Eldepril

Eldepril is an antiparkinsonian medicine that belongs to the MAO group of type B.

[1], [2]

Indications of the eldepril

It is used to treat trembling paralysis or the symptomatic form of parkinsonism (as a monotherapy at the initial stage of pathology development or concomitantly with levodopa medicines, and also in combination with drugs that slow down peripheral-type decarboxylase activity, or without them).

Release form

Release of the medication occurs in tablets, in an amount of 100 pieces inside the 1st vial. In a pack - 1 such a bottle.

[3]

Pharmacodynamics

Selegiline is an elective drug from the IMAO-B category. It also has the ability to slow down the processes of re-uptake of dopamine along with its presynaptic endings. This effect increases dopaminergic activity within the brain.

Selegiline prolongs and intensifies the action of levodopa, so that its dosage can be reduced. When combined with levodopa medicines, the drug prolongs the "on" period, as well as shortens the "off" period, and in addition reduces the manifestation of the phenomenon of exhaustion observed after the final dose.

The active element does not increase the hypertensive effects of substances such as tyramine, the so-called "tyramine effect."

[4], [5], [6], [7]

Pharmacokinetics

Selegiline undergoes rapid absorption in the gastrointestinal tract. Peak values are noted after a lapse of 30-45 minutes after oral administration. The level of bioavailability of the element is rather low. About 10% of unchanged substance (on average) reaches a large range of systemic blood flow (but between different patients there is a perceptible difference in this component).

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

The drug quickly passes the metabolic processes, mainly inside the liver, converting during them into desmethylselegiline, and in addition 1-methamphetamine with 1-amphetamine. These metabolic products appear inside the urine and blood plasma for a one-time and multiple-dose medication.

The half-life of drugs is 1.5-3.5 hours. The indicator of its total clearance is approximately 240 liters / hour. The metabolic products of the drug are mainly excreted in the urine, and about 15% are found in feces.

Due to the irreversibility of the MAO-B deceleration process, the duration of the drug exposure does not depend on the excretion period of the substance, which allows taking the medication once per day.

[8], [9]

Dosing and administration

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

[12]

Use of the eldepril during pregnancy

Because there is not enough information regarding the safety of taking Eldepril during pregnancy or lactation, it is forbidden to assign it to these groups of patients.

Contraindications

The main contraindications:

• the presence of intolerance in relation to selegiline or other additional elements of drugs;
• exacerbated ulcer;
• combination with SSRI and IPIs (venlafaxine), as well as sympathomimetics, tricyclics, opioids (such as pethidine) and MAOI (such as linezolid).

When taking concomitantly with levodopa, it is also necessary to take into account its contraindications.

[10]

Side effects of the eldepril

Taking medication can lead to the appearance of various side symptoms:

• mental disorders: often hallucinate and sensation of confusion. Sometimes there are changes in mood. Possible violation of control in the field of impulses and compulsions (such as hypersexuality);
• problems in the work of the National Assembly: often mark headaches, dyskinesia, as well as dizziness. Sometimes develop temporary sleep disorders (such as insomnia). Occasionally a feeling of excitement appears;
• violations of cardiac function: often there is a bradycardia. Sometimes the supraventricular form of tachycardia is noted. Occasionally, arrhythmias occur;
• lesions affecting the vascular system: orthostatic collapse occasionally develops;
• digestive function disorders: often there is nausea. Sometimes there is dryness of the oral mucosa;
• symptoms from the hepatobiliary system: the activity of the action of liver enzymes is often increased;
• lesions in the subcutaneous layer and skin surface: occasionally there is a rash;
• renal impairment and problems with the urinary function: occasionally there is an upset urination. There may also be a delay in urination.

During the use of Eldepril, such negative symptoms as tremor, vertigo, depression and psychosis may appear, and in addition pains in the back, throat, sternum and joints, as well as vomiting, visual disorders, diarrhea and constipation.

Simultaneous use with levodopa.

Because the drug potentiates the properties of levodopa, its negative manifestations (including hyperkinesia, agitation, sensation of anxiety or confusion, arrhythmia with atypical movements, and in addition dysphonia, orthostatic collapse and hallucinations) can be further intensified in complex treatment (it is recommended to prescribe levodopa together with a drug that slows peripheral decarboxylase).

When associated with levodopa side effects associated with such a combination of drugs, it is necessary to reduce its dosage. For example, when you start using selegiline, the size of the portion of levodopa should be reduced by 30% on average.

[11]

Overdose

There is no information about clinically significant intoxication. The effect of selegilin in the form of selective MAOI-B develops using the portions required for the treatment of a tremor paralysis (5-10 mg / day).

Signs of an overdose may be like manifestations of intoxication with indiscriminate MAOIs. Among such feelings of irritability, drowsiness, hyperactivity, anxiety and excitement, and in addition dizziness, tremors, hallucinations, severe muscle spasms and headaches. This list also includes pain in the sternum, a collapse affecting the vascular system, a decrease or increase in blood pressure, irregularity and acceleration of the pulse, respiratory depression, febrile or coma, respiratory insufficiency, convulsions and hyperhidrosis. Symptoms of poisoning can occur within 24 hours.

The medicine does not have an antidote. Symptomatic measures are carried out.

[13], [14], [15]

Interactions with other drugs

Prohibited medicinal combinations.

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

The use with pethidine is prohibited, because it is known that these drugs may lead to death during the interaction, although the mechanism of this combination has not yet been studied.

Tramadol can also enter into a drug interaction with the drug.

Application in combination with fluoxetine leads to the appearance of hyperemia, tremor, seizures, hyperthermia, hyperhidrosis, ataxia, and besides sensation of confusion or arousal. Also, dizziness, hallucinations, a rapid heartbeat, a decrease or increase in blood pressure, coma and delirium may occur. Because fluoxetine with its active metabolic products has a long half-life, between the cessation of its use and the beginning of treatment with Eldepril, there should be an interval of at least 5 weeks. With seleghiline and its metabolism products, a short half-life, which is why after the cancellation of its intake, the use of fluoxetine can be started after 14 days.

Combination with tricyclics leads to the appearance of toxic symptoms from the side of the central nervous system (development of tremors, dizziness or convulsions). Sometimes there may be hyperhidrosis or an increase in blood pressure. Because the mechanism of development of such features is poorly understood, it is impossible to combine such drugs.

Admission simultaneously with MAOI can lead to a strong and dramatic decrease or increase in pressure.

Not recommended combinations of drugs.

It is necessary to combine with caution Eldepril with oral contraceptives of a combined nature (among them ethinyl estradiol with gestagen or ethinyl estradiol with levonorgestrel), because these drugs are able to increase the bioavailability of the drug.

Eating with food.

Selegilin is a specific MAOI-B, which differs from standard MAOIs that have a depressing effect on the elements MAO-A and MAO-B.

The use of drugs in recommended portions after ingestion of food with a low level of tyramine did not lead to the development of a hypertensive effect (the "tyramine effect"). This allows you to take the drug without adhering to a specific diet.

But with the combination of Eldepril with standard MAOIs or IMAO-A, a strict diet is necessary (it is necessary to abandon the intake of food containing large quantities of tyramine - products containing yeast as well as mature cheese).

[16], [17]

Storage conditions

Eldepril is required to be kept out of the reach of children. Temperature values are within the limits of 15-25 ° C.

[18]

Shelf life

Eldepril can be used for 3 years after the release of the therapeutic agent.

Application for children

There is no data on the use of drugs for children, because of what it can not be assigned to this group of patients.

[19],

Analogues

Analogues of the drug are medicines Pronoran with Cyclodolum, Neomidantanum, Madopar and Stalevo, and in addition Bromkriptin-kv, Parlodel, Pramipexol Orion and Azilect with Yumeks. The list also includes Vinpotropil, Bromergon and Pk-Merz, and besides Bromocriptine, Midantan and Amantadine.

[20], [21], [22]