Selegiline Dosage

Usual Adult Dose for Parkinson's Disease

Adjunct to levodopa/carbidopa:

Oral tablet: 5 mg twice a day at breakfast and lunch.

Oral disintegrating tablet: 1.25 mg once a day, before breakfast, for at least 6 weeks. After 6 weeks, the dose may be increased to 2.5 mg once a day if needed.

Usual Adult Dose for Depression

Major Depressive Disorder:

Initial: Apply one transdermal patch (6 mg/24 hours) to intact skin once every 24 hours.
Maintenance: 6 mg/24 hours up to a maximum of 12 mg/24 hours.

Renal Dose Adjustments

Transdermal System: No adjustments recommended for patients with mild, moderate, or severe renal impairment.

Oral: No data available for use in renally impaired patients.

Liver Dose Adjustments

Transdermal System: No adjustments are recommended in patients with mild or moderate liver impairment (Child-Pugh classification of A or B).

Oral: No data available for use in hepatically impaired patients, but caution is advised.

Dose Adjustments

Transdermal system: Dosage may be adjusted upwards in 3 mg/24 hours increments at intervals of no less than two weeks.

Oral tablet: after two to three days of treatment, an attempt may be made to reduce the dose of levodopa-carbidopa.

Precautions

Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children, adolescents, and young adults with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of selegiline transdermal system or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short term studies did not illustrate an increase in the risk of suicide with antidepressants compared to placebo in adults aged 65 or older. Depression and certain other psychiatric disorders are themselves linked with increases in the risk of suicide. Families and caregivers should be advised for the need for close observation and communication with the prescriber. Prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Selegiline transdermal system is not approved for use in pediatric patients. Furthermore, selegiline transdermal system at any dose should not be used in children under the age of 12, even when administered with dietary modifications.

Selegiline transdermal system is contraindicated for use in patients with pheochromocytoma. It should not be used concomitantly with bupropion, St. John's Wort, mirtazapine, cyclobenzaprine, oral selegiline or other monoamine oxidase (MAO) inhibitors, selective serotonin reuptake inhibitors, dual serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, centrally acting analgesic agents, sympathomimetic amines, cold products, and weight-reducing preparations that contain vasoconstrictors. Carbamazepine and oxcarbazepine are contraindicated in patients administered selegiline. The oral formulation is contraindicated for use with meperidine or other oral opioids.

The manufacturer suggests that dietary restrictions are generally unnecessary when oral selegiline is taken at normal therapeutic doses (10 mg per day). However, at higher doses (or perhaps in some small or particularly sensitive individuals), dietary restriction of foods containing large amounts of tyramine may be indicated.

Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of nine antidepressant drugs (SSRIs and others) in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking of behavior (suicidality) during the first few months of treatment in those receiving antidepressants. No suicides occurred in these trials.

The pooled analysis of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 subjects. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in patients with MDD. The risk differences (drug vs. placebo), however, were relatively similar with age strata and across indications. There were suicides in the adult trials, but the number was not adequate to reach any conclusion about drug effect on suicide.

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of therapy, or at times of dose changes, either increases or decreases.

The following side effects, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such side effects and either the worsening of depression and/or the emergence of suicidal impulses has not been determined, there is concern that such symptoms may represent precursors to emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possible discontinuing the drug, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

Families and caregivers being treated with antidepressants for MDD or other indications, both psychiatric and nonpsychiatric, should be made aware about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observations by caregivers and families. Prescriptions for selegiline transdermal system should be written for the smallest amount of patches consistent with good patient management, in order to reduce the risk of overdose.

A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is not known. However, prior to initiating therapy with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, depression, and bipolar disorder. It should be noted that selegiline transdermal system is not approved for treating bipolar depression.

MAO inhibitors have been associated with hypertensive crises caused by the ingestion of foods containing high amounts of tyramine. Tyramine rich foods and beverages should be avoided beginning on the first day of therapy with the transdermal system of selegiline 9 mg/24 hours or 12 mg/24 hours, and should continue to be avoided for two weeks after a dose reduction to 6 mg/24 hours or following the discontinuation of the 9 mg/24 hours or 12 mg/24 hours treatment. Patients receiving the higher doses should follow the recommended "Dietary Modifications Required for Patients Taking Selegiline Transdermal System 9 mg/24 hours and 12 mg/24 hours." If a hypertensive crisis occurs, the drug should be discontinued immediately and therapy to lower blood pressure should be instituted.

The selectivity of oral selegiline for MAO B decreases as doses are increased. At higher doses, inhibition of MAO A may occur. Inhibition of MAO A may predispose patients to hypertensive crises after ingestion of vasoactive amines.

Serious, sometimes fatal, central nervous system (CNS) toxicity referred to as the "serotonin syndrome" has been reported with the combination of nonselective MAOIs with certain other drugs (tricyclic or SSRI antidepressants, amphetamines, meperidine, or pentazocine). Serotonin syndrome is characterized by 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. Similar, less severe, syndromes have been reported in a few patients receiving oral selegiline and one of the mentioned drugs. All drug therapies surrounding the initiation of discontinuation of selegiline should be evaluated closely for potential drug interactions. A minimum time period equal to 4 to 5 half-lives of the drug or active metabolite should elapse before starting or stopping selegiline when using a drug that is contraindicated with selegiline.

As with other MAOIs, postural hypotension, sometimes with orthostatic symptoms, can occur with selegiline transdermal system. It is recommended that dose increases in the elderly should be made with caution and patients should be closely monitored for postural changes in blood pressure throughout treatment. Dose increases should be made cautiously in patients with pre-existing orthostasis. Postural hypotension may be relieved by having the patient recline until the symptoms have subsided. Patients should be cautioned to change positions slowly. Patients displaying orthostatic symptoms should have appropriate dosage adjustments as necessary.

Selegiline should be used with caution in patients with cardiovascular disease because it can cause tachycardia, hypertension, hypotension, and arrhythmias and aggravate angina pectoris. Selegiline transdermal system has not been systematically evaluated in patients with unstable heart disease or a history of myocardial infarction. Such patients were generally excluded from clinical trials during the product's premarketing testing.

Clinical experience with selegiline transdermal system in patients with certain concomitant systemic illnesses is incomplete. Caution is recommended when using selegiline transdermal system in patients with disorders or conditions that can produce altered metabolism or hemodynamic responses.

Because of the risks associated with nonselective inhibitors of MAO, the maximum recommended daily doses should not be exceeded.

Selegiline may potentiate the dopaminergic side effects of levodopa and may cause or exacerbate preexisting dyskinesia. Levodopa dosage reduction may ameliorate this side effect.

Hallucinations were reported as an adverse event in twice as many patients treated with selegiline as treated with placebo. Patients should be instructed to report promptly to their health care provider any hallucinations should they develop.

The orally disintegrating tablet contains phenylalanine.

Selegiline should be discontinued at least 10 days prior to elective surgery requiring general anesthesia. If surgery is necessary sooner, benzodiazepines, mivacurium, rapacuronium, fentanyl, morphine, and cocaine may be used with caution.

Selegiline should be used with caution in patients with glaucoma or urinary retention as it may exacerbate these conditions.

Patients diagnosed with Parkinson's disease using selegiline should undergo periodic dermatologic screening for melanoma. Some epidemiologic studies have shown that patients with Parkinson's disease have a higher risk (2- to 4-fold higher) of developing melanoma than the general population, although the exact cause has not been identified.

An increased frequency of mild oropharyngeal abnormalities have been observed with the use of the orally disintegrating tablet. Periodic examination of the tongue and oral mucosa should be performed.

Dialysis

Data not available

Other Comments

Patients should avoid ingesting food or liquids for 5 minutes before and after taking selegiline orally disintegrating tablets.

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