Eldepryl

General information

The drug is used to relieve the symptoms of Parkinson's disease by enhancing the action of dopamine in the nervous system and slowing the progression of movement disorders. It is available in convenient oral dosage forms and is often used in combination with other drugs to achieve optimal therapeutic results.

Trade name

Eldepryl

International Nonproprietary Name (INN)

Selegiline

Form of release

The drug is presented in the form of tablets for oral administration with dosages of 5 mg and 10 mg, which allows to adapt the treatment to the needs of the patient. There are also variants in the form of capsules and dissolvable tablets for sublingual administration, although tablets remain the most common form due to the ease of use and stability of dosing.

Composition

The active ingredient: selegiline hydrochloride (Selegiline hydrochloride) - 5 mg or 10 mg in one tablet. Excipients: lactose monohydrate (filler), microcrystalline cellulose (binder), magnesium stearate (lubricant), corn starch (leavening agent), povidone (stabilizer). The exact composition of excipients may vary depending on the manufacturer, which requires checking the information on the package before use.

Pharmacological properties

Pharmacodynamics

Selegiline, the active ingredient in Eldepryl, is a selective irreversible inhibitor of monoamine oxidase type B (MAO-B), an enzyme that is involved in the breakdown of dopamine in brain neurons. In Parkinson's disease, decreased dopamine levels lead to impaired motor function, including tremor, rigidity, and slowness of movement. By inhibiting the activity of MAO-B, the drug increases the concentration of dopamine in the synaptic cleft, improving the transmission of nerve impulses in dopaminergic pathways, which helps to reduce the symptoms of Parkinsonism. In addition, selegiline has neuroprotective properties, reducing oxidative stress and free radical formation that can damage neurons during disease progression.

Unlike non-selective MAO inhibitors, selegiline at recommended doses (up to 10 mg daily) has little or no effect on MAO type A, which minimizes the risk of hypertensive crises associated with tyramine metabolism from food. This makes it a safer choice for patients requiring long-term therapy. The drug may also enhance the effects of levodopa, lowering its dosage and reducing the severity of side effects such as dyskinesia. Some studies suggest that selegiline can slow the degeneration of dopaminergic neurons, although this effect remains a matter of debate and requires further study. In general, therapeutic effects are seen in improved motor activity, decreased tremor, and improved quality of life in patients in various stages of Parkinson's disease.

Pharmacokinetics

• Absorption: After oral administration, selegiline is rapidly absorbed from the gastrointestinal tract, reaching maximum plasma concentration in 30-60 minutes. Bioavailability is about 10% due to the significant effect of first passage through the liver, where the drug undergoes primary metabolism. The ingestion of food, especially rich in fat, may slow the rate of absorption, but does not affect the total absorption.
• Distribution: The volume of distribution is high (about 500 liters), indicating good penetration into tissues, including the central nervous system. Selegiline readily crosses the blood-brain barrier, providing therapeutic concentrations in the brain. Binding to plasma proteins is negligible (less than 20%), reducing the likelihood of interactions with other drugs at this level.
• Metabolism: The drug is metabolized in the liver with the participation of cytochrome P450 enzymes, mainly CYP2B6 and CYP3A4. The main metabolites - desmethylselegiline, L-amphetamine and L-methamphetamine - have weak pharmacological activity, but may contribute to the stimulant effect of the drug. Desmethylselegiline retains some ability to inhibit MAO-B, enhancing the action of the main substance
• Extraction: The elimination half-life of selegiline is about 10 hours, while its metabolites are eliminated more slowly (up to 20-24 hours). The main route of excretion is the kidneys (about 90% in the form of metabolites), the rest is excreted through the intestine with feces. In case of renal or hepatic dysfunction, excretion may be delayed, which requires correction of the regimen.

Indications for use

• Parkinson's disease in early stages as monotherapy to control symptoms and delay the need for levodopa.
• Combination therapy with levodopa in late stages of Parkinson's disease to enhance the effect and reduce fluctuations of the condition (e.g., on-off).
• Symptomatic parkinsonism due to other causes, such as postencephalitic conditions, in the absence of contraindications.

The drug is particularly useful in patients who have moderate motor impairment that requires mild correction without significant side effects.

Contraindications

• Hypersensitivity to selegiline or any of the excipients of the drug, including a history of allergic reactions.
• Simultaneous use with non-selective MAO inhibitors, serotoninergic agents (SSRIs, SSRIs and SSRIs), tricyclic antidepressants due to the risk of serotonin syndrome.
• Severe uncontrolled arterial hypertension, as the drug may increase pressure fluctuations.
• Gastric or duodenal ulcer in the acute phase because of possible mucosal irritation.
• Severe hepatic or renal dysfunction affecting metabolism and excretion.
• Pregnancy and lactation period due to lack of fetal and pediatric safety data.
• Age less than 18 years of age, as efficacy and safety in children have not been established.
• Pheochromocytoma (adrenal tumor), due to risk of acute elevation of blood pressure.

Patients with psychiatric disorders (e.g., schizophrenia) are prescribed the drug with caution because of possible worsening of symptoms.

Method of administration and dosage

How to take

Eldepryl tablets are taken orally, drinking enough water (about 100 ml). It is recommended to take them in the morning or in the morning with meals (e.g. breakfast and lunch) to avoid sleep disturbances associated with the stimulant effect of the drug. The tablets should not be chewed or crushed to ensure sustained release of the active ingredient.

Dosages for adults and children

• Adults: The initial dose is 5 mg once daily in the morning. If necessary, after 2-4 weeks, the dose is increased to 10 mg per day, divided into two doses (5 mg in the morning and 5 mg at lunchtime) or taken once in the morning. The maximum daily dose is 10 mg.
• Children: Use in persons under 18 years of age is not intended due to lack of data on safety and efficacy.

In combination with levodopa, the dosage of the latter may be reduced by 10-30% to reduce side effects.

Dose adjustment for certain conditions

Mild to moderate renal and hepatic impairment usually does not require dose adjustment, but the patient's condition should be monitored. In severe hepatic or renal dysfunction (creatinine clearance less than 20 ml/min) the drug is contraindicated. In elderly patients (over 65 years old) treatment is started with 5 mg per day taking into account possible hypersensitivity.

Side effects

• Nervous system: dizziness, insomnia, anxiety, headache, confusion, hallucinations (especially in the elderly).
• Cardiovascular system: increased blood pressure, tachycardia, rarely - arrhythmias.
• Gastrointestinal tract: nausea, dry mouth, constipation, abdominal discomfort.
• Skin reactions: rash, itching, rarely - allergic dermatitis.
• General: fatigue, tremor, muscle spasms, increased sweating.

The majority of side effects are temporary and decrease with adaptation to the drug.

Overdose

Symptoms of overdose

Exceeding the dose (more than 30 mg/day) may cause hypertensive crisis, severe agitation, convulsions, hallucinations, tachycardia, confusion, dyspnea. In severe cases, coma or cardiovascular collapse may occur.

First aid measures

Stop taking the drug and seek immediate medical attention. Until the arrival of a doctor: gastric lavage (if the drug has been taken recently), intake of activated charcoal (20-30 g). In hospital, symptomatic treatment is carried out: control of blood pressure, ECG, administration of sedatives in case of convulsions.

Interaction with other drugs

Influence on the effect of other drugs

• Combination with SSRIs (fluoxetine, sertraline), SSRIs (venlafaxine), tricyclic antidepressants is contraindicated due to the risk of serotonin syndrome.
• Exacerbates the effects of levodopa, which may require a reduction in its dose.
• Exacerbates the effects of sympathomimetics (pseudoephedrine), increasing the risk of hypertension.
• Combined use with opioids (pethidine) may cause respiratory depression or hypertensive crisis.

Compatibility with alcohol and food

In therapeutic doses (up to 10 mg/day), restrictions on foods with tyramine (cheese, wine) are minimal, but such foods should be avoided if the dose is exceeded. Alcohol increases side effects (dizziness, drowsiness) and is not recommended.

Special Instructions

Use in pregnancy and breastfeeding

The drug is contraindicated in pregnancy and lactation due to lack of data on its effect on the fetus and penetration into breast milk.

Effects on driving and mechanisms

Possible side effects (dizziness, confusion) may limit the ability to drive and operate machinery until individual reaction is evaluated.

Particularities of use in the elderly and children

• Elderly: start at 5 mg daily due to the risk of increased side effects (hallucinations, hypotension).
• Children: use before 18 years of age is not recommended.