Composition, form of production and packaging
Tablets 1 tab.
levodopa 250 mg
carbidopa 25 mg
10 pieces. - packings cellular planimetric (10) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
The structure of levodopa is an amino acid formed from L-tyrosine. Dopamine is formed directly from levodopa with the participation of the cytoplasmic enzyme - decarboxylase of aromatic L-amino acids. The end result of dopamine is the inhibition of neuronal activity in the striatum of the brain.
Levodopa is rapidly decarboxylated in peripheral tissues under the influence of aromatic amino acids dependent on pyridoxine decarboxylase, turning into dopamine, which, however, does not penetrate the blood-brain barrier.
Carbidopa inhibits the decarboxylation process of levodopa in peripheral tissues, without penetrating the blood-brain barrier and does not affect the conversion of levodopa to dopamine in the central nervous system. Thus, the combination of carbidopa and levodopa increases the amount of levodopa that enters the brain. When combined ingestion of carbidopa doubles the bioavailability of levodopa. The introduction of carbidopa never leads to complete inhibition of dofadecarboxylase.
PHARMACOKINETICS
Levodopa
Suction
Levodopa is absorbed by active transport from the gastrointestinal tract, its passage through the blood-brain barrier is also carried out through active mechanisms. The barrier to absorption of levodopa is the presence of dofadecarboxylase in the intestinal wall. From the stomach, levodopa is absorbed in a limited amount. The rate of gastric emptying plays a key role in the absorption of the drug. Factors that slow gastric emptying (food, m-holinoblokiruyuschie funds), delay the passage of the drug in the duodenum and slow its absorption. C max drug in the blood is noted 1-2 hours after administration.
Distribution
V d of levodopa is 0.9-1.6 l / kg. If the activity of dofadecarboxylase is maintained, the total clearance of levodopa in the blood plasma is 0.5 l / kg / h. Levodopa penetrates the blood-brain barrier by facilitated diffusion. The endothelium of the capillaries of the brain also contains dopadecarboxylase as the second potential barrier to the passage of levodopa into the brain, however, in these capillaries an insignificant part of the administered dose of levodopa is decarboxylated.
Metabolism
Approximately 70-75% of the administered levodopa is metabolized in the intestinal wall (the effect of "first passage"). Liver in the metabolism of the first passage of participation is almost not accepted. With increasing doses of levodopa, the amount of the drug that undergoes decarboxylation in the intestine decreases. Levodopa does not bind to blood plasma proteins. Decarboxylation of levodopa with dofadecarboxylase is the main way of formation of dopamine from levodopa. A large amount of this enzyme is found in the intestines, liver and kidneys. Methoxylation of levodopa under the influence of catechol-O-methyltransferase to form 3-O-methyldopa is the second way of metabolizing levodopa. With long-term treatment, this metabolite can accumulate. Transamination is an additional way of metabolizing levodopa. The final product of this route is vinyl pyruvate, vinyl acetate and 2,4,5-trihydroxyphenylacetic acid. All metabolic pathways, with the exception of transamination, are irreversible.
Allocation
In combination with carbidopa, T 1/2 levodopa increases to 3 hours. Up to 69% of levodopa can be found in the urine of a person in the form of dopamine and its metabolites - vanillinmendal acid, noradrenaline, homovanilic acid, dihydrophenylacetic acid.
Carbidopa
In recommended doses, carbidopa does not penetrate the blood-brain barrier. C max in blood plasma is reached after 2-4 hours. Approximately 50% of carbidopa is excreted in urine and feces. 35% of carbidopa with excretory buds, is excreted unchanged.
INDICATIONS
- Parkinson's disease and parkinsonian syndrome of known etiology (due to encephalitis, cerebrovascular disorders, intoxication with toxic substances, including carbon monoxide or manganese).
DOSING MODE
Inside, with a small amount of food or after a meal, washing down with water and not chewing. Since there is competition between aromatic amino acids and levodopa during absorption, during the use of the drug, a large number of proteins should be avoided. The average daily dose of carbidopa, necessary to suppress peripheral conversion of levodopa, is 70-100 mg. Excess of 200 mg of carbidopa does not entail a further increase in the therapeutic effect. The daily dose of levodopa should not exceed 2000 mg. The initial dose is 1/2 tablet. 2 times / day, if necessary, you can increase by 1/2 tab. / Day. As a rule, at the beginning of replacement therapy, the daily dose should not exceed 3 tab. / Day (1 tab. 3 times / day). Use in this dosage is recommended at the beginning of treatment of severe cases of Parkinsonism. The daily dose of the drug as an exception can be increased with monotherapy, but should not exceed 8 tab. (1 tablet 8 times / day). Use in quantities of more than 6 tablets / day should be done with great care.
SIDE EFFECT
From the side of the central nervous system: dyskinesia, incl. choreoathetosis, dystonia, with prolonged use of the "on-off" syndrome, malignant neuroleptic syndrome, dizziness, ataxia / nausea, dystonic involuntary movements, convulsions, anorexia, sedation, drowsiness, confusion, nightmares, nervous tension, increased excitability, anxiety, insomnia; changes in mental status, including paranoid effects and transient psychoses; hallucinations, depression with or without development of suicidal intentions, hypomania, increased libido, euphoria, dementia. The basis for the decision to reduce the dose of the drug can serve as early symptoms, such as muscle twitches and blepharospasm. The development of seizures has been reported, but no direct connection with the use of carbidopa / levodopa has been established.
On the part of the digestive system: anorexia, nausea, vomiting, constipation, epigastric pain, dysphagia, darkening of saliva, ulcerogenic effect in predisposed patients; rarely - gastrointestinal bleeding.
From the side of the cardiovascular system: orthostatic hypotension, collapse, arrhythmias, tachycardia, arterial hypertension, phlebitis.
From the hemopoietic system: rarely - leukopenia, anemia (including hemolytic), thrombocytopenia, agranulocytosis.
Allergic reactions: angioedema, urticaria, skin rash, skin itching, Shenlen-Henoch disease.
Change in laboratory indicators: changes in the level of ALT, AST, APF, LDH, urea nitrogen, bilirubin, iodine, protein-bound, hyperuricemia, hypercreatinemia, positive direct Coombs test.
Other: syncopal conditions, chest pain, mydriasis, diplopia, dyspnoea, darkening of secretion of sweat glands, darkening of urine, increase or decrease in body weight.
Side effects, as a rule, depend on the dose taken, as well as on the individual sensitivity of the patient. Side effects can be eliminated by a temporary dose reduction without interruption in treatment. If the side effects do not regress, then the treatment is stopped gradually.
Other side effects that have occurred with the administration of levodopa, which should be considered when using carbidopa / levodopa:
On the part of the digestive system: dyspepsia, dry mouth, bitterness in the mouth, sialorrhea, dysphagia, bruxism, bouts of hiccough, pain and discomfort in the abdomen, constipation, flatulence, burning sensation of the tongue.
From the side of metabolism: decrease or increase in body weight, swelling.
From the side of the central nervous system: weakness, fainting, fatigue, headache, asthenia, decreased mental activity, disorientation, ataxia, numbness, increased tremor of hands, muscle cramps, trismus, activation of latent Bernard-Horner syndrome, insomnia, anxiety, euphoria, psychomotor agitation , instability of gait.
On the part of the senses: diplopia, blurred vision, dilated pupils, oculogic crises.
From the urinary system: urinary retention, urinary incontinence, priapism.
Other: hoarseness of voice, malaise, "hot flashes" of blood to the skin of the face, neck and chest, dyspnoea, malignant melanoma. There was reported a decrease in hemoglobin and hematocrit, hyperglycemia, leukocytosis, bacteriuria, erythrocyturia.
Laboratory indicators: drugs containing carbidopa / levodopa may cause a false positive reaction to ketone bodies in the urine if test strips are used to determine ketonuria. This reaction will not change after boiling urine samples. False negative results can be obtained by using a glucose oxidase method for determining glucosuria.
CONTRAINDICATIONS
- the closed-angle form of glaucoma;
- severe psychosis or neurosis;
melanoma or suspicion of it;
- skin diseases of unknown etiology;
Huntington's disease;
- Essential tremor;
- simultaneous reception of non-selective MAO inhibitors, an interval of less than 2 weeks after the end of MAO inhibitors;
- Pregnancy;
- lactation;
- Hypersensitivity to the drug.
It should not be used for the treatment of secondary parkinsonism caused by the use of antipsychotics (neuroleptics). It is not recommended to appoint patients under 18 years.
With caution, the drug is taken with erosive and ulcerative lesions of the stomach and / or duodenum, epileptic seizures in the anamnesis, severe cardiovascular diseases (including myocardial infarction with heart rhythm disorders in the anamnesis, heart failure), diseases of the endocrine system including diabetes mellitus), severe lung diseases (including bronchial asthma), mental disorders, as well as severe violations of the liver and kidneys.
PREGNANCY AND LACTATION
Contraindicated during pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
Carefully.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Carefully.
APPLICATION FOR CHILDREN
It is not recommended to appoint patients under 18 years.
APPLICATION IN ELDERLY PATIENTS
Absorption of levodopa in elderly patients is higher than in young patients. These data confirm the information about the decrease in the activity of dofadecarboxylase in tissues with age, as well as with the long-term administration of levodopa.
SPECIAL INSTRUCTIONS
It should not be used in cases of secondary parkinsonism (Parkinson's syndrome) caused by the use of antipsychotics (neuroleptics).
Stop treatment should be gradual, tk. with a sudden discontinuation of the drug may develop a symptom complex resembling a malignant neuroleptic syndrome (muscle rigidity, fever, increased serum levels of CK).
It is necessary to monitor patients who suddenly needed to lower the dose of the drug or interrupt its reception.
Absorption of levodopa in elderly patients is higher than in young patients. These data confirm the information about the decrease in the activity of dofadecarboxylase in tissues with age, as well as with the long-term administration of levodopa.
With erosive and ulcerative lesions of the stomach and / or duodenum, epileptic seizures in the history, severe cardiovascular diseases (including myocardial infarction with heart rhythm disorders in the anamnesis, heart failure), diseases of the endocrine system (including diabetes mellitus), severe lung diseases (including bronchial asthma), mental disorders, as well as severe violations of the liver and kidneys should be taken with caution. In such cases, patients should be closely monitored.
With prolonged treatment, periodic monitoring of liver, kidney, hemopoietic system and cardiovascular system is necessary, as well as monitoring of the patient's mental status.
When performing surgical operations, if general anesthesia is required, Carbidopa / Levodopa is prescribed without lowering the dose until the patient can take drugs and liquid inside. When using halothane and cyclopropane, the drug is discontinued at least 8 hours prior to surgery. Treatment continues after the operation in the same dose. Patients with glaucoma against the background of taking the drug should regularly monitor the intraocular pressure.
Impact on the ability to drive vehicles and manage mechanisms
It is necessary to refrain from the management of transport, as well as activities requiring rapidity of psychomotor reactions.
OVERDOSE
Symptoms: first an increase, then a decrease in blood pressure, sinus tachycardia, a disturbance of the heart rhythm, confusion, agitation, anorexia, insomnia, anxiety.Orthostatic hypotension may also develop. Symptoms of anorexia and insomnia may persist for several days.
Treatment: symptomatic. Gastric lavage, reception of activated charcoal, if necessary, symptomatic treatment in a hospital. There is no specific antidote. Pyridoxine does not remove the action of the drug. Currently, there is no data on the use of dialysis, it is necessary to monitor heart activity in order to prevent the development of arrhythmias.
DRUG INTERACTION
Simultaneous appointment with hypotensive drugs requires special attention in connection with the danger of postural hypotension.
When combined with tricyclic antidepressants, arterial hypertension and dyskinesia may occur, as does the bioavailability of levodopa.
The combined use of phenothiazines, butyrophenones and carbidopa / levodopa reduces the effect of the latter.
Carbidopa / levodopa can not be administered together with nonselective MAO inhibitors, may develop a hypertensive crisis. Treatment with MAO inhibitors should be discontinued at least 14 days before the start of the drug administration. The exception is selegilin (selective MAO-B inhibitor) which can be used as an adjuvant in the treatment with levodopa.
May enhance the effect of sympathomimetics, in this connection, it is recommended to reduce their dose. With the simultaneous use of levodopa with 8-adrenergic stimulants, the means for inhalation anesthesia may increase the risk of heart rhythm disturbances.
When using amantadine with levodopa, a mutually potentiating effect is noted.
Methyldopa and levodopa can potentiate the side effects of each other.
Pyridoxine is a cofactor of dofadecarboxylase, an enzyme responsible for the peripheral decarboxylongonation of levolopa and the formation of dopamine. When he is prescribed to patients receiving levodopa (without inhibitors of dopadecarboxylase), there is an increase in peripheral metabolism of levodopa and a smaller amount of it penetrates the blood-brain barrier. Thus, pyridoxine reduces the therapeutic effect of levodopa unless additional inhibitors of peripheral dofadecarboxylase are prescribed.
With the additional appointment of dopadecarboxylase inhibitors, the daily dose of levodopa can be reduced by 70-80% while maintaining the same clinical result.
Joint use with diazepam, phenytoin, clonidine, thioxanthene derivatives, papaverine, reserpine, m-holinoblokatorami - may reduce the antiparkinsonian action.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Store in a dry, dark place at a temperature of no higher than 25 В° C. Keep out of the reach of children.
Shelf life - 5 years.
Do not use after the expiration date printed on the package.
