Selegiline Transdermal

Pronunciation

Pronunciation: se-LE-ji-leen
Class: Antidepressant

Trade Names

Emsam
- Transdermal system 6 mg per 24 h (20 mg per 20 cm 2 )
- Transdermal system 9 mg per 24 h (30 mg per 30 cm 2 )
- Transdermal system 12 mg per 24 h (40 mg per 40 cm 2 )

Pharmacology

Potentiation of monoamine neurotransmitter activity in the CNS resulting from inhibition of MAO activity is suspected.

Slideshow: Depression, the Risk of Suicide, and Treatment Options

Pharmacokinetics

Absorption

Following dermal application, 25% to 30% of the selegiline content is delivered systemically over 24 h. The degree of absorption may be one-third higher than amounts of 6 to 12 mg per 24 h. Because extensive first-pass metabolism occurs with oral administration, substantially higher exposure to selegiline and lower exposure to metabolites occur with transdermal dosing.

Distribution

Plasma protein binding is approximately 90%.

Metabolism

The major enzymes involved with selegiline metabolism appear to be CYP2B6, CYP2C9, and CYP3A4/5, with CYP2A6 having a minor role.

Elimination

Urine and fecal elimination account for about 10% and 2%, respectively, of a dermal dose. At least 63% of the dose is not absorbed. The mean half-lives of selegiline and its 3 metabolites ranged from 18 to 25 h.

Special Populations

Renal Function Impairment

No adjustment of dermal dose is required with renal function impairment.

Hepatic Function Impairment

No adjustment of dermal dose is required with moderate hepatic function impairment.

Gender

No differences in pharmacokinetics have been observed based on gender.

Indications and Usage

Treatment of major depressive disorder (MDD).

Contraindications

Coadministration with analgesic agents (eg, methadone, propoxyphene, tramadol), bupropion, carbamazepine, cocaine or local anesthetics, cyclobenzaprine, dextromethorphan, dual serotonin and norepinephrine reuptake inhibitors (eg, duloxetine, venlafaxine), meperidine, mirtazapine, oral selegiline or other MAOIs (eg, phenelzine), oxcarbazepine, SSRIs (eg, fluoxetine, paroxetine, sertraline), St. John's wort, sympathomimetic amines (eg, amphetamine), tricyclic antidepressants (eg, amitriptyline), or vasoconstrictors (eg, pseudoephedrine); patients with pheochromocytoma; elective surgery requiring general anesthesia; tyramine-containing foods with higher doses of selegiline; hypersensitivity to any component of the product.

Dosage and Administration

Adults

Transdermal Recommended starting and target dosage is 6 mg per 24 h. Based on clinical judgement, the dosage may be increased in increments of 3 mg per 24 h at intervals of no less than 2 wk (max, 12 mg per 24 h).

General Advice

  • Apply to dry, intact skin on upper torso (below the neck and above the waist), upper thigh, or outer surface of upper arm.
  • Apply to an area that is not hairy, oily, irritated, broken, scarred, or calloused.
  • Do not apply to area where clothing is tight, which might cause patch to rub off.
  • Gently wash area with warm water and soap, then dry thoroughly before applying patch.
  • Wash hands thoroughly with soap and water after applying patch.
  • Avoid exposing application site to external sources of direct heat, such as heating pads or electric blankets, heat lamps, saunas, hot tubs, heated water beds, and prolonged direct sunlight.
  • Remove patch after 24 h.

Storage/Stability

Store at 68° to 77°F. Do not store outside sealed pouch.

Drug Interactions

Analgesics (eg, methadone, propoxyphene, tramadol), atomoxetine, brimonidine, bupropion, carbamazepine, cocaine or local anesthetics, cyclobenzaprine, dextromethorphan, dual serotonin and norepinephrine reuptake inhibitors (eg, venlafaxine), mirtazapine, oral selegiline or other MAOIs (eg, phenelzine), oxcarbazepine, St. John's wort, SSRIs (eg, fluoxetine), sympathomimetic amines (eg, amphetamine), tricyclic antidepressants (eg, amitriptyline), vasoconstrictors (eg, pseudoephedrine)

Coadministration with selegiline is contraindicated.

Buspirone

Increased BP may occur.

Drugs affecting monoamine activity (eg, amphetamines, meperidine, pentazocine, SSRIs, tricyclic antidepressants)

Severe, life-threatening toxicity, including serotonin syndrome (eg, rigidity, muscle twitching, mental status change, autonomic instability), may occur.

General anesthetics

Patients should not undergo elective surgery requiring general anesthetics; discontinue selegiline transdermal at least 10 days prior to elective surgery.

Oral contraceptives

Selegiline plasma levels may be elevated, increasing the pharmacologic and adverse reactions.

Tyramine-containing foods, beverages, and nutritional supplements

Should be avoided.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Orthostatic hypotension (10%); low systolic BP (3%); hypertension (at least 1%).

CNS

Headache (18%); insomnia (12%); abnormal thinking, agitation, amnesia, paresthesia (at least 1%).

Dermatologic

Rash (4%); acne, pruritus, sweating (at least 1%).

EENT

Pharyngitis (3%); taste perversion, tinnitus (at least 1%).

GI

Diarrhea (9%); dry mouth (8%); dyspepsia (4%); anorexia, constipation, flatulence, gastroenteritis, vomiting (at least 1%).

Genitourinary

Dysmenorrhea, metrorrhagia, urinary frequency, UTI (at least 1%); abnormal ejaculation (1%).

Hematologic-Lymphatic

Ecchymosis (at least 1%).

Local

Application-site reaction (24%).

Metabolic-Nutritional

Weight loss (5%); weight gain (2%); peripheral edema (at least 1%).

Musculoskeletal

Myalgia, pathological fracture (at least 1%).

Respiratory

Sinusitis (3%); bronchitis, increased cough (at least 1%).

Miscellaneous

Chest pain, neck pain (at least 1%).

Precautions

Warnings

Suicidality

Compared with placebo, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for MOD and other psychiatric disorders. Appropriately monitor patients of all ages who are started on antidepressant therapy closely for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the health care provider.


Monitor

Monitor and observe patients for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of therapy or at times of increasing or decreasing the dose.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

No overall differences in efficacy have been noted between elderly and younger patients.

Concomitant illness

Use with caution in patients with disorders or conditions that can produce altered metabolism or hemodynamic responses.

Dietary modifications

Patients taking selegiline 9 mg per 24 h or 12 mg per 24 h should avoid food and beverages rich in tyramine.

Elective surgery

Ensure that patients do not undergo elective surgery requiring general anesthetics. Discontinue selegiline transdermal at least 10 days prior to elective surgery.

Hypertensive crisis

May be a risk in patients taking amine-containing medications or tyramine-containing foods if the dose of selegiline is exceeded or if plasma levels are elevated.

Hypotension

Postural hypotension, sometimes with orthostatic symptoms, can occur.

Mania/Hypomania

Activation may occur; use with caution in patients with history of mania.

Screening for bipolar disorder

Prior to initiating treatment, adequately screen patients with depressive symptoms to determine risk of bipolar disorder.

Overdosage

Symptoms

Agitation, coma, 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, seizures, severe headache, trismus, vascular collapse.

Patient Information

  • Advise patients to read the Medication Guide before starting therapy and each time the prescription is refilled.
  • Encourage patient to discuss contents of the Medication Guide with health care provider.
  • Advise patients and caregivers to be alert for the emergence of agitation, irritability, and unusual changes in behavior, as well as the emergence of suicidal thinking and behavior, and to report such symptoms immediately to the health care providers.
  • Caution patient to use the drug exactly as prescribed.
  • Instruct patient to avoid driving or other potentially hazardous activities until effect of medication is determined.
  • Instruct patients to only use 1 selegiline patch at a time.
  • Advise patients not to take oral selegiline while using the patch.
  • Caution patient to avoid exposing application site to external sources of direct heat (eg, electric blanket, heat lamps, heating pads, hot tubs, prolonged direct sunlight, saunas).
  • Advise patient that if the patch falls off, to apply a new patch at a new site and resume previous schedule.
  • Instruct patients to get up slowly from lying or sitting position and to avoid sudden position changes to prevent postural hypotension.
  • Instruct patient as to the signs and symptoms of hypertensive crisis and to seek immediate medical attention if any signs or symptoms are present.
  • Instruct patients to avoid tyramine-rich foods and beverages while on 9 mg per 24 h or 12 mg per 24 h treatment, and continue to avoid for 2 wk after a dose reduction or discontinuation.

Copyright © 2009 Wolters Kluwer Health.

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