Eselex

Uses

Eselex is used for 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. Eselex 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 selfrating 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).

Eselex is also used to associated treatment for these conditions: Attention Deficit Hyperactivity Disorder (ADHD), Major Depressive Disorder (MDD), Parkinson's Disease (PD)

How Eselex works

Although the mechanisms for selegiline's beneficial action in the treatment of Parkinson's disease are not fully understood, the selective, irreversible inhibition of monoamine oxidase type B (MAO-B) is thought to be of primary importance. MAO-B is involved in the oxidative deamination of dopamine in the brain. Eselex binds to MAO-B within the nigrostriatal pathways in the central nervous system, thus blocking microsomal metabolism of dopamine and enhancing the dopaminergic activity in the substantial nigra. Eselex may also increase dopaminergic activity through mechanisms other than inhibition of MAO-B. At higher doses, selegiline can also inhibit monozmine oxidase type A (MAO-A), allowing it to be used for the treatment of depression.

Dosage

Eselex dosage

Eselex Hydrochloride is 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 Eselex 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

Toxicity

LD₅₀=63 mg/kg (rats, IV)

Precaution

Some patients given selegiline may experience an exacerbation of levodopa associated side effects, presumably due to the increased amounts of dopamine reaction with super sensitive, post-synaptic receptors. These effects may often be mitigated by reducing the dose of levodopa/carbidopa by approximately 10 to 30%.

The decision to prescribe selegiline should take into consideration that the MAO system of enzymes is complex and incompletely understood and there is only a limited amount of carefully documented clinical experience with selegiline. Consequently, the full spectrum of possible responses to selegiline may not have been observed in pre-marketing evaluation of the drug. It is advisable, therefore, to observe patients closely for atypical responses.

Food Interaction

• Avoid tyramine-containing foods and supplements. Consuming foods containing tyramine such as yogurt, aged cheese, ripe bananas, wine, and sourdough bread may increase the risk of having an uncontrolled hypertensive reaction.
• Take before a meal. Take selegiline oral disintegrating tablets before breakfast and at least 5 minutes before or after any food or drink. Taking selegiline with food reduces the AUC by approximately 60%.
• Take with food. Take selegiline capsules or tablets with breakfast and lunch. Food can increase the exposure to selegiline by 3-4 fold.

[Major] GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase inhibitors (MAOIs).

The mechanism is inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact.

Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules.

Although selegiline is considered a selective inhibitor of MAO-B, the selectivity may not be absolute even at recommended dosages.

Rare cases of hypertensive reactions associated with ingestion of tyramine-containing foods have been reported in patients taking the recommended daily oral dose of selegiline.

Data for transdermal selegiline indicate that the 6 mg<24 hour dosage may be given safely without dietary restrictions.

However, limited data are available for higher dosages.

MANAGEMENT: Patients treated with oral selegiline and transdermal selegiline (greater than 6 mg<24 hour) should preferably avoid consumption of products that contain large amounts of amines and protein foods in which aging or breakdown of protein is used to increase flavor.

These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, salamis, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, sauerkraut, yogurt, papaya products, meat tenderizers, fava bean pods, protein extracts, yeast extracts, and dietary supplements.

Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well.

At least 14 days should elapse following discontinuation of selegiline therapy before these foods may be consumed.

Specially designed reference materials and dietary consultation are recommended so that an appropriate and safe diet can be planned.

Patients should also be advised to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, difficulty thinking, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms.

The recommended dosages of selegiline should not be exceeded, as it can increase the risk of nonselective MAO inhibition and a hypertensive crisis.

Eselex Alcohol interaction

[Moderate] GENERALLY AVOID:

Alcohol may potentiate some of the pharmacologic effects of central nervous system (CNS)-active agents.

Use in combination may result in additive CNS depression and/or impairment of judgment, thinking, and psychomotor skills.

Patients receiving CNS-active agents should be advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled against driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Eselex Hypertension interaction

[Moderate] Eselex can cause hypertensive reactions and it should be used with caution in patients with hypertension.

Patients should report any symptoms such as occipital headache, palpitations, neck stiffness or soreness, nausea, sweating, dilated pupils and photophobia.

Patients receiving therapy need to have monitored their blood pressure frequently to detect any evidence of pressor response.

Additionally, patients should be advised to avoid foods and drinks with high tyramine content such as cheese, sour cream, beer, liver, bananas and others, as these might trigger a hypertensive crisis.

Eselex Drug Interaction

Major: amphetamine / dextroamphetamine, duloxetine, escitalopramModerate: diphenhydramine, clonazepam, pregabalin, pramipexole, carbidopa / levodopa, quetiapine, carbidopa / levodopa, carbidopa / levodopa, alprazolamUnknown: aspirin, ubiquinone, omega-3 polyunsaturated fatty acids, atorvastatin, levothyroxine, cyanocobalamin, ascorbic acid, cholecalciferol

Eselex Disease Interaction

Major: hypotension, major psychotic disorders, severe renal dysfunctionModerate: hypotension, cardiac disease, glaucoma, hypertension, liver disease, melanoma, sleep disorders, urinary retention

Elimination Route

Rapidly absorbed from the gastrointestinal tract.

Half Life

1.2-2 hours

Pregnancy & Breastfeeding use

Pregnancy Category C. No teratogenic effects were observed in a study of embryo-fetal development in Sprague-Dawley rats at oral doses of 4, 12, and 36 mg/kg or 4, 12 and 35 times the human therapeutic dose on a mg/m2 basis.

Nursing Mothers: It is not known whether selegiline hydrochloride is excreted in human milk. Because many drugs are excreted in human milk, consideration should be given to discontinuing the use of all but absolutely essential drug treatments in nursing women.

Contraindication

Eselex is contraindicated in patients with a known hypersensitivity to this drug. Eselex is contraindicated for use with meperidine. This contraindication is often extended to other opioids.

Special Warning

Renal Impairment: No pharmacokinetic information is available on selegiline or its metabolites in renally impaired subjects.

Hepatic Impairment: No pharmacokinetic information is available on selegiline or its metabolites in hepatically impaired subjects.

Pediatric Use: The effects of selegiline hydrochloride in children have not been evaluated.

Innovators Monograph

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