To Tidomet Forta

General characteristics. Structure:

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

Excipients: povidone (polyvinylpirrolidone), talc, magnesium stearate, starch (dry), silicon dioxide colloid, cellulose microcrystallic.

Pharmacological properties:

Pharmacodynamics. The structure of a levodopa represents the amino acid which is formed of L-tyrosine. Dopamine is formed directly of a levodopa with the participation of cytoplasmatic enzyme - a decarboxylase of aromatic L-amino acids. A net result of influence of dopamine is oppression of neyronalny activity in a striate body of a brain. The levodopa is quickly decarboxylized in peripheral fabrics under the influence of a decarboxylase of aromatic amino acids, dependent on a pyridoxine, turning into dopamine which, however, through a blood-brain barrier does not get.

Karbidopa inhibits process of decarboxylation of a levodopa in peripheral fabrics, at the same time does not get through a blood-brain barrier and does not influence transformation of a levodopa into dopamine in the central nervous system. Thus, the combination of a karbidopa and a levodopa allows to increase the quantity of a levodopa coming to a brain. At joint intake of a karbidop doubles bioavailability of a levodopa. Introduction of a karbidopa never leads to full oppression of a dofadekarboksilaza.

Pharmacokinetics. Levodopa. Absorption: The levodopa is soaked up by active transport from digestive tract, its passing through a blood-brain barrier is also carried out at the expense of active mechanisms. A barrier on the way of absorption of a levodopa is existence of a dofadekarboksilaza in an intestines wall. From a stomach the levodopa is absorbed in limited quantity. Speed of gastric emptying plays a key role in drug absorption. The factors which are slowing down gastric emptying (food, means m-holinoblokiruyushchiye), detain a drug passage in a duodenum and slow down its absorption. The maximum concentration of drug in blood is noted in 1-2 hours after introduction.
Distribution: The volume of distribution of a levodopa makes 0,9-1,6 l/kg. At preservation of activity of a dofadekarboksilaza the general clearance of a levodopa in a blood plasma makes 0,5 l/kg/h. The levodopa gets through a blood-brain barrier by the facilitated diffusion. The endothelium of capillaries of a brain also contains a dofadekarboksilaza as the second potential barrier on the way of receipt of a levodopa to a brain, however, in these capillaries an insignificant part of the entered levodopa dose is decarboxylized.

Metabolism: About 70-75% of the levodopa entered inside are metabolized in an intestines wall (effect of "the first passing"). The liver in metabolism of the first passing of participation practically does not accept. With increase in a dose of a levodopa the amount of the drug which is exposed to decarboxylation in intestines decreases. The levodopa does not contact proteins of a blood plasma. Decarboxylation of a levodopa a dopa-decarboxylase is the main way of formation of dopamine from a levodopa. A large amount of this enzyme is in intestines, a liver and kidneys. Metoksilirovany levodopas under influence catechol-au-methyltransferase with formation of 3-O-metildofy is the second way of metabolism of a levodopa. At prolonged treatment this metabolite can collect. Transamination is an additional way of metabolism of a levodopa. An end product of this way is ванилпируват, ванилацетат also 2,4,5-trigidroksifeniluksusny acid. All ways of metabolism, except for transamination, are irreversible.

Allocation: In a combination with karbidopy, the elimination half-life of a levodopa increases till 3 o'clock. To 69% of a levodopa it can be found in urine in the person in the form of dopamine and its metabolites – vinilinmindalny acid, noradrenaline, gomovanilinovy acid, dihydrophenylacetic acid.

Karbidopa. In the recommended doses of a karbidop does not get through a blood-brain barrier. The maximum concentration in a blood plasma is reached in 2-4 hours. About 50% of a karbidopa are removed with urine and a stake. 35% of the karbidopa which is removed kidneys are removed in an invariable look.

Indications to use:

Parkinson's disease and Parkinson's syndrome of the known etiology (owing to encephalitis, cerebrovascular disturbances, intoxication toxic substances, including monocarbon monoxide or manganese).

Route of administration and doses:

With a small amount of food or after food, washing down with water and not chewing. As there is a competition between aromatic amino acids and a levodopa at absorption, in usage time of drug it is necessary to avoid consumption of a large amount of proteins. The average day dose of a karbidopa necessary for suppression of peripheral transformation of a levodopa makes 70-100 mg. Exceeding of 200 mg of a karbidopa does not involve further strengthening of therapeutic effect. The daily dose of a levodopa should not exceed 2000 mg.

Initial dose – on 1/2 tablets 2 times a day, if necessary it is possible to increase by 1/2 tablets a day. As a rule, at the beginning of replacement therapy the day dose should not exceed 3 tablets a day (on the 1st tablet 3 times a day). Use in this dosage is recommended in an initiation of treatment of hard cases of parkinsonism. The daily dose of drug can be by way of exception increased at monotherapy, but should not exceed 8 tablets (on the 1st tablet of 8 times a day). Use in quantity of more than 6 tablets in day has to be carried out carefully.

To Tidomet Forta when replacing a levodopa. Reception of a levodopa is stopped in 12 hours prior to treatment by Tidomet Forte, and in case of reception of the prolonged levokarbidopa forms - in 24 hours. Tidomet Forte's dosage in this case has to make no more than 20% of a former dose of a levodopa. The maintenance dose makes 3-6 tablets a day for most of patients.

Features of use:

It is not necessary to apply in cases of secondary parkinsonism (Parkinson's syndrome) caused by use of antipsychotic means (neuroleptics).

It is necessary to stop treatment gradually as at the sudden termination of administration of drug development of the symptom complex reminding a malignant antipsychotic syndrome is possible (muscular rigidity, fervescence, increase in maintenance of KFK in blood serum). Control of patients who needed to lower suddenly a dose of drug is necessary or to interrupt its reception. Absorption of a levodopa at elderly patients is higher, than at young people. These data confirm data on decrease of the activity of a dofadekarboksilaza in fabrics with age, and also at long purpose of a levodopa.

At erosive cankers of a stomach and/or duodenum, epileptic seizures in the anamnesis, a myocardial infarction with disturbances of a rhythm in the anamnesis, heart failure, a diabetes mellitus, bronchial asthma, diseases of endocrine system, mental disturbances, and also at heavy abnormal liver functions or kidneys it is necessary to take drug with caution. Patients have to be in such cases under fixed observation of the doctor.

At long treatment it is necessary to exercise periodic control of function of a liver, kidneys, systems of a hemopoiesis and cardiovascular system, control of the mental status of the patient is also necessary.

At the general anesthesia when carrying out surgeries to Tidomet Forta appoint without reducing a dose if the patient is able to accept drugs and liquid inside. When using a halothane and cyclopropane purpose of drug is stopped at least in 8 hours prior to operation. Treatment is continued after operation in the same dose.

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

Influence on driving of vehicles: it is necessary to refrain from management of transport, and also the types of activity demanding speed of psychomotor reactions.

Side effects:

Nervous system: dyskinesia, including a choreoathetosis, focal dystonia, at prolonged use - a syndrome of "inclusion switching off", dizziness, an ataxy, spasms, anorexia, sedation, drowsiness, dreadful dreams, nervous tension, a hyperexcitability, concern, sleeplessness, psychotic reactions, hallucinations, a depression, paranoid states, a hypomania, the raised libido, euphoria, dementia.

Digestive tract: a loss of appetite, nausea, vomiting, a lock, pains in epigastriums, a dysphagy, ulcerogenic action at predisposed patients.

Cardiovascular system: orthostatic hypotension, collapse, cardiac arrhythmias, tachycardia.

System of a hemopoiesis: moderate leukopenia, thrombocytopenia, hemolitic anemia.

Change of laboratory indicators: change of level of a glutumatoksalattransaminaza, glutamatpiruvatoksalaza, alkaline phosphatase, lactate dehydrogenase, urea nitrogen, bilirubin, the iodine connected with protein, positive forward reaction of Koombs.

Other: a nictitating spasm, a mydriasis, a diplopia, insignificant increase in body weight at prolonged use.

Side effects, as a rule, depend on the accepted dose, and also on individual sensitivity of the patient. Side effects can be eliminated with a temporary dose decline without interruption in treatment. If side effects do not regress, then stop treatment gradually.

Interaction with other medicines:

• co-administration with antihypertensives requires special attention in connection with danger of postural hypotension.
• at combined use with tricyclic antidepressants there can be arterial hypertension and dyskinesia, bioavailability of a levodopa also decreases.
• the combined use of fenotiazin, phenyl propyl ketones and Tidomet Forte reduces effect of the last.
• To Tidomet Forta it should not be appointed together with non-selective inhibitors of a monoaminooxidase as hypertensive crisis can develop. Treatment by inhibitors of a monoaminooxidase has to be stopped, at least, in 14 days prior to purpose of drug. The exception makes селегилин (selective inhibitor of a monoaminooxidase – In) which can be used as adjuvant at treatment by a levodopa.
• can strengthen action of sympathomimetics in this connection it is recommended to lower their dose. At simultaneous use of a levodopa with β-adrenostimulyator, means for inhalation anesthesia increase in risk of development of disturbances of a cordial rhythm is possible.
• at use of an amantadin with a levodopa the exponential effect is noted.
• Methyldopa and a levodopa can exponentiate side effects of each other.
• the pyridoxine is a dofadekarboksilaza cofactor – the enzyme responsible for peripheral decarboxylation of a levodopa and formation of dopamine. At its appointment as the patient receiving a levodopa (without dofadekarboksilaza inhibitors), strengthening of peripheral metabolism of a levodopa is noted and its smaller quantity gets through a blood-brain barrier. Thus, the pyridoxine reduces therapeutic effect of a levodopa if inhibitors of a peripheral dofadekarboksilaza in addition are not appointed.
• at additional purpose of inhibitors of a dofadekarboksilaza the daily dose of a levodopa can be reduced by 70-80% at preservation of the same clinical result.
• at combined use with diazepam, Phenytoinum, clonidine, thioxanthene derivatives, a papaverine, Reserpinum, M-holinoblokatorami reduction of protivoparkinsonichesky action is possible.
• at simultaneous use with drugs of lithium (Li+) the risk of development of diskineziya and hallucinations increases.

Contraindications:

Hypersensitivity to drug, a closed-angle form of glaucoma, heavy psychosis or neurosis, pregnancy and a lactation, a melanoma or suspicion on it, skin diseases of an unknown etiology, Huntington disease, an essential tremor. It is not necessary to apply to treatment of the secondary parkinsonism caused by use of antipsychotic means (neuroleptics). It is not recommended to appoint the patient up to 18 years.

With care. Drug is taken with caution at erosive cankers of a stomach and/or duodenum, epileptic seizures in the anamnesis, a myocardial infarction with disturbances of a heart rhythm in the anamnesis, heart failure, a diabetes mellitus, bronchial asthma, diseases of endocrine system, mental disturbances, and also at heavy abnormal liver functions and kidneys.

Overdose:

Symptoms: at first increase, and then lowering of arterial pressure, sinus tachycardia, confusion of consciousness, excitement, sleeplessness, concern. Orthostatic hypotension can also develop. Symptoms of anorexia and sleeplessness can remain within several days.

Treatment: gastric lavage, reception of absorbent carbon. If necessary carrying out a symptomatic treatment in the conditions of a hospital. The specific antidote does not exist.

Storage conditions:

Period of validity - 3 years. Not to use after the expiry date specified on packaging. To store at a temperature not above 30 °C in the dry, protected from light place unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets. 10 tablets in a strip from aluminum foil. 10 strips in a cardboard pack together with the application instruction. A sample not for sale: 4 or 10 tablets in a strip from aluminum foil. 1 strip with the application instruction in a cardboard pack.