Selegiline Hydrochloride

Selegiline hydrochloride capsules, 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. Selegiline was significantly superior to placebo on all three principal outcome measures employed: change from baseline in daily levodopa/carbidopa dose, the amount of 'off' time, and patient self-rating of treatment success. Beneficial effects were also observed on other measures of treatment success (e.g., measures of reduced end of dose akinesia, decreased tremor and sialorrhea, improved speech and dressing ability and improved overall disability as assessed by walking and comparison to previous state).

Selegiline hydrochloride capsules 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 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. 

After two to three days of selegiline treatment, an attempt may be made to reduce the dose of levodopa/carbidopa. A reduction of 10 to 30% was achieved with the typical participant in the domestic placebo controlled trials who was assigned to selegiline treatment. Further reductions of levodopa/carbidopa may be possible during continued selegiline therapy.

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.

Moreover, the importance and severity of various reactions reported often cannot be ascertained. One index of relative importance, however, is whether or not a reaction caused treatment discontinuation. In prospective pre-marketing studies, the following events led, in decreasing order of frequency, to   discontinuation of treatment with selegiline: nausea, hallucinations, confusion, depression, loss of balance, insomnia, orthostatic hypotension, increased akinetic involuntary movements, agitation, arrhythmia, bradykinesia, chorea, delusions, hypertension, new or increased angina pectoris, and syncope. Events reported only once as a cause of discontinuation are ankle edema, anxiety, burning lips/mouth, constipation, drowsiness/lethargy, dystonia, excess perspiration, increased freezing, gastrointestinal bleeding, hair l oss, increased tremor, nervousness, weakness, and weight   loss.

Experience with selegiline hydrochloride obtained in parallel, placebo controlled, randomized studies provides only a limited basis for estimates of adverse reaction rates. The following reactions that occurred with greater frequency among the 49 patients assigned to selegiline as compared to the 50 patients assigned to placebo in the only parallel, placebo controlled trial performed in patients with Parkinson's disease are shown in the following Table. None of these adverse reactions led to a discontinuation of treatment.

In all prospectively monitored clinical investigations, enrolling approximately 920 patients, the following adverse events, classified by body system, were reported.

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

Selegiline hydrochloride, USP 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 of 223.75. The molecular formula is C₁₃H₁₇N.HCI and the structural formula is as follows:

Each hard gelatin capsule with white opaque cap and white opaque body imprinted "Novitium 5 mg" on the body and "504" on the cap in red ink containing white to off-white powder. Each capsule contains 5 mg selegiline hydrochloride, USP. Inactive ingredients are citric acid anhydrous, lactose monohydrate, magnesium stearate and microcrystalline cellulose. The capsule shells contain gelatin and titanium dioxide and are imprinted with red ink. The imprinting ink contains shellac, alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, sodium hydroxide, titanium dioxide, povidone and FD&C Red #40 Aluminum Lake.