Синемет® WEDNESDAY

General characteristics. Structure:

Active ingredients: 25 mg or 50 mg of a karbidopa, 250 mg or 500 mg of a levodopa in 1 tablet.

Pharmacological properties:

Pharmacodynamics. The Protivoparkinsonichesky combined means - a karbidopa combination (inhibitor of a decarboxylase of aromatic amino acids) and a levodopa (the predecessor of a doamin). Eliminates a hypokinesia, rigidity, a tremor, a dysphagy, hypersalivation. Protivoparkinsonichesky action of a levodopa is caused by its transformation into a dopamine directly in TsNS that leads to completion of deficit of a dopamine in TsNS. The dopamine formed in peripheral fabrics does not participate in implementation of protivoparkinsonichesky effect of a levodopa (does not get into TsNS) and ответствен for the majority of side effects of a levodopa. Karbidopa - inhibitor of a peripheral dofa-decarboxylase, reduces formation of a dopamine in peripheral fabrics that indirectly leads to increase in quantity of the levodopa coming to TsNS. Optimum combination of a levodopa and karbidopa 4:1 or 10:1.

Effect of drug is shown within the first days since the beginning of reception, sometimes - after reception of the first dose. The full effect is reached during 7 days.

Pharmacokinetics. The karbidopa given about pharmacokinetics are limited. The levodopa at intake is quickly soaked up from a GIT. Absorption - 20-30% of a dose, Tmax at oral administration - 2-3 h. Absorption depends on the speed of evacuation of contents of a stomach and on pH in it. Existence of food in a stomach slows down absorption. Some amino acids of food can compete with a levodopa for absorption from intestines and transport through GEB. In a large number contains in a small bowel, a liver and kidneys, only about 1-3% get into a brain. In not changed look it is removed by kidneys (35% during 7 h) and through intestines.

T1/2 is about 1 h, at appointment together with karbidopy - about 2 h.

It is metabolized in all fabrics, generally by decarboxylation with formation of a dopamine which does not get through GEB, metabolites - the dopamine, Norepinephrinum, Epinephrinum are removed by kidneys. About 75% are removed by kidneys in the form of metabolites during 8 h.

After oral administration by healthy faces and patients with Parkinson's disease of a karbidopa, marked radioactive isotopes, in a single dose the maximum level of radioactivity in plasma is defined by 2-4 h after reception by healthy faces and by 1.5-5 h at patients with Parkinson's disease.

Removal of drug with urine and a stake approximately equally in both groups.

Among the metabolites allocated with urine the main are альфа-метил-3-метокси-4-гидроксифенилпропионовая acid, and also альфа-метил-3,4-дигидроксифенилпропионовая acid. They make about 14 and 10% of the removed metabolites respectively. In smaller quantities 2 other metabolites are found. One of them is identified as 3,4 dihydroxyphenylacetone, another - previously as N-metilkarbidopa. The maintenance of each of these substances makes no more than 5% of total quantity of metabolites. In urine not changed karbidopa is also found. Conjugates are not revealed.

Indications to use:

Disease and Parkinson's syndrome: rigidity, bradykinesia, tremor, dysphagy, sialorrhea, orthostatic instability of a body.

Route of administration and doses:

Inside, on 1/4 таб. (250 mg / 25 mg) 2-3 times/days, then increase a dose on 1/4 таб. every 2-3 day before achievement of optimum effect. Usually optimum effect is noted on a dose 1-2 таб. (on 250 mg / 25 mg) in days.

The maximum daily dose - 1.5 g of a levodopa and 150 mg of a karbidopa (6 таб. 250 mg / 25 mg).

Features of use:

Unacceptably sudden the terminations of reception of a levodopa (at sharp cancellation development of the symptom complex reminding the malignant antipsychotic syndrome including muscular rigidity, fervescence, deviations in mentality and increase in activity of KFK in blood serum is possible).

Control of patients who needed to lower suddenly a dose of drug is necessary or to interrupt its reception, especially if the patient receives antipsychotic medicines.

Do not appoint for elimination of the extrapyramidal reactions caused by medicines.

In the course of treatment control of the mental status of the patient, a picture of peripheral blood is necessary.

Food with the high content of protein can break absorption.

Patients with glaucoma against the background of administration of drug should control intraocular pressure regularly.

It is recommended to accept during food or with a small amount of liquid, capsules are swallowed entirely.

During prolonged treatment periodic control of functions of a liver, a hemopoiesis, kidneys and cardiovascular system is reasonable.

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

After operation the usual dose can be reappointed as soon as the patient is able to accept drug orally.

Influence on ability to driving of motor transport and to control of mechanisms

During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From cardiovascular system: arrhythmia and/or heartbeat, orthostatic reactions, including decrease or increase in the ABP, a syncope; phlebitis.

From the alimentary system: vomiting, anorexia, diarrhea, a lock, dyspepsia, dryness in a mouth, taste change, saliva darkening, bleeding from a GIT, a duodenum ulcer.

From bodies of a hemopoiesis: leukopenia, thrombocytopenia, anemia, including hemolitic, agranulocytosis.

From a nervous system: dizziness, a headache, drowsiness, a malignant antipsychotic syndrome, bradykinesia episodes (a syndrome of "inclusion switching off"), a sleep disorder, including dreadful dreams, sleeplessness; psychotic reactions, including nonsense, hallucinations and paranoid thinking, confusion of consciousness, agitation, paresthesias, a depression (including with suicide intentions), dementia, increase in a libido. It was reported about development of spasms, however relationship of cause and effect is not established with administration of drug.

Allergic reactions: Quincke's disease, small tortoiseshell, skin itch, hemorrhagic vasculitis (Shenleyna-Genokh's purpura), violent rashes (including reactions similar to a pemphigus).

From respiratory system: диспноэ, upper respiratory tract infections.

Dermatological reactions: skin rash, the increased perspiration, sweat darkening, an alopecia.

From an urinary system: infections of urinary tract, frequent urination, urine darkening.

Laboratory indicators: decrease in hemoglobin and hematocrit, increase in activity of ALT, nuclear heating plant, LDG, ShchF, hyperbilirubinemia, increase in an urea nitrogen, positive test of Koombs, hyperglycemia, leukocyturia, bacteriuria and hamaturia.

Others: stethalgia, adynamy.

Other side reactions were observed at use only of a levodopa therefore can be noted at use of a combination of a levodopa and karbidopa:

From cardiovascular system: myocardial infarction.

From the alimentary system: gastrointestinal pain, dysphagy, hypersalivation, meteorism, bruxism, language burning sensation, heartburn, hiccups.

From a metabolism: hypostases, decrease or increase in body weight.

From a nervous system: ataxy, extrapyramidal frustration, falling, alarm, gait disturbance, nervousness, decrease in sharpness of thinking, decrease in memory, disorientation, euphoria, nictitating spasm, lockjaw, strengthening of a tremor, catalepsy, twitching of muscles, activation of a latent syndrome of Horner, peripheral neuropathy.

From respiratory system: throat pain, cough.

Dermatological reactions: malignant melanoma, inflows.

From sense bodys: okulogirny crisis, diplopia, vision disorder, mydriasis.

From urinogenital system: ischuria, urine incontience, priapism.

Others: abdominal pain, fatigue, weakness, lower extremity pain, диспноэ, indisposition, hoarseness of a voice, excitement.

Laboratory indicators: leukopenia, hypopotassemia, giperkreatininemiya and hyperuricemia, proteinuria and glucosuria.

Interaction with other medicines:

At simultaneous use of a levodopa with a beta adrenostimulyatorami, Dithylinum and medicines for inhalation anesthesia, increase in risk of development of disturbances of a cordial rhythm is possible; with tricyclic antidepressants - reduction of bioavailability of a levodopa; with diazepam, clozapine, Phenytoinum, a clonidine, m-holinoblokatorami, antipsychotic drugs (neuroleptics) - derivatives of phenyl propyl ketone, a difenilbutilpiperidin, thioxanthene, a fenotiazin, and also with a pyridoxine, a papaverine, Reserpinum reduction of protivoparkinsonichesky action is possible; with drugs of lithium the risk of development of diskineziya and hallucinations increases; from metildopy - aggravation of side effect.

At simultaneous use of a levodopa with MAO inhibitors (except for MAO inhibitors of V type) blood circulation disturbances are possible (reception of MAO inhibitors has to be stopped for 2 weeks). It is connected with accumulation under the influence of a levodopa of a dopamine and Norepinephrinum which inactivation is slowed down by MAO inhibitors, and high probability of development of excitement, increase in the ABP, tachycardia, face reddening and dizziness.

At the patients receiving a levodopa at use of tubocurarine the risk of the expressed decrease in the ABP increases.

Salts of iron can reduce bioavailability of a levodoa and karbidopa; the clinical importance of such interaction is unknown.

Though Metoclopramidum increases bioavailability of a levodopa, accelerating gastric emptying, nevertheless it can adversely influence control over a disease, due to its antagonism with dopamine receptors.

Contraindications:

— hypersensitivity;

— closed-angle glaucoma;

— a melanoma and suspicion on it and skin diseases of an unknown etiology;

— concomitant use of the MAO non-selective inhibitors;

— age up to 18 years.

With care: a myocardial infarction with disturbances of a rhythm (in the anamnesis), chronic heart failure and a serious illness of cardiovascular system, a serious illness of lungs (including bronchial asthma); epilepsy and convulsive attacks (in the anamnesis), GIT erosive cankers (risk of development of bleeding from upper parts of a GIT), a diabetes mellitus and dekompensirovanny endocrine diseases, a heavy liver and/or renal failure, an open angle glaucoma, pregnancy, the lactation period.

With care: pregnancy, lactation period

Overdose:

Treatment: a gastric lavage, careful observation and ECG control for early detection of arrhythmia; if necessary - antiarrhytmic therapy.

Storage conditions:

To store in the dry, protected from light place, at a temperature of 2-30 °C. To store in the place, unavailable to children. A period of validity of the drug Sinemetum of WEDNESDAY - 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister, on 10 blisters in a cardboard pack.