Эльдеприл®

General characteristics. Structure:

Active ingredient: 5,0 mg of a selegilin of a hidrokhlorid.

Excipient: Mannitolum, starch corn, cellulose microcrystallic, povidone, magnesium stearate.

Highly effective original drug of the first line for monotherapy of a disease of Parkinson and treatment in a combination with a levodopa. The molecule of a selegilin developed Orion is MAO-inhibitor of selective effect. Dopamine metabolism, the return capture oppresses him at the level of presynaptic nerves, promoting thereby increase in its concentration in kernels of extrapyramidal system. Has neuroprotective effect, it is well transferred and in case of the combined treatment with a levodopa allows to reduce the need for a levodopa on average by 30%.

Pharmacological properties:

Pharmacodynamics. Selegilin is the selection MAO-B inhibitor which also inhibits repeated capture of a dopamine and a presynaptic receptor of a dopamine. These effects exponentiate dopaminergic function in a brain.

Selegilin potentiates and prolongs effect of a levodopa that does possible a dose decline of the last. In a combination with levodopa drugs селегилин increases duration of the period of "inclusion", reduces duration of the period of "switching off" and reduces expressiveness of a phenomenon of exhaustion of a final dose. Selegilin does not exponentiate hypertensive effect of such substances as tyramine (cheese effect).

Pharmacokinetics. Selegilin is quickly absorbed from digestive tract. Peak concentration are reached in 30 minutes after oral administration. Bioavailability of substance low; on average 10% of not changed selegilin reach a big circle of blood circulation (however, there is a significant difference between different patients). Selegilin is lipophilic, slightly alkaline connection which easily gets into fabrics, including a brain. It is quickly distributed in an organism, the volume of distribution makes about 500 liters after intravenous administration of a dose of 10 mg.

At therapeutic doses of 75-85% of a selegilin contacts proteins of plasma. Selegilin is quickly metabolized, mainly, in a liver, to a desmetilselegilin, 1 Metamphetaminum and 1 amphetamine. These three metabolites were found in people in plasma and urine after reception single and repeated doses of a selegilin.

The average elimination half-life makes 1,6 hours. The general clearance of a selegilin in an organism makes about 500 liters an hour. Metabolites of a selegelin are generally removed with urine, about 15% are found in excrements. Because of irreversible inhibition of MAO-B duration of therapeutic effect does not depend on time of removal of a selegilin, and therefore reception is sufficient once a day.

Indications to use:

Parkinson's disease or symptomatic parkinsonism – as monotherapy at an early stage of a disease or in a combination with levodopa drugs.

Route of administration and doses:

Selegilin is applied as monotherapy at an early stage of a disease, or as auxiliary therapy to treatment by levodopa drugs. In both cases the initial dose makes 5 mg which accept in the morning. It is possible to increase Eldepril's dose to 10 mg a day (it is possible to accept in the morning, or to divide into two receptions). If when using drug as auxiliary therapy to treatment the side reactions caused by a levodopa arise drugs of a levodopa, the dose of the last should be lowered.

Features of use:

It is necessary to observe extra care at use of a selegilin for the patients having stomach ulcer or a duodenum, labile hypertensia, cardiac arrhythmia, heavy stenocardia, a heavy liver or renal failure, or psychosis. At the high doses (exceeding 10 mg/day), selectivity of a selegilin concerning MAO-B begins to decrease that leads to the raised MAO-A inhibition. Thus, high doses of a selegilin are connected with theoretical risk of the increased arterial pressure at patients whose diet during therapy is rich with tyramine. There are messages on temporary increase in concentration of transaminase of a liver during treatment selegiliny.

Use during pregnancy and a lactation. As the available data on safety of use of a selegilin during pregnancy and a lactation are not enough, селегилин pregnant women and the nursing women are not recommended to apply.

Influence on ability to manage motor transport and to work with mechanisms. Impact of a selegilin on ability to drive the car or mechanisms was not studied.

Side effects:

Selegilin was well had at monotherapy. As селегилин exponentiates clinical performance of a levodopa, side reactions of a levodopa can amplify. When the treatment by a levodopa which is most transferred by patients is combined with selegiliny, the patient can have involuntary movements, nausea, excitement, confusion of consciousness, a hallucination, a headache, postural hypertensia, cardiac arrhythmia and dizziness. Also it was reported about the complicated urination and rash. Therefore, with an initiation of treatment selegiliny the dose of a levodopa can be lowered on average by 30%.

Mental disorders	Extended (<1/100, <1/10)	Sleep disorders (for example sleeplessness)
Disturbances from TsNS	Extended (<1/100, <1/10)	Dryness in a mouth, the involuntary movements (for example dyskinesia), dizziness
	Single (> 1/10 000, <1/1000)	Excitement, headache
Disturbances from heart	Single (> 1/10 000, <1/1000)	Arrhythmia
Vascular disorders	Extended (<1/100, <1/10)	Postural hypertensia
Disturbances from a GIT	Extended (<1/100, <1/10)	Nausea
Gepatobiliarny disturbances	Extended (<1/100, <1/10)	Temporary increase in activity of plasma ALAT
Disturbances from skin and a hypodermic fatty tissue	Single (<1/10 000, <1/1000)	Skin rash
Disturbances from kidneys and urinary tract	Single (< 1/10 000, <1/1000)	The complicated urination

Interaction with other medicines:

During treatment selegiliny it is necessary to consider a possibility of hypertensive reaction as a result of interaction with indirect sympathomimetic drugs. It was not reported that the food containing tyramine causes hypertensive reactions during treatment selegiliny at doses which are applied to treatment of a disease of Parkinson. Use in combination with the MAO non-selective inhibitors can cause heavy hypertensia. About portability problems at use of a selegilin in combination with moklobemidy it was not reported. However simultaneous use of these drugs exponentiates hypertensive effect of tiraminopodobny substances (for example, the foodstuff containing tyramine such as the fermented food and drinks, aged cheese, smoked sausage, jerked beef, game, liver, broth, salty fish, beans and peas, sourcrout and products containing yeast). As information concerning use of a selegilin in combination with moklobemidy is limited, at the same time it is not recommended to apply these medicines.

It is necessary to avoid use of a selegilin in combination with pethidine. Tramadol can also interact with selegiliny.

It is necessary to be careful at use of a dopamine in combination with selegiliny.

Patients who at the same time received селегилин and fluoxetine have messages on side reactions. For example, the ataxy, a tremor, a hyperthermia, hyper - and hypotension, spasms, tachycardia, perspiration, reddening, dizziness and mental changes (excitement, confusion of consciousness and a hallucination) progressing up to a delirium and a coma were observed. It was reported about emergence of similar reactions at the patients receiving селегилин along with sertraline paroksetiny, venlafaksiny or fluvoksaminy. As mechanisms of these interactions are not quite clear, it is recommended to avoid a combination of a selegilin with the above-stated medicines.

As fluoxetine and its active metabolites have a long elimination half-life, between cancellation of fluoxetine and the beginning of therapy selegiliny there have to pass not less than five weeks. Selegilin and his metabolites have a short elimination half-life therefore between cancellation of a selegilin and the beginning of reception of fluoxetine of rather two-week interval.

Simultaneous use of a selegilin and tsitalopram did not cause clinical, pharmakodinamichesky or pharmacokinetic interactions. However it is necessary to be careful at simultaneous use of a selegilin with any of selective serotonin reuptake inhibitors.

It was reported about heavy symptoms from TsNS at the patients receiving a combination of tricyclic antidepressants and a selegilin. It was reported also about the separate case of death of the patient testing a hyperthermia, a tremor and excitement. Treat other side reactions which arose at the patients receiving a combination of a selegilin and tricyclic antidepressants hyper - and hypotension, dizziness, perspiration, a tremor and spasms, changes of behavior and a mental state. As mechanisms of these reactions are not quite clear, it is necessary to appoint these drugs to the patients receiving селегилин with care.

It is necessary to be careful at simultaneous use of a selegilin with the combined peroral contraceptives (gestagen/ethinylestradiol or levonorgestrel/ethinylestradiol) as they can increase bioavailability of a selegilin.

Contraindications:

Hypersensitivity to a selegilin.

Overdose:

Cases of overdose are not known. The experience got during development of a selegilin shows that influence of doses of 600 mg/day caused heavy hypotension and psychomotor excitement. Theoretically symptoms of overdose can be similar to those which are observed at use of non-selective MAO inhibitors (for example, drowsiness, dizziness, annoyance, a hyperactivity, excitement, a severe headache, hallucinations, hypertensia, hypotension, a stethalgia, the accelerated and uneven pulse, a vascular collapse, respiratory insufficiency, perspiration, heat). The specific antidote does not exist, a symptomatic treatment.

Storage conditions:

To store at the room temperature (15–25 °C), in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 100 tablets in a bottle, on 1 bottle in a cardboard box.