Eldepryl

Eldepryl is an antiparkinsonian drug that belongs to the group of MAOI type B.

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Indications Eldepril

It is used to treat shaking palsy or symptomatic parkinsonism (as monotherapy at the initial stage of pathology development or simultaneously with levodopa drugs, and also in combination with drugs that slow down the activity of peripheral decarboxylase, or without them).

Release form

The medicine is released in tablets, in the amount of 100 pieces in 1 bottle. There is 1 such bottle in a pack.

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Pharmacodynamics

Selegiline is a selective drug from the MAO-B inhibitor category. It also has the ability to slow down the reuptake of dopamine along with its presynaptic endings. This effect enhances dopaminergic activity inside the brain.

Selegiline prolongs and enhances the action of levodopa, which allows its dosage to be reduced. When combined with levodopa medications, the drug prolongs the "on" period and shortens the "off" period, and also reduces the severity of the exhaustion phenomenon observed after the final dose.

The active ingredient does not enhance the hypertensive effect of substances such as tyramine – the so-called “tyramine effect”.

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Pharmacokinetics

Selegiline is rapidly absorbed within the gastrointestinal tract. Peak levels are observed 30-45 minutes after oral administration. The bioavailability of the element is quite low. About 10% of the unchanged substance (on average) reaches the large circle of systemic blood flow (but there is a noticeable difference in this component between different patients).

Selegiline is a lipophilic and slightly alkaline element that easily penetrates into tissues, including the brain. The distribution processes of the substance inside the body occur quickly, and the distribution volume is approximately 500 liters when taking 10 mg of the drug. After using the drug in medicinal doses, about 75-85% of its active component is synthesized with blood plasma protein.

The drug undergoes rapid metabolic processes, mainly in the liver, transforming during them into desmethylselegiline, as well as 1-methamphetamine with 1-amphetamine. These metabolic products appear in the urine and blood plasma with single and multiple administration of the drug.

The half-life of the drug is 1.5-3.5 hours. Its total clearance rate is approximately 240 l/hour. The products of drug metabolism are mainly excreted in urine, and approximately 15% is found in feces.

Due to the irreversibility of the MAO-B slowing process, the duration of the drug effect does not depend on the period of excretion of the substance, which allows the medication to be taken once a day.

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Dosing and administration

Eldepril in monotherapy is used at an early stage of pathology or in combination with levodopa drugs (along with peripheral drugs that slow down the activity of decarboxylase, or without them). The starting dose for any scheme is 5 mg - it should be taken in the morning. It is allowed to increase the daily dosage of the drug to 10 mg (it can be divided into 2 doses or the entire dose can be taken in the morning).

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Use Eldepril during pregnancy

Since there is not enough information regarding the safety of taking Eldepril during pregnancy or lactation, it is prohibited to prescribe it to these groups of patients.

Contraindications

Main contraindications:

• the presence of intolerance to selegiline or other additional elements of the drug;
• aggravated ulcer;
• combination with SSRIs and SNRIs (venlafaxine), as well as sympathomimetics, tricyclics, opioids (such as pethidine) and MAOIs (such as linezolid).

When taken simultaneously with levodopa, its contraindications must also be taken into account.

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Side effects Eldepril

Taking the medication may result in various side effects:

• Mental disorders: hallucinations and a feeling of confusion are often noted. Mood swings sometimes occur. Impulse and compulsive control may be impaired (such as hypersexuality);
• problems with the functioning of the nervous system: headaches, dyskinesia, and dizziness are often noted. Sometimes temporary sleep disorders (such as insomnia) develop. Occasionally, a feeling of excitement appears;
• cardiac dysfunction: bradycardia often appears. Sometimes a supraventricular form of tachycardia is noted. Arrhythmias occur occasionally;
• lesions affecting the vascular system: orthostatic collapse occasionally develops;
• digestive disorders: nausea is often observed. Sometimes dryness of the oral mucosa occurs;
• symptoms from the hepatobiliary system: the activity of liver enzymes often increases;
• lesions in the subcutaneous layer and skin surface: occasionally a rash occurs;
• renal and urinary disorders: urinary disorders are occasionally observed. Urinary retention is also possible.

During the use of Eldepril, negative symptoms such as tremor, vertigo, depression and psychosis may appear, as well as pain in the back, throat, chest and joints, as well as vomiting, visual disturbances, diarrhea and constipation.

Concomitant use with levodopa.

Because the drug potentiates the properties of levodopa, its negative effects (including hyperkinesia, agitation, a feeling of anxiety or confusion, arrhythmia with atypical movements, as well as dysphonia, orthostatic collapse and hallucinations) can be further enhanced by complex treatment (it is recommended to prescribe levodopa together with a drug that slows down peripheral decarboxylase).

If levodopa-associated side effects occur with this combination of drugs, its dosage should be reduced. For example, when starting to use selegiline, the dose of levodopa should be reduced by 30% on average.

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Overdose

There is no evidence of clinically significant toxicity. The effects of selegiline as a selective MAO-B inhibitor occur at doses required to treat shaking palsy (5-10 mg/day).

Signs of overdose may resemble those of non-selective MAOI intoxication. These include irritability, drowsiness, hyperactivity, restlessness, and agitation, as well as dizziness, tremors, hallucinations, severe muscle spasms, and headaches. Other symptoms include chest pain, vascular collapse, decreased or increased blood pressure, irregular or rapid pulse, respiratory depression, feverish or comatose state, respiratory failure, seizures, and hyperhidrosis. Signs of poisoning may appear within 24 hours.

The drug has no antidote. Symptomatic measures are taken.

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Interactions with other drugs

Prohibited drug combinations.

Combination with sympathomimetics may lead to a strong increase in blood pressure values.

Use with pethidine is prohibited because these drugs are known to interact and can cause death, although the mechanism of this combination has not yet been studied.

Tramadol may also interact with the drug.

Use in combination with fluoxetine leads to hyperemia, tremor, convulsions, hyperthermia, hyperhidrosis, ataxia, and a feeling of confusion or excitement. Dizziness, hallucinations, increased heart rate, decreased or increased blood pressure, comatose state and delirium may also occur. Since fluoxetine with its active metabolic products has a long half-life, there should be an interval of at least 5 weeks between stopping its use and starting treatment with Eldepryl. Selegiline with its metabolic products has a short half-life, which is why after stopping its use, fluoxetine can be started after 14 days.

Combination with tricyclics leads to the appearance of toxic symptoms from the central nervous system (development of tremor, dizziness or convulsions). Sometimes hyperhidrosis may appear or the blood pressure indicator may increase. Since the mechanism of development of such signs is poorly studied, such drugs cannot be combined.

Taking it simultaneously with MAOIs can lead to a strong and sharp decrease or increase in blood pressure.

Not recommended drug combinations.

It is necessary to combine Eldepryl with combined oral contraceptives (including ethinyl estradiol with gestagen or ethinyl estradiol with levonorgestrel) with caution, because these drugs can increase the bioavailability of the drug.

Use with food.

Selegiline is a specific MAO-B IM that differs from standard MAO IMs that inhibit both MAO-A and MAO-B elements.

The use of the drug in recommended doses after meals with a low tyramine level did not lead to the development of a hypertensive effect ("tyramine effect"). This allows taking the drug without adhering to a specific diet.

But when combining Eldepryl with standard MAOIs or MAOI-A, a strict diet is required (you need to avoid eating foods containing large amounts of tyramine - products that contain yeast, as well as mature cheese).

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Storage conditions

Eldepril should be kept out of reach of children. Temperature values are within the range of 15-25°C.

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Shelf life

Eldepryl can be used for 3 years from the date of release of the therapeutic agent.

Application for children

There is no data on the use of the drug in children, which is why it cannot be prescribed to this group of patients.

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Analogues

Analogues of the drug are Pronoran with Cyclodol, Neomidantan, Madopar and Stalevo, and in addition to Bromcriptine-kv, Parlodel, Pramipexol Orion and Azilect with Yumex. The list also includes Vinpotropil, Bromergon and Pk-merz, and in addition to Bromocriptine, Midantan and Amantadine.

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