selegiline.

Maximum doses

Do not exceed recommended daily dosage of 10 mg/day (2.5 mg/day for orally disintegrating tablets) because of risks associated with nonselective inhibition of MAO (potentially serious food or drug interactions may occur at higher doses).

Melanoma

Risk of melanoma is higher in patients with Parkinson disease compared with the general population; however, it has not been determined if this is caused by the disease or the treatment.

Orthostatic hypotension

There may be an increased risk for orthostatic hypotension in the period after increasing the daily dose of selegiline.

Phenylketonurics

Selegiline orally disintegrating tablets contain phenylalanine.

Selectivity

Selegiline selectivity may not be absolute even at the recommended daily dose of 10 mg for the capsule or 2.5 mg for the orally disintegrating tablet. Rare cases of hypertensive reactions associated with tyramine-containing food have been reported in patients taking selegiline 10 mg/day.

Overdosage

Symptoms

Agitation; coma; convulsions; cool, clammy skin; death; diaphoresis; dizziness; drowsiness; faintness; hallucinations; hyperactivity; hyperpyrexia; hypertension; hypotension; irritability; opisthotonos; precordial pain; rapid and irregular pulse; respiratory depression and failure; severe headache; trismus; vascular collapse.

Patient Information

  • Encourage patient to change position slowly to prevent orthostatic hypotension.
  • Instruct patient to avoid driving or other potentially hazardous activities until effect of medication is determined.
  • Explain that dosage of levodopa/carbidopa may be reduced after initiation of adjunctive therapy.
  • Identify tyramine-containing foods; explain rationale for exclusion from diet.
  • Instruct patient to report twitching and/or eye spasms.
  • Inform patient that hallucinations may occur.
  • Inform phenylketonuric patients that selegiline orally disintegrating tablets contain phenylalanine.
  • Advise patient not to remove blister from the outer pouch until just prior to taking the orally disintegrating tablet. Peel the blister pack open with dry hands and place the tablet on the tongue, where it will disintegrate.
  • Instruct patient to avoid drinking liquids or eating food 5 min before or after taking the orally disintegrating tablet.
  • Caution patient to use drug exactly as prescribed. Explain that if drug is suddenly discontinued, parkinsonian crisis may occur.
  • Advise patient not to exceed 10 mg/day (tablets or capsules), or 2.5 mg/day (orally disintegrating tablets).
  • Inform patient and family of symptoms of hypertensive crisis. Instruct them to report severe headache or other unusual symptoms to health care provider immediately.

Copyright © 2009 Wolters Kluwer Health.

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