Expiration date: 08/2025

Release form, composition and packaging

Tablets light pink color with inclusions, ploskotsylindriceskie, with facet and two intersecting risks on one side and engraved "Syndopa" on the other.

1 tablet contains:

levodopa 250 mg

carbidopa 25 mg

Excipients: corn starch, cellulose microcrystalline, lactose, colouring agent Ponceau 4R lake, povidone K30, butylhydroxyanisole, talc purified, magnesium stearate, silica colloidal anhydrous, sodium starch of glycolate, corn starch dried.

10 PCs. - strips of aluminium foil (5) - packs of cardboard.

Pharmacological action

The structure of levodopa is an amino acid formed from L-tyrosine. Dopamine is formed directly from levodopa in the cytoplasmic part of the enzyme decarboxylase of aromatic L-amino acids. The end result of the effect of dopamine is inhibition of neuronal activity in the striatum of the brain. Quickly decarboxylases levodopa in peripheral tissues under the influence of the dependent operatorsin decarboxylase of aromatic amino acids, turning into dopamine, which, however, through the blood-brain barrier is not penetrated.

Carbidopa inhibits the process of decarboxylation of levodopa in peripheral tissues, it does not penetrate the blood-brain barrier and does not affect the conversion of levodopa into dopamine in the CNS. Thus, the combination of carbidopa and levodopa can increase the amount of levodopa entering the brain. The joint intake doubles the bioavailability of carbidopa levodopa. The introduction of carbidopa never leads to complete inhibition of dofadekarboksilazy.

Pharmacokinetics

Levodopa

Suction

Levodopa is absorbed by active transport from the gastrointestinal tract, the passage through the blood-brain barrier is also carried out through active mechanisms. Barrier to the absorption of levodopa is the availability of dofadekarboksilazy in the intestinal wall. From the stomach levodopa is absorbed in limited quantities. The rate of gastric emptying plays a key role in the absorption of the drug. Factors that slow gastric emptying (food, m-holinoblokiruta funds) are delaying the passage of the drug into the duodenum and slow its absorption. The C max of the drug in blood is reached in 1-2 hours after administration.

Distribution

The volume of distribution for levodopa is 0.9-1.6 l/kg. While maintaining the activity dofadekarboksilazy total clearance of levodopa in plasma is 0.5 l/kg/h. l-DOPA crosses the blood-brain barrier by facilitated diffusion. The endothelium of capillaries of the brain also contains dofadekarboksilazy as a second potential barrier to receipt of levodopa in the brain, however, these capillaries decarboxylases a minor part of the administered dose of levodopa.

Metabolism

Approximately 70-75% of internally administered levodopa is metabolized in the intestinal wall (effect of "first pass"). The liver's first pass metabolism participation hasn't. With increasing doses of levodopa, the number of drug, subjected to decarboxylation in the intestine, decreases. Levodopa is not associated with blood plasma proteins. Decarboxylation of levodopa DOPA-decarboxylase is the main way of formation of dopamine from levodopa. A large number of this enzyme located in the intestine, liver and kidneys. Methoxylamine levodopa is influenced by the catechol-O-methyltransferase with the formation of Z-O-metildofy is the second way of metabolism of levodopa. Prolonged treatment of this metabolite can accumulate. Transamination is an additional way of the metabolism of levodopa. The end product of this way is waniliowe, vinilacetat and 2,4,5-trihydroxytoluene acid. All metabolic pathways, with the exception of transamination are irreversible.

Selection

In combination with carbidopa, T1/2 of levodopa is increased to 3 h and up To 69% of levodopa can be detected in the urine of humans in the form of dopamine and its metabolites - vinylimidazole acid, norepinephrine, homovanillic acid, dehydrophenylalanine acid.

Carbidopa

In recommended doses carbidopa does not penetrate the blood-brain barrier. C max in plasma achieved through 2-4 h. Approximately 50% of carbidopa is excreted in the urine and feces. 35% of carbidopa that are excreted by the kidneys, excreted unchanged.

Dosage

Inside, a small amount of food or after meals with water and without chewing. Since there is a competition between aromatic amino acids and levodopa in the suction, during use of the drug should avoid consuming large amounts of proteins. The average daily dose of carbidopa needed to suppress the peripheral conversion of levodopa is 70-100 mg. Excess of 200 mg of carbidopa does not entail further enhance the therapeutic effect. The daily dose of levodopa should not exceed 2000 mg.

Initial dose of 1/2 a tablet 2 times a day, if necessary, can be increased by 1/ tablets a day. As a rule, at the beginning of replacement therapy daily dose should not exceed 3 tablets per day (1 tablet 3 times a day). The application of this dosage is recommended in the early treatment of severe cases of parkinsonism. Daily dose of the drug in the form of exclusion may be increased in monotherapy, but should not exceed 8 tablets (1 tablet 8 times per day). Application in the amount of more than 6 tablets a day, should be done with great care.

The stop taking levodopa for 12 hours before treatment Singapoe, and in case of prolonged forms revocability for 24 hours Dosage Syndopa in this case should be no more than 20% from the previous dose of levodopa. The maintenance dose is 3-6 tablets per day for most patients.

Overdose

Symptoms: first, raising and then lowering blood pressure, sinus tachycardia, confusion, agitation, insomnia, anxiety. May also develop orthostatic hypotension. Anorexia and insomnia can persist for several days.

Treatment: gastric lavage, administration of activated charcoal. If necessary, symptomatic treatment in hospital. There is no specific antidote.

Drug interactions

— simultaneous administration with antihypertensive drugs requires special attention due to risk of postural hypotension,

— in a joint application with tricyclic antidepressants may experience hypertension and dyskinesia, as well decreases the bioavailability of levodopa,

— the combined use of phenothiazines, butyrophenones and Syntopy reduces the effect of the latter,

— Syndopa should not be administered with non-selective inhibitors of monoamine oxidase, as it can develop a hypertensive crisis. Treatment with monoamine oxidase inhibitors should be discontinued at least 14 days before prescribing. The exception is selegiline(a selective inhibitor of monoamine oxidase -b), which can be used as adjuvant in the treatment of levodopa,

— may increase the effects of sympathomimetics, it is recommended to reduce their dose. With simultaneous application of levodopa with ?-agonists, by means of inhalation anesthesia may increase the risk of cardiac arrhythmias,

— when the use of amantadine with levodopa marked potentiating effect

— methyldopa and levodopa can potenzirovti side effects of each other

— pyridoxine is a cofactor dofadekarboksilazy enzyme responsible for the peripheral decarboxylation of levodopa and a dopamine education. When administered to patients receiving levodopa (without inhibitors dofadekarboksilazy), there is increased peripheral metabolism of levodopa, and a smaller amount of it penetrates through the blood-brain barrier. Thus, pyridoxine reduces the therapeutic effect of the levodopa, if not further appointed inhibitors dofadekarboksilazy peripheral,

— with the appointment of additional inhibitors dofadekarboksilazy daily dose of levodopa can be reduced by 70-80% while maintaining the same clinical result

— the combined use of diazepam, phenytoin, clonidine, derivatives of thioxanthene, papaverine, reserpine, m-anticholinergics - may decrease anti-Parkinsonian actions.

Pregnancy and lactation

Contraindicated during pregnancy and lactation.

Side effects

From the nervous system: dyskinesia, including horeoatetoz, focal dystonia, prolonged use syndrome "on-off", dizziness, ataxia, convulsions, anorexia, sedation, drowsiness, nightmares, nervous tension, irritability, anxiety, insomnia, psychotic reaction, hallucinations, depression, paranoid state, hypomania, increased libido, euphoria, dementia.

Gastrointestinal tract: nausea, vomiting, constipation, epigastric pain, dysphagia, ulcerative in predisposed patients.

Of the cardiovascular system: orthostatic hypotension, collapse, cardiac arrhythmias, tachycardia.

With the hematopoietic system: mild leukopenia, thrombocytopenia, hemolytic anemia.

Laboratory parameters: changes in the level of glutamatdekarboksilazy, glutamatdekarboksilazy, alkaline phosphatase, lactate dehydrogenase, urea nitrogen, bilirubin, iodine-related protein, positive direct Coombs test.

Other: blepharospasm, mydriasis, diplopia, a slight increase of body weight with long-term use.

Side effects typically depend on the received dose, and individual sensitivity of the patient. Side effects can be eliminated by a temporary dose reduction without a break in the treatment. If side effects do not regress, the treatment should be stopped gradually.

Terms and conditions storage

Store in a dry, inaccessible for children and protected from light place at temperature not exceeding 30° C.

Shelf life - 4 years. Do not use after the expiry date printed on the package.

Testimony

— Parkinson's disease and the Parkinsonian syndrome of known etiology (due to encephalitis, cerebrovascular disorders, intoxication by toxic substances, including carbon monoxide or manganese).

Contraindications

— hypersensitivity to the drug,

— closure form of glaucoma,

— severe psychosis or neurosis,

— pregnancy and lactation,

— melanoma or suspected it,

— skin diseases of unknown etiology,

— Huntington's disease,

— essential tremor,

— secondary parkinsonism caused by use of antipsychotics (neuroleptics),

— child and adolescence to 18 years.

Caution: the drug is taken with caution when erosive-ulcerative lesions of the stomach and/or duodenum, seizures, a history of myocardial infarction with cardiac arrhythmias in history, heart failure, diabetes, bronchial asthma, diseases of the endocrine system, mental disorders, and in severe violations of the liver and kidneys.

Special instructions

It should not be used in cases of secondary parkinsonism (Parkinson's syndrome), caused by the use of antipsychotics (neuroleptics).

To stop treatment should be gradual, as the sudden discontinuation of the drug may develop the symptom complex resembling neuroleptic malignant syndrome (muscle rigidity, fever, elevated levels of creatine kinase in serum). Monitoring is required for patients who needed to suddenly reduce the dose or interrupt its reception. The absorption of levodopa in elderly patients is higher than the young. These data confirm data on reduced activity dofadekarboksilazy in tissues with age and with prolonged appointment of levodopa.

When erosive-ulcerative lesions of the stomach and/or duodenum, seizures, a history of myocardial infarction with arrhythmias, a history of heart failure, diabetes, bronchial asthma, diseases of the endocrine system, mental disorders, and in severe violations of the liver or kidneys to take the drug with caution. In such cases, patients should be closely monitored.

When prolonged treatment is necessary to perform periodic monitoring of liver function, kidneys, blood formation system and the cardiovascular system, also requires monitoring the mental status of the patient.

When General anesthesia during surgical operations Singapo shall not reduce the dose, if the patient is unable to take the drugs and the liquid inside. When using halothane and cyclopropane purpose of the drug is stopped at least 8 hours before surgery. Treatment continued after surgery in the same dose.

Patients with glaucoma on the background of the drug should regularly monitor the intraocular pressure.

Effects on ability to drive vehicles and management mechanisms

You should avoid driving and activities requiring speed of psychomotor reactions.

If impaired renal function

Use with caution in severe renal impairment.

When disorders of liver function

Use with caution in severe liver dysfunction.

The use in children

Contraindicated in childhood and adolescence to 18 years.