Overview
DESCRIPTION Selegiline hydrochloride is a levorotatory acetylenic derivative of phenethylamine. It is commonly referred to in the clinical and pharmacological literature as l-deprenyl. The chemical name is: (R)-(-)- N ,2-dimethyl- N -2-propynylphenethylamine hydrochloride. It is a white to near white crystalline powder, freely soluble in water, chloroform, and methanol, and has a molecular weight...
Mechanism of Action
CLINICAL PHARMACOLOGY The mechanisms accounting for selegiline's beneficial adjunctive action in the treatment of Parkinson's disease are not fully understood. Inhibition of monoamine oxidase, type B, activity is generally considered to be of primary importance; in addition, there is evidence that selegiline may act through other mechanisms to increase dopaminergic activity. Selegiline is best known as an irreversible inhibitor of monoamine oxidase (MAO), an intracellular enzyme associated with the outer membrane of mitochondria. Selegiline inhibits MAO by acting as a 'suicide' substrate for the enzyme; that is, it is converted by MAO to an active moiety which combines irreversibly with the active site and/or the enzyme's essential FAD cofactor.
Indications
- INDICATIONS AND USAGE Selegiline Hydrochloride Tablets USP are indicated as an adjunct in the management of Parkinsonian patients being treated with levodopa/carbidopa who exhibit deterioration in the quality of their response to this therapy. There is no evidence from controlled studies that selegiline has any beneficial effect in the absence of concurrent levodopa therapy. Evidence supporting this claim was obtained in randomized controlled clinical investigations that compared the effects of added selegiline or placebo in patients receiving levodopa/carbidopa.
Common Doses
- 10 mg
- 5 mg
Dosage
DOSAGE AND ADMINISTRATION Selegiline hydrochloride tablets USP are intended for administration to Parkinsonian patients receiving levodopa/carbidopa therapy who demonstrate a deteriorating response to this treatment. The recommended regimen for the administration of Selegiline Hydrochloride Tablets USP is 10 mg per day administered as divided doses of 5 mg each taken at breakfast and lunch. There is no evidence that additional benefit will be obtained from the administration of higher doses. Moreover, higher doses should ordinarily be avoided because of the increased risk of side effects.
Contraindications
- CONTRAINDICATIONS Selegiline hydrochloride is contraindicated in patients with a known hypersensitivity to this drug. Selegiline is contraindicated for use with meperidine. This contraindication is often extended to other opioids. (See Drug Interactions .)
Side Effects
- ADVERSE REACTIONS Introduction The number of patients who received selegiline in prospectively monitored pre-marketing studies is limited. While other sources of information about the use of selegiline are available (e.g., literature reports, foreign post-marketing reports, etc.) they do not provide the kind of information necessary to estimate the incidence of adverse events. Thus, overall incidence figures for adverse reactions associated with the use of selegiline cannot be provided. Many of the adverse reactions seen have also been reported as symptoms of dopamine excess.
Interactions
- Drug Interactions 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 ).