Сталево®

General characteristics. Structure:

Active ingredient: 50,0 mg a levodopa, 12,5 mg of a karbidop in the form of monohydrate, 200,0 mg of an endakapon.

Excipients: starch corn, Mannitolum, sodium of a kroskarmelloz, povidone, magnesium stearate.

Structure of a cover: a gipromelloza, titanium dioxide, ferrous oxide yellow, ferrous oxide red, magnesium stearate, polysorbate 80, глицерол 85%, the water purified ethanol of 96%.

The combined drug which contains three active a component. Each tablet of Stalevo contains the levodopa which is protivoparkinsonichesky means. Two other component, a karbidopa and энтакапон, improve and strengthens protivoparkinsonichesky effects of a levodopa. Stalevo is shown to the patients meeting with the repeating symptom of "dosage effect exhaustion". Clinically proved efficiency of drug of Stalevo in comparison with usual combinations of a levodopa-karbidopy allows patients to have more activity for day.

Pharmacological properties:

Pharmacodynamics. The combined protivoparkinsonichesky drug representing a levodopa combination - the metabolic predecessor of a dopamine, a karbidopa - inhibitor of a decarboxylase of aromatic amino acids and an entakapon - inhibitor catechol-au-methyltransferase (KOMT).

The levodopa increases the maintenance of a dopamine in a brain. The dopamine is formed directly of a levodopa with the participation of a decarboxylase of aromatic amino acids. The Protivoparkinsonichesky effect of a levodopa is caused by its transformation into a dopamine directly in TsNS. The levodopa is quickly decarboxylized in peripheral fabrics, turning into a dopamine which, however, through GEB does not get.

Karbidopa inhibits process of decarboxylation of a levodopa and formation of a dopamine in peripheral fabrics that indirectly leads to increase in quantity of the levodopa coming to TsNS.

As a result of dopa-decarboxylase inhibition the levodopa biotransformirutsya with participation catechol-au-methyltransferase (KOMT) in potentially dangerous metabolite of 3-O-metildopa (3-OMD).

Entakapon is reversible, the KOMT specific inhibitor, mainly peripheral action. Entakapon slows down clearance of a levodopa from a blood-groove that leads to increase in bioavailability of a levodopa, prolonging its therapeutic effect.

Pharmacokinetics. Levodopa. Absorption and distribution. Quickly, but not completely (20-30% of the accepted dose) it is soaked up from a GIT. Meal, rich with a large amount of neutral amino acids, can detain and reduce absorption.

Cmax after intake is reached in 2-3 h. Individual bioavailability makes 15-33%.

Slightly contacts proteins of a blood plasma (10-30%). Vd - 1.6 l/kg.

Metabolism and removal. Also catechol-au-methyltransferase to a dopamine, Norepinephrinum, Epinephrinum and 3-O-metildopy is actively metabolized in all fabrics by means of a dopa-decarboxylase. 75% of the accepted dose are removed with urine in the form of metabolites during 8 h. In not changed look it is removed with urine (35% for 7 h) and with a stake. The general clearance of a levodopa of 0.55-1.38 l/kg/h of T1/2 makes 0.6-1.3 h.

Karbidopa. Absorption and distribution. In comparison with a levodopa it is soaked up and absorbed slightly more slowly. Data on pharmacokinetics are limited. Contacts proteins of plasma approximately for 36%.

Individual bioavailability makes 40-70%.

Among the metabolites allocated with urine the main are: альфа-метил-3-метокси-4-гидроксифенилпропионовая acid and альфа-метил-3,4-дигидроксифенилпропионовая acid. T1/2 makes 2-3 h.

Metabolism and removal. It Biotransformirutsya in a liver to two main metabolites which are allocated with urine as glucuronides and untied structures. Not changed karbidopa is brought to 30% with urine. Among the metabolites excreted with urine the main are альфа-метил-3-метокси-4-гидроксифенилпропионовая acid and альфа-метил-3,4-дигидроксифенилпропионовая acid. T1/2 makes 0.6-1.3 h.

Entakapon. Absorption and distribution. It is quickly soaked up from a GIT. Cmax at a single dose is inside reached in 1 h. Individual bioavailability makes 35% (at a single dose in 200 mg).

Contacts proteins of a blood plasma for 98%, generally albumine; in therapeutic concentration does not force out from communication with proteins other medicines with high degree of a complex formation (including warfarin, salicylic acid, phenylbutazone, diazepam). Vd - 0.27 l/kg.

Metabolism and removal. Almost it is completely metabolized. Is exposed to effect of "the first passing" through a liver, a small amount of the entakapon which is (Е) - isomer, turns into (Z) - isomer (makes about 5% of total quantity of an entakapon in a blood plasma). The main way of metabolism of an entakapon and its active metabolite - a konjyugirovaniye with glucuronic acid.

It is brought with urine to 10-20% and with a stake and bile - for 80-90%. The general clearance makes about 0.7 l/kg/h of T1/2 makes 0.4-0.7 h.

Owing to short T1/2 at repeated appointment there is no true accumulation of a levodopa or an entakapon.

Pharmacokinetics in special clinical cases. Pharmacokinetic indicators at patients of younger (45-64 years) and more elderly (65-75 years) age are identical.

Bioavailability of a levodopa is much higher at women. Bioavailability of a karbidopa and entakapon does not depend on a sex of patients.

Metabolism of an entakapon is slowed down at patients with easy and moderate abnormal liver functions (classes A and B on a scale of Chayld-Pyyu) that leads to increase in concentration of an entakapon in a blood plasma both in an absorption phase, and in a removal phase.

The renal failure does not influence pharmacokinetics of an entakapon. Researches of pharmacokinetics of a levodopa and a karbidopa at patients with renal failures were not conducted.

Indications to use:

Parkinson's disease and syndrome of parkinsonism (except for medicinal) when use of a combination a levodopa and a karbidopa ineffectively.

Route of administration and doses:

Drug is accepted inside, irrespective of meal, without division of a tablet into parts. I define an optimum daily dose by careful individual selection. It is recommended to use one of three existing types of a dosage of drug (50/12.5/200 mg, 100/25/200 mg or 150/37.5/200 mg levodopa/karbidopa/entakapon). As a single dose it is necessary to accept only 1 таб. any dosage. The maximum daily dose - 1.5 g of a levodopa, 2 g of an entakapon, 375 mg of a karbidopa (corresponds 10 таб. Stalevo of 150/37.5/200 mg).

In need of introduction of bigger quantity of a levodopa reduce an interval between administrations of drug and/or transfer the patient to Stalevo's treatment in a bigger dosage (surely within the recommended dose).

If the smaller quantity of a levodopa is required, then increase intervals between administrations of drug and/or transfer the patient to Stalevo's treatment in a smaller dosage.

If at the same time from Stalevo other drugs containing a levodopa are used, then it is necessary to observe carefully recommendations about the general daily dose of drug.

Features of use:

Drug is contraindicated to use at pregnancy (unless the potential positive effect from administration of drug exceeds possible risk for fetation) and in the period of a lactation.

Stalevo is not intended for elimination of the extrapyramidal reactions caused by reception of medicines.

Before the planned general anesthesia drug can be accepted until oral administration is allowed the patient.

In case of long therapy of Stalevo periodic control of functions of a liver, system of a hemogenesis, kidneys, cardiovascular system is required. Control of function of cardiovascular system is required during the entire period of initial regulation of a dose of drug.

Use of drug at an open angle glaucoma is possible only at careful control of intraocular pressure.

When replacing Stalevo's by therapy a levodopa + the karbidopa (without entakapon) will be required increase in a dose of a levodopa.

Stalevo's cancellation is carried out slowly, if necessary increasing a levodopa dose.

Therapy by Stalevo's drug does not interfere with use of other protivoparkinsonichesky drugs. The daily dose of a seleginin at a concomitant use with Stalevo's drug should not exceed 10 mg.

Influence on ability to driving of motor transport and to control of mechanisms. Entakapon in combination with a levodopa causes drowsiness and incidental instant backfillings. It is necessary to refuse driving of the car and work with cars and mechanisms during administration of drug of Stalevo.

Side effects:

From TsNS and peripheral nervous system: an ataxy, numbness, a lockjaw, activation of a latent syndrome of Horner, dyskinesia (including horeimorfny, dystonic and other involuntary movements), a hyperkinesia, a bradykinesia (a phenomenon "inclusion switching off"), deterioration in symptoms of parkinsonism, a nictitating spasm, a bruxism; drowsiness, dizziness, headache, anorexia, confusion of consciousness, sleeplessness, dreadful dreams, hallucinations, excitement, concern, euphoria; changes in thinking (including paranoid thinking and psychotic episodes); a depression with development of suicide tendencies or without those; cognitive dysfunction.

From an organ of sight: diplopia, indistinct visual perception, mydriasis, okulogirny crises.

From cardiovascular system: arrhythmia, orthostatic hypotension, arterial hypertension, phlebitis.

From the alimentary system: dryness in a mouth, bitter taste in a mouth, nausea, vomiting, hypersalivation, a dysphagy, a hiccups, pains and discomfortable feelings in a stomach, a lock, diarrhea, a meteorism, a burning sensation in language, gastrointestinal bleedings, development of an ulcer of a duodenum, hepatitis.

Dermatological reactions: hyperemia of integuments, feeling of rushes of blood, hyperhidrosis, sweat discoloration (darkening), hair loss, erythematic or makulopodobny rashes, urticaria.

From an urinary system: ischuria, urine incontience, urine discoloration, priapism.

From respiratory system: stethalgias, диспноэ.

From system of a hemopoiesis: anemia (including hemolitic), thrombocytopenia, agranulocytosis.

Others: weakness, fatigue, dysphonia, malignant melanoma.

Interaction with other medicines:

The therapeutic effect of Stalevo decreases at a concomitant use with antagonists of dopamine receptors (some neuroleptics and antiemetic drugs), Phenytoinum, a papaverine.

At a concomitant use with iron preparations Stalevo's efficiency can decrease, т.к a levodopa and энтакапон form in a GIT chelate complexes with iron ions. It is necessary to observe a time interval in 2-3 h between Stalevo's receptions and ferriferous drugs.

The therapeutic effect of Stalevo can decrease at the patients receiving a high-protein diet due to the competing action of a levodopa and some amino acids.

Stalevo is compatible to an imipramine and moklobemidy, a pyridoxine a hydrochloride, diazepam, an ibuprofen.

Contraindications:

— the expressed abnormal liver functions;

— closed-angle glaucoma;

— pheochromocytoma;

— combined use with the MAO non-selective inhibitors of types A and B (for example, фенелзин, Tranylcyprominum);

— combined use with the MAO selection inhibitors of types A and B;

— a malignant antipsychotic syndrome and/or atraumatic acute рабдомиолиз (including in the anamnesis).

— children's and teenage age up to 18 years;

— pregnancy;

— period of a lactation (breastfeeding);

— hypersensitivity to drug components.

With care it is necessary to use drug at the expressed cardiovascular and pulmonary insufficiency, bronchial asthma, liver diseases, diseases of kidneys; diabetes mellitus and other dekompensirovanny endocrine diseases, GIT erosive cankers; spasms (in the anamnesis), at a myocardial infarction in the anamnesis (with the remaining disturbances of a cordial rhythm), psychosis in the anamnesis and/or in the course of treatment, a depression with suicide tendencies, asocial behavior; to an open angle glaucoma. It is necessary to be careful at simultaneous use of Stalevo with the drugs capable to cause orthostatic hypotension; with the neuroleptics blocking a dopamine (especially antagonists dopamine D2 receptors); with tricyclic antidepressants, desipramine, maprolitiny, venlafaksiny; with warfarin and drugs, metaboliziruyemy KOMT (пароксетин).

Overdose:

Symptoms: strengthening of expressiveness of side effects.

Treatment: hospitalization, gastric lavage, reception of absorbent carbon, control of functions of respiratory, cardiovascular and urinary systems, ECG monitoring; if necessary - antiarrhytmic therapy.

The pyridoxine is inefficient at Stalevo's overdose.

Storage conditions:

List B. Drug should be stored in the place, unavailable to children, at a temperature from 15 °C to 25 °C.

Issue conditions:

According to the recipe

Packaging:

30 pieces - bottles polyethylene (1) - packs cardboard.
100 pieces - bottles polyethylene (1) - packs cardboard.