The use of levodopa and its effect on the body. Use in children
P N013777/01-090608Tradename: Carbidopa/Levodopa
PIM or grouping name: Levodopa + Carbidopa
Dosage form:
tabletsCompound
active substances: 250 mg levodopa 25 mg carbidopa (27 mg as monohydrate)
Excipients: povidone, microcrystalline cellulose, sodium carboxymethyl starch, colloidal silicon dioxide, magnesium stearate, purified talc, brilliant blue dye E133, sunset yellow dye E110, disodium edetate, glycerol.
Description
Tablets are oval, biconvex, light blue in color, with lighter or darker patches, scored on one side and the manufacturer's logo on the other side.
Pharmacotherapeutic group:
antiparkinsonian agent (dopamine precursor + peripheral decarboxylase inhibitor)
CodeATH: Pharmacological properties
Pharmacodynamics
The structure of levodopa is an amino acid derived from L-tyrosine. Dopamine is formed directly from levodopa with the participation of a cytoplasmic enzyme, aromatic L-amino acid decarboxylase. The end result of the influence 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 pyridoxine-dependent aromatic amino acid decarboxylase, turning into dopamine, which, however, does not penetrate the blood-brain barrier. Carbidopa inhibits the process of decarboxylation of levodopa in peripheral tissues, while it does not penetrate 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 allows you to increase the amount of levodopa that enters the brain. When taken together, carbidopa doubles the bioavailability of levodopa. The introduction of carbidopa never leads to complete inhibition of dopa decarboxylase.
Pharmacokinetics
a./Levodopa
ABSORBATION: Levodopa is absorbed by active transport from the gastrointestinal tract, its passage through the blood-brain barrier is also carried out by active mechanisms. A barrier to the absorption of levodopa is the presence of dopa decarboxylase in the intestinal wall. From the stomach, levodopa is absorbed in a limited amount. The rate of gastric emptying plays a key role in drug absorption. Factors that slow down gastric emptying (food, m-anticholinergics), delay the passage of the drug into the duodenum and slow down its absorption. The maximum concentration of the drug in the blood is observed 1-2 hours after administration.
DISTRIBUTION: The volume of distribution of levodopa is 0.9-1.6 l/kg. While maintaining the activity of dopa decarboxylase, the total clearance of levodopa in blood plasma is 0.5 l / kg / hour. Levodopa crosses the blood-brain barrier by facilitated diffusion. The endothelium of the capillaries of the brain also contains dopa decarboxylase as the second potential barrier to the entry of levodopa into the brain, however, an insignificant part is decarboxylated in these capillaries.
METABOLISM: Approximately 70-75% of oral levodopa is metabolized in the intestinal wall ("first pass" effect). The liver practically does not take part in the metabolism of the first passage. With an increase in the dose of levodopa, the amount of the drug undergoing decarboxylation in the intestine decreases. Levodopa does not bind to plasma proteins. Decarboxylation of levodopa by dopa decarboxylase is the main pathway for the 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 with the formation of 3-O-methyldopa is the second pathway of levodopa metabolism. With prolonged treatment, this metabolite may accumulate. Transamination is an additional pathway for the metabolism of levodopa. The end product of this pathway is vinyl pyruvate, vinyl acetate, and 2,4,5-trihydroxyphenylacetic acid. All metabolic pathways, with the exception of transamination, are irreversible.
RELEASE: In combination with carbidopa, the elimination half-life of levodopa is increased to 3 hours. Up to 69% of levodopa can be found in human urine in the form of dopamine and its metabolites - vanillinmandelic acid, norepinephrine, homovanillic acid, dihydrophenylacetic acid.
b./Carbidopa
At recommended doses, carbidopa does not cross the blood-brain barrier. The maximum plasma concentration is reached after 2-4 hours. Approximately 50% of carbidopa is excreted in urine and feces. 35% of carbidopa excreted by the kidneys is excreted unchanged.
Indications for use
Parkinson's disease and parkinsonism syndrome of known etiology (due to encephalitis, cerebrovascular disorders, intoxication with toxic substances, including carbon monoxide or manganese).
Contraindications
It should not be used to treat secondary parkinsonism caused by the use of antipsychotics (neuroleptics). Not recommended for patients under 18 years of age. Carefully
The drug is taken with caution in case of erosive and ulcerative lesions of the stomach and / or duodenum, epileptic seizures in history, severe diseases of the cardiovascular system (including myocardial infarction with a history of heart rhythm disturbances, 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. Dosage and administration
Inside, with a small amount of food or after eating, drinking water and not chewing. Since there is competition between aromatic amino acids and levodopa during absorption, the consumption of large amounts of proteins should be avoided during the use of the drug. The average daily dose of carbidopa required to suppress the peripheral conversion of levodopa is 70-100 mg. Exceeding 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 a day, if necessary, can be increased by 1/2 tablet a day. As a rule, at the beginning of replacement therapy, the daily dose should not exceed 3 tablets per day (1 tablet 3 times a day). Use at this dosage is recommended at the start of treatment for severe cases of parkinsonism. The daily dose of the drug, as an exception, can be increased with monotherapy, but should not exceed 8 tablets (1 tablet 8 times a day). The use of more than 6 tablets per day should be carried out with great caution. Side effect
Nervous system: dyskinesia, including choreoathetosis, dystonia, with prolonged use, "on-off" syndrome, neuroleptic malignant syndrome, dizziness, ataxia, nausea, dystonic involuntary movements, convulsions, anorexia, sedation, drowsiness, confusion, nightmares, nervous tension, irritability, anxiety, insomnia; mental status changes, including paranoid effects and transient psychoses; hallucinations, depression with or without suicidal ideation, hypomania, increased libido, euphoria, dementia. Early symptoms such as muscle twitching and blepharospasm can serve as the basis for the decision to reduce the dose of the drug. Seizures have been reported, but no direct association with carbidopa/levodopa has been established.
Gastrointestinal tract: anorexia, nausea, vomiting, constipation, epigastric pain, dysphagia, darkening of saliva, ulcerogenic effect in predisposed patients; rarely - gastrointestinal bleeding.
The cardiovascular system: orthostatic hypotension, collapse, arrhythmias, tachycardia, arterial hypertension, phlebitis.
Hematopoietic system: rarely - leukopenia, anemia (including hemolytic), thrombocytopenia, agranulocytosis.
Allergic reactions: angioedema, urticaria, skin rash, skin itching, Shenlein-Genoch disease.
Change in laboratory parameters: change in the level of alanine amino transferase, aspartate amino transferase, alkaline phosphatase, lactate dehydrogenase, urea nitrogen, bilirubin, protein-bound iodine, hyperuricemia, hypercreatinemia, positive direct Coombs test.
Other: syncopal conditions, chest pain, mydriasis, diplopia, dyspnea, darkening of the secretion of sweat glands, darkening of urine, weight gain or decrease.
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 temporarily reducing the dose without interrupting treatment. If the side effects do not regress, then the treatment is stopped gradually. Other side effects that have occurred while taking LEVODOPA, which should be considered in the case of the use of the drug carbidopa / levodopa:
Gastrointestinal tract: dyspepsia, dry mouth, bitterness in the mouth, sialorrhea, dysphagia, bruxism, hiccups, pain and discomfort in the abdomen, constipation, flatulence, burning sensation of the tongue.
Metabolism: decrease or increase in body weight, edema.
CNS: Weakness, fainting, fatigue, headache, asthenia, decreased mental activity, disorientation, ataxia, numbness, increased hand tremor, muscle cramps, trismus, activation of the latent Bernard-Horner syndrome, insomnia, anxiety, euphoria, psychomotor agitation, instability gait. Sense organs: diplopia, blurred vision, dilated pupils, oculogyric crises.
Urogenital system: urinary retention, urinary incontinence, priapism.
Other side effects: hoarseness, malaise, flushing of the skin of the face, neck and chest, dyspnea, malignant melanoma. Decreased hemoglobin and hematocrit, hyperglycemia, leukocytosis, bacteriuria, erythrocyturia have been reported.
Altered Laboratory Values: Drugs containing carbidopa-levodopa may cause a false positive reaction for urinary ketone bodies when dipstick tests are used to detect ketonuria. This reaction will not change after boiling urine samples. False-negative results can be obtained using the glucose oxidase method for determining glycosuria. Overdose
Symptoms: first increase and then decrease in blood pressure, sinus tachycardia, heart rhythm disturbance, confusion, agitation, anorexia, insomnia, anxiety. Orthostatic hypotension may also develop. Symptoms of anorexia and insomnia may persist for several days.
Treatment: symptomatic. Gastric lavage, activated charcoal, if necessary, symptomatic treatment in a hospital. There is no specific antidote. Pyridoxine does not remove the effect of the drug. Currently there are no data on the use of dialysis It is necessary to monitor the activity of the heart in order to prevent the development of arrhythmias. Interaction with other drugs
It should not be used in cases of secondary parkinsonism (Parkinson's syndrome) caused by the use of antipsychotics (neuroleptics).
Treatment should be stopped gradually, since with a sudden cessation of taking the drug, a symptom complex resembling neuroleptic malignant syndrome (muscle rigidity, fever, increased serum CPK) may develop. It is necessary to monitor patients who need to suddenly reduce the dose of the drug or stop taking it. Absorption of levodopa in elderly patients is higher than in young patients. These data confirm the information about the decrease in the activity of dopa decarboxylase in tissues with age, as well as with long-term administration of levodopa.
With erosive and ulcerative lesions of the stomach and / or duodenum, epileptic seizures in history, severe diseases of the cardiovascular system (including myocardial infarction with a history of heart rhythm disturbances, 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 kidney function, the drug should be taken with caution. In such cases, patients should be closely monitored.
With prolonged treatment, it is necessary to periodically monitor the function of the liver, kidneys, hematopoietic and cardiovascular systems, and it is also necessary to monitor the patient's mental status.
During surgical operations, if general anesthesia is required, the drug Carbidopa / Levodopa is prescribed without reducing the dose, as long as the patient can take drugs and liquids by mouth. When using halothane and cyclopropane, the drug is discontinued at least 8 hours before surgery. Treatment is continued after surgery at the same dose. Patients with glaucoma while taking the drug should regularly monitor intraocular pressure. Impact on driving motor vehicles:
it is necessary to refrain from driving, as well as activities that require the speed of psychomotor reactions. Release form
Tablets 25 mg+250 mg
10 tablets in a blister of PVC film and aluminum foil. 10 blisters, together with instructions for use, are placed in a cardboard box. Storage conditions
In a dry, dark place, at a temperature not exceeding 25 ° C.
Keep out of the reach of children. Best before date
5 years.
Do not use after the expiry date stated on the package. Terms of dispensing from pharmacies
On prescription.
Manufacturer:
Pharmaceutical plant "Remedica Ltd", Cyprus. /Manufacturers of pharmaceuticals "Remedica Ltd", Cyprus/.
For product quality complaints, please contact:
Pharmimex JSC Russian Federation, Moscow, st. Bolshaya Dimitrovka, d. 7/5, building 5;
Photo of the preparation
Latin name: Levodopa / Benserazide-Teva
ATX Code: N04BA
Active substance: Levodopa + Benserazide (Levodopa + Benserazide)
Manufacturer: Pharmaceutical plant Teva Private Co. Ltd., Hungary
The description applies to: 14.12.17
Levodopa Benserazide is an antiparkinsonian drug.
Active substance
Levodopa + Benserazide (Levodopa + Benserazide).
Release form and composition
Levodopa Benserazide is sold in the form of tablets. The medicinal product is produced in polyethylene bottles (20, 30, 50, 60 or 100 tablets each) placed in cardboard packages of 1 pc.
Indications for use
The indication for the appointment of a medication is Parkinson's disease.
Contraindications
Contraindications to the use of the drug are:
- Severe functional disorders of the liver and / or kidneys.
- Exogenous and endogenous psychoses.
- Severe functional disorder of the endocrine system.
- Glaucoma.
- Women of childbearing age not using reliable methods of contraception.
- Severe functional impairment of the cardiovascular system.
- The period of pregnancy and breastfeeding.
- Co-administration with non-selective MAO inhibitors.
- The patient's age is up to 25 years.
- Hypersensitivity to benserazide, levodopa or other auxiliary components.
Instructions for use Levodopa Benserazide (method and dosage)
The drug is intended for oral use. Tablets should be taken half an hour before or one hour after meals with a small amount of liquid.
Treatment should begin with a minimum dose, gradually increasing until the desired therapeutic effect is achieved. It is not recommended to take large doses of the drug.
For patients who have not previously taken levodopa, the drug is prescribed 50 mg levodopa / 12.5 mg benserazide 2-4 times a day. If the patient responds normally to ongoing therapy, it is possible to increase the dosage of the drug to 100 mg of levodopa / 25 mg of benserazide, which are taken every three days until the desired effect is achieved.
The maximum allowable daily dosage is 800 mg for levodopa and 200 mg for benserazide.
In the event of an adverse reaction, it is necessary to reduce the dosage of the drug or completely cancel this drug.
Patients who have previously taken levodopa should start taking this drug 12 hours after stopping levodopa. The dosage should be approximately 20% of the previously taken dose of levodopa.
Patients with Parkinson's disease who have previously taken levodopa in combination with an aromatic L-amino acid decarboxylase inhibitor should start taking it 12 hours after stopping previous therapy. To prevent a decrease in the effectiveness of treatment, treatment should be stopped at night, and Levodopa Benserazide should be started the next morning.
Dosing regimens in special cases
Patients experiencing strong motor fluctuations should take the drug more than 4 times a day in compliance with the daily dosage.
Elderly people should increase the dosage very slowly.
Patients with mild to moderate renal and hepatic insufficiency do not require dose adjustment.
In the event of spontaneous movements (atetosis or chorea) or the appearance of a negative reaction from the cardiovascular system, it is recommended to reduce the daily dosage.
Side effects
The use of the drug can cause the following side effects:
- Central nervous system: often - episodes of "freezing", headache, "on-off" phenomenon, dizziness, weakening of the effect by the end of the dose, convulsions, increased symptoms of restless legs syndrome, spontaneous movement disorders (such as athetosis and chorea) ; sometimes - episodes of sudden drowsiness, severe drowsiness.
- Cardiovascular system: sometimes - increased blood pressure, orthostatic hypotension (weakens after lowering the dose of the drug), arrhythmias; frequency unknown - "hot flashes".
- Hematopoietic system: sometimes - thrombocytopenia, transient leukopenia, hemolytic anemia.
- Digestive system: sometimes - attacks of nausea, diarrhea, vomiting, dryness of the oral mucosa, individual cases of changes or loss of taste sensations; frequency unknown - bleeding in the gastrointestinal tract.
- Subcutaneous tissues and skin: rarely - skin rashes, itching.
- Mental disorders: rarely - insomnia, agitation, increased libido, anxiety, anorexia, depressed mood, hypersexuality, delirium, pathological gambling, moderate enthusiasm, depression, aggression; sometimes - temporary disorientation, hallucinations.
- Laboratory indicators: infrequently - an increase in the concentration of bilirubin, alkaline phosphatase, creatinine and urea in the blood, a transient increase in the activity of liver enzymes, a change in the color of urine to red (it may darken when standing).
- Other: frequency unknown - excessive sweating, febrile fever.
Overdose
Overdose symptoms: increased manifestation of negative reactions - pathological involuntary movements, insomnia, arrhythmia, nausea and vomiting, confusion. The development of signs of overdose may be delayed as a result of delayed absorption of the drug from the gastrointestinal tract.
As a treatment, symptomatic therapy is used, which consists in taking antipsychotics, antiarrhythmic drugs and respiratory analeptics.
Analogues
Analogues according to the ATX code: Levodopa + Benserazide, Madopar.
Do not make the decision to change the drug yourself, consult your doctor.
pharmachologic effect
Levodopa Benserazide is a combined drug that has an antiparkinsonian effect. It contains a dopamine precursor and an inhibitor of peripheral decarboxylase aromatic L-amino acids.
In Parkinson's disease, dopamine is not synthesized in sufficient quantities and this drug is used as a replacement therapy. The main part of levodopa is transformed into dopamine in peripheral tissues, which does not have an anti-Parkinsonian effect. To enhance the effect of this substance, the drug is supplemented with benserazide.
special instructions
Undesirable manifestations from the organs of the gastrointestinal tract (occur at the initial stage of therapy) are largely eliminated with a slower increase in the dose, and also if the tablets are taken with a small amount of liquid or taken with food. It is not desirable to use the drug for the treatment of Huntington's chorea and iatrogenic extrapyramidal syndrome.
People with a history of osteomalacia, gastrointestinal ulcers and convulsions should be regularly analyzed for relevant indicators. During therapy, it is necessary to monitor the functional parameters of the kidneys, liver, blood count. Patients with a history of cardiac arrhythmias, myocardial infarction, coronary heart disease should regularly undergo electrocardiogram monitoring.
Patients with a history of orthostatic hypotension should be closely monitored by a specialist, especially at the start of treatment.
Patients with diabetes need to frequently adjust the dose of oral hypoglycemic agents and monitor blood glucose levels. When using Levodopa Benserazide, there were reports of cases of sudden onset of sleep. Patients should be informed about this.
When using the drug, the risk of malignant melanoma increases. In this regard, taking pills in people with this disease (including a history) is not desirable. The use of this drug, especially at high doses, increases the chance of developing compulsive disorders.
Levodopa Benserazide should not be stopped abruptly. This can provoke a "withdrawal syndrome" (muscle rigidity, fever, as well as a possible increase in the activity of creatinine phosphokinase in the blood and mental changes) or an akinetic crisis, which can take a life-threatening form. If such signs appear, the patient should be under the close supervision of a specialist (if necessary, hospitalization is carried out) and receive appropriate treatment. Sometimes it is advisable to reuse Levodopa Benserazide.
Before general anesthesia, the medication should be taken for as long as possible. An exception is halothane anesthesia. Since a patient receiving Levodopa Benserazide may develop arrhythmias and fluctuations in blood pressure during halothane anesthesia, the drug should be discontinued 12-24 hours before surgery. After surgery, therapy is resumed, gradually increasing the dose.
Some people with Parkinson's disease have developed cognitive and behavioral disorders due to uncontrolled use of increasing doses of the drug (despite a significant increase in therapeutic doses and doctor's recommendations).
During therapy with Levodopa Benserazide, depression may occur. It can also be a clinical symptom of the underlying disease (parkinsonism). Such people should be under the supervision of a doctor for the timely detection of mental adverse reactions.
Experience with the use of the drug before the age of 25 years is limited.
Patients who experience sudden episodes of sleep or excessive daytime sleepiness are required to stop driving or operating complex machinery. If these signs occur during therapy, it is advisable to consider discontinuing treatment or reducing the dose.
During pregnancy and breastfeeding
The drug is contraindicated during pregnancy and breastfeeding.
In childhood
The drug is not prescribed to persons under 25 years of age.
In old age
With special care is appointed to people of advanced age. A slow increase in dosage is required.
For impaired renal function
The drug is not prescribed to patients with severe renal insufficiency.
For impaired liver function
The drug is contraindicated in severe liver dysfunction.
drug interaction
Trihexyphenidil and metoclopramide reduce the rate of absorption of levodopa, and antacids reduce the degree of absorption.
Antipsychotics, opioids and antihypertensive drugs containing reserpine contribute to the suppression of the drug. Pyridoxine reduces the antiparkinsonian effect of the drug.
It is contraindicated to combine the drug with non-selective MAO inhibitors.
The combined use of the drug with antihypertensive drugs can lead to the development of orthostatic hypotension.
It is acceptable to combine levodopa/benserazide with other antiparkinsonian drugs.
High-protein food reduces the therapeutic effect of the drug.
Levodopa/benserazide may interfere with laboratory test results for creatinine, bilirubin, alkali phase, uric acid, and catecholamines.
Terms of dispensing from pharmacies
Released by prescription.
4.42 out of 5 (6 Votes) C 9 H 11 NO 4Pharmacological group of the substance Levodopa
Nosological classification (ICD-10)
CAS code
59-92-7Characteristics of the substance Levodopa
White crystalline powder. Slightly soluble in water, insoluble in alcohol.
Pharmacology
pharmachologic effect- antiparkinsonian.It is a precursor to dopamine. Penetrates through the BBB, accumulates in the basal ganglia and turns into dopamine, making up for the lack of the latter in the extrapyramidal system. As a result, muscle rigidity and hypokinesia decrease. Well absorbed when taken orally; C max is determined after 1-2 hours, some of it is already in the blood transformed into dopamine and does not enter the basal ganglia (dopamine does not pass the BBB). It is excreted mainly by the kidneys.
The use of the substance Levodopa
Parkinson's disease, symptomatic parkinsonism.
Contraindications
Hypersensitivity, severe atherosclerosis, hypertension, diseases of the liver, kidneys, blood, glaucoma, melanoma, bronchial asthma, mental illness, uncompensated pathology of the cardiovascular, respiratory, endocrine systems.
Application restrictions
Pregnancy, breastfeeding, children's age (up to 12 years), history of myocardial infarction.
Side effects of Levodopa
Choreoathetoid hyperkinesis, arrhythmia, psychotic and paranoid reactions, dyspepsia, gastrointestinal ulceration, headache, dizziness, visual disturbances, hemolytic anemia, agranulocytosis and leukopenia, alopecia, allergic reactions.
Interaction
The effect is weakened by vitamin B 6 . Enhances the action of MAO inhibitors.
What is Levodopa? Instructions for use, price, reviews of this medicine will be discussed a little further. You will also learn about what this medication is prescribed for, whether it has side reactions and contraindications, in what form it goes on sale, what is included in its composition, and so on.
Composition, form, description
What components does the drug "Levodopa" contain? Instructions for use indicate that the active substance of this drug is levodopa. It goes on sale in the form of white round flat-cylindrical tablets packed in contour cells and cardboard packs, respectively.
The principle of action of the drug
How does Levodopa work? Instructions for use, reviews report that this is an anti-Parkinsonian combined remedy. It is aimed at eliminating rigidity, hypokinesia, tremor, salivation and dysphagia.
Entering the body, the active ingredient of the drug is converted into dopamine (in the central nervous system), thereby making up for the lack of this element.
Dopamine, which occurs in peripheral tissues, does not show the anti-Parkinsonian effect of levodopa. This is due to the fact that it does not penetrate the central nervous system and is the main cause of adverse reactions from taking the drug.
To reduce the dose of the active substance in the human body, the drug is prescribed in combination with peripheral dopa decarboxylase inhibitors. This technique helps to reduce the side effects from taking the pills.
Pharmacokinetics
How much is Levodopa absorbed? Instructions for use states that after the drug enters the body, it is quickly absorbed from the intestine.
The absorption of the active substance is about 20-30%. In this case, the therapeutic effect is observed after about 3 hours.
Eating (including certain foods) directly affects the absorption of the drug.
The drug undergoes metabolism, resulting in the formation of several metabolites. Excretion of the active substance is carried out through the kidneys and through the intestines.
Indications for use
Under what conditions are patients prescribed the drug "Levodopa"? Instructions for use reports the following indications:
- postencephalitis syndrome, which occurs with cerebrovascular diseases or toxic intoxication;
- parkinsonism syndrome, in addition, which was caused by the use of antipsychotics;
- Parkinson's disease.
Contraindications
Are there any contraindications for Levodopa? Instructions for use informs that this medication is forbidden to be taken in the following cases:
With extreme caution, this medicine may be prescribed for:
- emphysema;
- the presence of pulmonary diseases, diseases of the heart, liver, endocrine system and blood vessels;
- bronchial asthma;
- manifestations of psychoses;
- melanoma (including history);
- angle-closure glaucoma;
- recurring seizures (convulsive);
- open-angle glaucoma, which occurs in a chronic form;
- renal and hepatic insufficiency;
- myocardial infarction (in history), as well as with manifestations of various types of arrhythmias;
- duodenal ulcer and stomach;
- manifestations of CNS depression;
- heart rhythm disorder.
The drug "Levodopa": instructions for use
The description of this medication has been presented above. How should it be taken?
According to the instructions, the drug is taken orally. The dosage is gradually increased from the minimum to the maximum (depending on the individual characteristics of the patient).
Begin treatment with a dose of 0.25-1 g. This amount is divided into three doses. The dosage is gradually increased by 0.125-0.75 g. This is done at regular intervals (for example, after three days), focusing on the patient's individual response, and until the optimal effect of therapy is observed.
The maximum dose of the drug per day should not exceed eight grams.
In no case should the medication be canceled abruptly. It is stopped gradually.
Adverse reactions
Does Levodopa cause any side effects? Instructions for use states that against the background of its administration, a person may experience some undesirable reactions that affect the work of all body systems:
- The cardiovascular system: palpitations, arrhythmia, pressure disturbance, orthostatic reactions, fainting, etc.
- Digestive tract: diarrhea, vomiting, dyspepsia, anorexia, constipation, change in taste, dry mouth, bleeding from the gastrointestinal tract.
It should also be noted that adverse reactions affecting the functioning of the hematopoietic organs, urinary, respiratory and nervous systems are not excluded. Often, while taking this medication, allergic reactions, changes in laboratory parameters and undesirable manifestations on the skin occur.
Cases of overdose (symptoms, treatment)
When using high doses of the drug, there is a significant increase in side effects. Such conditions require treatment in the form of gastric lavage, monitoring the general condition of the patient and the work of his heart. If necessary, antiarrhythmic therapy is carried out.
drug interaction
The simultaneous use of the drug in question and Ditilin, beta-adrenergic stimulants and agents that are intended for inhalation anesthesia increases the likelihood of developing heart rhythm disturbances.
The bioavailability of Levodopa can be reduced by tricyclic antidepressants.
The combination of this medication with Tioxanthen, Diazepam, antipsychotics, Phenytoin, m-anticholinergics, Clonidine, Diphenylbutylpiperidine, Papaverine, Clozapine, Phenothiazine, Pyridoxine and Reserpine quite often reduces its antiparkinsonian effect.
They increase the likelihood of hallucinations and dyskinesias, and the drug "Methyldop" enhances adverse reactions.
The combination and "Levodopa" leads to circulatory disorders. In this regard, the interval between taking such drugs should be at least 14 days.
A pronounced decrease in pressure is observed with the combination of the drug in question and Tubocurarine.
The drug "Metoclopramide" increases the bioavailability of "Levodopa", accelerating gastric emptying. This fact can negatively affect the course of the disease.
What you need to know before taking Levodopa tablets? Instructions for use (the price is indicated below) warns of a threat to health in case of abrupt withdrawal of the medication.
In cases where it is impossible to avoid dosage reduction or drug withdrawal, regular monitoring of the patient's condition is required.
In the process of therapy, it is required to constantly monitor the work of various systems, organs and blood parameters.
Price and analogues
The closest analogues of the drug "Levodopa" are such means as "Levodopa Benserazide" and "Levodopa Carbidopa". The instructions for use report that these drugs have the same indications, side effects, mechanisms of action and contraindications. The only difference between these funds is their composition.
Active substances such as benserazide and carbidopa reduce the production of dopamine in peripheral tissues, thereby increasing the amount of levodopa entering the central nervous system.
Thus, it can be safely noted that the prescription of Levodopa Carbidopa and Levodopa Benserazide (instructions for the use of these drugs is also included in the package) excludes the additional use of peripheral dopa decarboxylase inhibitors.
As for other analogues, they include drugs such as Easy Mite, Tremonorm, Dopar 275, Tidomet, Duellin, Sinemet, Zimox, Sindopa, Easycom , "On whom". Only the attending physician should prescribe them.
The price of the drug "Levodopa" is quite high. In pharmacies, you can buy this medication in the range of 1500-1850 rubles.
pharmachologic effect
The structure of levodopa is an amino acid derived from L-tyrosine. Dopamine is formed directly from levodopa with the participation of a cytoplasmic enzyme, aromatic L-amino acid decarboxylase. The end result of the influence 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 pyridoxine-dependent aromatic amino acid decarboxylase, turning into dopamine, which, however, does not penetrate the blood-brain barrier.
Carbidopa inhibits the process of decarboxylation of levodopa in peripheral tissues, while it does not penetrate 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 allows you to increase the amount of levodopa that enters the brain. When taken together, carbidopa doubles the bioavailability of levodopa. The introduction of carbidopa never leads to complete inhibition of dopa decarboxylase.
Pharmacokinetics
Levodopa
Suction
Levodopa is absorbed by active transport from the gastrointestinal tract, its passage through the blood-brain barrier is also carried out by active mechanisms. A barrier to the absorption of levodopa is the presence of dopa decarboxylase in the intestinal wall. From the stomach, levodopa is absorbed in a limited amount. The rate of gastric emptying plays a key role in drug absorption. Factors that slow down gastric emptying (food, m-anticholinergics) delay the passage of the drug into the duodenum and slow down its absorption. Cmax of the drug in the blood is observed 1-2 hours after administration.
Distribution
V d of levodopa is 0.9-1.6 l / kg. While maintaining the activity of dopa decarboxylase, the total clearance of levodopa in blood plasma is 0.5 l / kg / h. Levodopa crosses the blood-brain barrier by facilitated diffusion. The endothelium of the capillaries of the brain also contains dopa decarboxylase as the second potential barrier to the entry of levodopa into the brain, however, an insignificant part of the administered dose of levodopa is decarboxylated in these capillaries.
Metabolism
Approximately 70-75% of levodopa administered orally is metabolized in the intestinal wall (first pass effect). The liver practically does not take part in the metabolism of the first passage. With an increase in the dose of levodopa, the amount of the drug undergoing decarboxylation in the intestine decreases. Levodopa does not bind to plasma proteins. Decarboxylation of levodopa by dopa decarboxylase is the main pathway for the 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 with the formation of 3-O-methyldopa is the second pathway of levodopa metabolism. With prolonged treatment, this metabolite may accumulate. Transamination is an additional pathway for the metabolism of levodopa. The end product of this pathway is vinyl pyruvate, vinyl acetate, and 2,4,5-trihydroxyphenylacetic acid. All metabolic pathways, with the exception of transamination, are irreversible.
Selection
In combination with carbidopa, T 1/2 of levodopa increases to 3 hours. Up to 69% of levodopa can be found in the urine in humans in the form of dopamine and its metabolites - vanillinmandelic acid, norepinephrine, homovanillic acid, dihydrophenylacetic acid.
Carbidopa
At recommended doses, carbidopa does not cross the blood-brain barrier. C max in blood plasma is reached after 2-4 hours. Approximately 50% of carbidopa is excreted in the urine and feces. 35% of carbidopa excreted by the kidneys is excreted unchanged.
Indications
- Parkinson's disease and parkinsonism syndrome of known etiology (due to encephalitis, cerebrovascular disorders, intoxication with toxic substances, including carbon monoxide or manganese).
Dosing regimen
Inside, with a small amount of food or after eating, drinking water and not chewing. Since there is competition between aromatic amino acids and levodopa during absorption, the consumption of large amounts of proteins should be avoided during the use of the drug. The average daily dose of carbidopa required to suppress the peripheral conversion of levodopa is 70-100 mg. Exceeding 200 mg of carbidopa does not entail a further increase in the therapeutic effect. The daily dose of levodopa should not exceed 2000 mg. Initial dose - 1/2 tab. 2 times / day, if necessary, can be increased by 1/2 tab. / day. As a rule, at the beginning of replacement therapy, the daily dose should not exceed 3 tablets / day (1 tablet 3 times / day). Use at this dosage is recommended at the start of treatment for 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 tab. 8 times / day). The use of more than 6 tablets / day should be carried out with great care.
Side effect
From the side of the central nervous system: dyskinesia, incl. choreoathetosis, dystonia, with prolonged use, on-off syndrome, neuroleptic malignant syndrome, dizziness, ataxia / nausea, dystonic involuntary movements, convulsions, anorexia, sedation, drowsiness, confusion, nightmares, nervous tension, irritability, anxiety, insomnia; mental status changes, including paranoid effects and transient psychoses; hallucinations, depression with or without suicidal ideation, hypomania, increased libido, euphoria, dementia. Early symptoms such as muscle twitching and blepharospasm can serve as the basis for the decision to reduce the dose of the drug. Seizures have been reported, but no direct association with carbidopa/levodopa has been established.
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 hematopoietic system: rarely - leukopenia, anemia (including hemolytic), thrombocytopenia, agranulocytosis.
Allergic reactions: angioedema, urticaria, skin rash, skin itching, Shenlein-Genoch disease.
Change in laboratory parameters: change in the level of ALT, AST, alkaline phosphatase, LDH, urea nitrogen, bilirubin, protein-bound iodine, hyperuricemia, hypercreatinemia, positive direct Coombs test.
Other: syncopal conditions, chest pain, mydriasis, diplopia, dyspnea, darkening of the secretion of sweat glands, darkening of urine, weight gain or decrease.
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 temporarily reducing the dose without interrupting treatment. If the side effects do not regress, then the treatment is stopped gradually.
Other side effects that occurred while taking levodopa, which should be considered in the case of the use of the drug carbidopa / levodopa:
From the digestive system: dyspepsia, dry mouth, bitterness in the mouth, sialorrhea, dysphagia, bruxism, hiccups, pain and discomfort in the abdomen, constipation, flatulence, burning sensation of the tongue.
From the side of metabolism: decrease or increase in body weight, edema.
From the side of the central nervous system: weakness, fainting, fatigue, headache, asthenia, decreased mental activity, disorientation, ataxia, numbness, increased hand tremor, muscle cramps, trismus, activation of the latent Bernard-Horner syndrome, insomnia, anxiety, euphoria, psychomotor agitation, gait instability.
From the sense organs: diplopia, blurred vision, dilated pupils, oculogyric crises.
From the urinary system: urinary retention, urinary incontinence, priapism.
Others: hoarseness, malaise, flushing of the skin of the face, neck and chest, dyspnea, malignant melanoma. Decreased hemoglobin and hematocrit, hyperglycemia, leukocytosis, bacteriuria, erythrocyturia have been reported.
Laboratory indicators: drugs containing carbidopa/levodopa may cause a false positive reaction for ketone bodies in the urine if test strips are used to detect ketonuria. This reaction will not change after boiling urine samples. False-negative results can be obtained using the glucose oxidase method for determining glycosuria.
Contraindications for use
- angle-closure 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 the intake of MAO inhibitors;
- pregnancy;
- lactation;
- Hypersensitivity to the drug.
It should not be used to treat secondary parkinsonism caused by the use of antipsychotics (neuroleptics). Not recommended for patients under 18 years of age.
FROM caution the drug is taken for erosive and ulcerative lesions of the stomach and / or duodenum, epileptic seizures in history, severe diseases of the cardiovascular system (including myocardial infarction with a history of heart rhythm disturbances, heart failure), diseases of the endocrine system (including .h. diabetes mellitus), severe lung diseases (including bronchial asthma), mental disorders, as well as severe violations of the liver and kidneys.
Use during pregnancy and lactation
Contraindicated during pregnancy and lactation.
Overdose
Symptoms: first increase and then decrease in blood pressure, sinus tachycardia, heart rhythm disturbance, confusion, agitation, anorexia, insomnia, anxiety. Orthostatic hypotension may also develop. Symptoms of anorexia and insomnia may persist for several days.
Treatment: symptomatic. Gastric lavage, activated charcoal, if necessary, symptomatic treatment in a hospital. There is no specific antidote. Pyridoxine does not remove the effect of the drug. Currently, there are no data on the use of dialysis; it is necessary to monitor the activity of the heart in order to prevent the development of arrhythmias.
drug interaction
Co-administration with antihypertensive drugs requires special attention due to the risk of postural hypotension.
When combined with tricyclic antidepressants, arterial hypertension and dyskinesia may occur, and the bioavailability of levodopa also decreases.
The combined use of phenothiazines, butyrophenones and Carbidopa / Levodopa reduces the effect of the latter.
Carbidopa / Levodopa cannot be administered together with non-selective MAO inhibitors, because hypertensive crisis may develop. Treatment with MAO inhibitors should be discontinued at least 14 days before the start of the drug. An exception is selegiline (a selective MAO-B inhibitor) which can be used as an adjuvant in levodopa treatment.
May enhance the effect of sympathomimetics, and therefore, it is recommended to reduce their dose. With the simultaneous use of levodopa with 8-adrenergic stimulants, means for inhalation anesthesia, an increase in the risk of developing cardiac arrhythmias is possible.
When using amantadine with levodopa, a mutually potentiating effect is noted.
Methyldopa and levodopa can potentiate each other's side effects.
Pyridoxine is a cofactor for dopa decarboxylase, an enzyme responsible for the peripheral decarboxylation of levopa and the formation of dopamine. When it is administered to patients receiving levodopa (without dopa decarboxylase inhibitors), there is an increase in the peripheral metabolism of levodopa and a smaller amount of it penetrates the blood-brain barrier. Thus, pyridoxine reduces the therapeutic effect of levodopa, unless inhibitors of peripheral dopa decarboxylase are additionally prescribed.
With the additional appointment of dopa decarboxylase inhibitors, the daily dose of levodopa can be reduced by 70-80% while maintaining the same clinical result.
Combined use with diazepam, phenytoin, clonidine, thioxanthene derivatives, papaverine, reserpine, m-anticholinergics - a decrease in antiparkinsonian action is possible.
Terms of dispensing from pharmacies
The drug is dispensed by prescription.
Terms and conditions of storage
Store in a dry, dark place at a temperature not exceeding 25°C. Keep out of the reach of children.
Shelf life - 5 years.
Do not use after the expiry date stated on the package.
Application for violations of liver function
Carefully.
Application for violations of kidney function
Carefully.
Use in elderly patients
special instructions
It should not be used in cases of secondary parkinsonism (Parkinson's syndrome) caused by the use of antipsychotics (neuroleptics).
Treatment should be stopped gradually, because. with a sudden discontinuation of the drug, a symptom complex may develop that resembles a malignant neuroleptic syndrome (muscle rigidity, fever, increased serum CPK).
It is necessary to monitor patients who need to suddenly reduce the dose of the drug or stop taking it.
Absorption of levodopa in elderly patients is higher than in young patients. These data confirm the information about the decrease in the activity of dopa decarboxylase in tissues with age, as well as with long-term administration of levodopa.
With erosive and ulcerative lesions of the stomach and / or duodenum, epileptic seizures in history, severe diseases of the cardiovascular system (including myocardial infarction with a history of heart rhythm disturbances, 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 kidney function, the drug should be taken with caution. In such cases, patients should be closely monitored.
With prolonged treatment, it is necessary to periodically monitor the function of the liver, kidneys, the hematopoietic system and the cardiovascular system, and it is also necessary to monitor the mental status of the patient.
During surgical operations, if general anesthesia is required, the drug Carbidopa / Levodopa is prescribed without reducing the dose, as long as the patient can take drugs and liquids by mouth. When using halothane and cyclopropane, the drug is discontinued at least 8 hours before surgery. Treatment is continued after surgery at the same dose. Patients with glaucoma while taking the drug should regularly monitor intraocular pressure.
Influence on the ability to drive vehicles and control mechanisms
It is necessary to refrain from driving, as well as activities that require the speed of psychomotor reactions.
