Синемет®

General characteristics. Structure:

Active ingredients: 25 mg of a karbidopa, 250 mg of a levodopa.

Pharmacological properties:

Pharmacodynamics. The Protivoparkinsonichesky combined means - a karbidopa combination (inhibitor of a decarboxylase of aromatic amino acids) and a levodopa (the predecessor of dopamine).
Eliminates a hypokinesia, rigidity, a tremor, a dysphagy, hypersalivation.
Protivoparkinsonichesky action of a levodopa is caused by its transformation into dopamine directly in TsNS that leads to completion of deficit of 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 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, TCmax 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 dopamine which does not get through GEB, metabolites - 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 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, other - 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. Individual selection of a dose is recommended. An initial dose — on 1/2 tab. 1-2 of time a day; if necessary add 1/2 tab. every day or every other day (before obtaining optimum effect); the maximum daily dose — 8 table.

Features of use:

Carefully appoint to patients with a serious illness of cardiovascular system, lungs (including bronchial asthma), kidneys, a liver and endocrine system, a round ulcer in the anamnesis, spasms, a chronic open angle glaucoma. Periodic control of functions of a liver, the hemopoietic and cardiovascular systems, kidneys is recommended.

It is necessary to cancel gradually.

Side effects:

From CCC: 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 of a mucous membrane of an oral cavity, taste change, saliva darkening, bleeding from a GIT, an ulcer of a 12-perstny gut.
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: short wind, upper respiratory tract infections.
From integuments: 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 Hb 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 CCC - a 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.
From integuments: malignant melanoma, blood "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, asthma, indisposition, hoarseness of a voice, excitement.
Laboratory indicators: leukopenia, hypopotassemia, giperkreatininemiya and hyperuricemia, proteinuria and glucosuria.

Interaction with other medicines:

It is incompatible with MAO inhibitors.

The combination to anti-hypertensive means can exponentiate orthostatic hypotonia.

Fenotiazina, phenyl propyl ketones can reduce therapeutic effect, Phenytoinum and a papaverine — to level it.

At a high-protein diet absorption of a levodopa can be broken.

Contraindications:

Hypersensitivity, not diagnosed skin diseases, melanoma in the anamnesis, closed-angle glaucoma, pregnancy, a lactation, age (up to 18 years).

Overdose:

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

Storage conditions:

To store at a temperature not above 30 °C. To store in the place, unavailable to children. A drug Sinemetum period of validity - 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 box.