Levodopa use and its effect on the body. Use in children
P N013777/01-090608Tradename: Carbidopa/Levodopa
MNI or group name: Levodopa+Carbidopa
Dosage form:
pillsCompound
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
The tablets are oval, biconvex, light blue in color, with lighter or darker inclusions, with a score line on one side and the manufacturer’s logo on the other side.
Pharmacotherapeutic group:
antiparkinsonian drug (dopamine precursor + peripheral decarboxylase inhibitor)
CodeATX: Pharmacological properties
Pharmacodynamics
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 - 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, but 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 entering the brain. When taken orally together, carbidopa doubles the bioavailability of levodopa. Administration of carbidopa never leads to complete inhibition of dopadecarboxylase.
Pharmacokinetics
a./Levodopa
ABSORPTION: 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 dopadecarboxylase in the intestinal wall. Levodopa is absorbed from the stomach in limited quantities. The rate of gastric emptying plays a key role in drug absorption. Factors that slow down gastric emptying (food, anticholinergic drugs) 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 dopadecarboxylase activity is maintained, the total plasma clearance of levodopa is 0.5 l/kg/hour. Levodopa penetrates the blood-brain barrier by facilitated diffusion. The endothelium of brain capillaries also contains dopadecarboxylase as a second potential barrier to the entry of levodopa into the brain, however, a small portion is decarboxylated in these capillaries.
METABOLISM: Approximately 70-75% of orally administered levodopa is metabolized in the intestinal wall (first-pass effect). The liver practically does not take part in first-pass metabolism. As the dose of levodopa increases, the amount of the drug undergoing decarboxylation in the intestine decreases. Levodopa does not bind to plasma proteins. Decarboxylation of levodopa by dopadecarboxylase is the main pathway for the formation of dopamine from levodopa. Large amounts of this enzyme are found in the intestines, liver and kidneys. Methoxylation of levodopa by catechol-O-methyltransferase to form 3-O-methyldopa is the second pathway of levodopa metabolism. With long-term treatment, this metabolite may accumulate. Transamination is an additional pathway for the metabolism of levodopa. The end products of this pathway are vinyl pyruvate, vinyl acetate, and 2,4,5-trihydroxyphenylacetic acid. All metabolic pathways, with the exception of transamination, are irreversible.
Elimination: In combination with carbidopa, the 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 penetrate the blood-brain barrier. The maximum concentration in blood plasma is achieved 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
Should not be used to treat secondary parkinsonism caused by the use of antipsychotics (neuroleptics). It is not recommended for use in 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, a history of epileptic seizures, severe diseases of the cardiovascular system (including myocardial infarction with a history of cardiac arrhythmias, heart failure), diseases of the endocrine system ( including diabetes), severe lung diseases (including bronchial asthma), mental disorders, as well as severe impairment of liver and kidney function. Directions for use and doses
Inside, with a small amount of food or after a meal, with water and without chewing. Since there is competition between aromatic amino acids and levodopa for absorption, large amounts of protein should be avoided while using 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, it can be increased by 1/2 tablet per 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 beginning of treatment of severe cases of parkinsonism. As an exception, the daily dose of the drug can be increased during monotherapy, but should not exceed 8 tablets (1 tablet 8 times a day). Use of more than 6 tablets per day should be done 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, increased excitability, anxiety, insomnia; changes in mental status, including paranoid effects and transient psychoses; hallucinations, depression with or without the development of suicidal intentions, hypomania, increased libido, euphoria, dementia. The basis for the decision to reduce the dose of the drug may be early symptoms such as muscle twitching and blepharospasm. Convulsions have been reported, but a direct relationship with carbidopa/levodopa has not 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, Henoch-Schönlein disease.
Changes in laboratory parameters: changes in the level of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, urea nitrogen, bilirubin, protein-bound iodine, hyperuricemia, hypercreatinemia, positive direct Coombs test.
Other: syncope, chest pain, mydriasis, diplopia, dyspnea, darkening of sweat gland secretions, darkening of urine, weight gain or loss.
Side effects usually 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 interruption in treatment. If side effects do not regress, then treatment is stopped gradually. Other side effects that have occurred while taking LEVODOPA, which should be taken into account when using the drug carbidopa/levodopa:
Gastrointestinal tract: dyspepsia, dry mouth, feeling of bitterness in the mouth, sialorrhea, dysphagia, bruxism, attacks of hiccups, pain and discomfort in the abdomen, constipation, flatulence, burning sensation of the tongue.
Metabolism: loss or increase in body weight, edema.
CNS: Weakness, fainting, fatigue, headache, asthenia, decreased mental activity, disorientation, ataxia, stupor, increased hand tremors, muscle cramps, trismus, activation of latent Bernard-Horner syndrome, insomnia, anxiety, euphoria, psychomotor agitation, instability gait Sense organs: diplopia, blurred vision, dilated pupils, oculogyric crises.
Genitourinary system: urinary retention, urinary incontinence, priapism.
Other side effects: hoarseness, malaise, “flushes” of blood to the skin of the face, neck and chest, dyspnea, malignant melanoma. A decrease in hemoglobin and hematocrit, hyperglycemia, leukocytosis, bacteriuria, and erythrocyturia have been reported.
Changes in laboratory values: Products containing carbidopa-levodopa may cause a false-positive reaction for ketone bodies in urine when test strips are used to determine ketonuria. This reaction will not change after boiling urine samples. False-negative results can be obtained when using the glucose oxidase method for determining glycosuria. Overdose
Symptoms: first an increase and then a decrease in blood pressure, sinus tachycardia, cardiac arrhythmias, confusion, agitation, anorexia, insomnia, anxiety. Orthostatic hypotension may also develop. Symptoms of anorexia and insomnia may persist for several days.
Treatment: symptomatic. Gastric lavage, intake of activated carbon, and, if necessary, symptomatic treatment in a hospital setting. There is no specific antidote. Pyridoxine does not reverse the effect of the drug. There is currently no data on the use of dialysis. It is necessary to monitor cardiac activity in order to prevent the development of arrhythmias. Interaction with other drugs
Should not be used in cases of secondary parkinsonism (Parkinson's syndrome) caused by the use of antipsychotics (neuroleptics).
Treatment should be discontinued gradually, since sudden discontinuation of the drug may result in the development of a symptom complex reminiscent of neuroleptic malignant syndrome (muscle rigidity, increased body temperature, increased CPK levels in the blood serum). Monitoring of patients who need to suddenly reduce the dose of the drug or interrupt its use is necessary. The absorption of levodopa in elderly patients is higher than in young ones. These data confirm the information about a decrease in dopadecarboxylase activity in tissues with age, as well as with long-term administration of levodopa.
For erosive and ulcerative lesions of the stomach and/or duodenum, a history of epileptic seizures, severe diseases of the cardiovascular system (including myocardial infarction with a history of cardiac arrhythmias, heart failure), diseases of the endocrine system (including diabetes), severe lung diseases (including bronchial asthma), mental disorders, as well as severe liver and kidney dysfunction, the drug should be taken with caution. In such cases, patients should be closely monitored.
With long-term treatment, it is necessary to periodically monitor the function of the liver, kidneys, hematopoiesis and cardiovascular systems, and monitoring the patient's mental status is also necessary.
During surgical operations, if general anesthesia is required, the drug Carbidopa/Levodopa is prescribed without reducing the dose until the patient can take medications and liquids orally. 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 vehicles:
it is necessary to refrain from driving vehicles, as well as activities that require rapid psychomotor reactions. Release form
Tablets 25 mg+250 mg
10 tablets in a blister made of PVC film and aluminum foil. 10 blisters along with instructions for use are placed in a cardboard box. Storage conditions
In a dry place, protected from light, at a temperature not exceeding 25 ° C.
Keep out of the reach of children. Best before date
5 years.
Do not use after the expiration date stated on the packaging. Conditions for dispensing from pharmacies
On prescription.
Manufacturer:
Pharmaceutical plant "Remedica Ltd", Cyprus. /Manufacturers of pharmaceuticals "Remedica Ltd", Cyprus/.
For product quality complaints please contact:
JSC "Pharmimex" Russian Federation, Moscow, st. Bolshaya Dimitrovka, no. 7/5, building 5;
Photo of the drug
Latin name: Levodopa/Benserazide-Teva
ATX code: N04BA
Active substance: Levodopa + Benserazide
Manufacturer: Pharmaceutical plant Teva Private Co. Ltd., Hungary
Description is valid on: 14.12.17
Levodopa benserazide is an antiparkinsonian drug.
Active substance
Levodopa + Benserazide.
Release form and composition
Levodopa benserazide is sold in tablet form. The medication is available in polyethylene bottles (20, 30, 50, 60 or 100 tablets), placed in cardboard packages of 1 pc.
Indications for use
The indication for prescribing the drug 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 who are not using reliable methods of contraception.
- Severe functional impairment of the cardiovascular system.
- The period of pregnancy and breastfeeding.
- Combined use 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. The tablets should be taken half an hour before or an 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 the therapy, it is possible to increase the dosage of the drug to 100 mg levodopa/25 mg benserazide, which are taken every three days until the desired effect is achieved.
The maximum permissible dosage per day is 800 mg for levodopa and 200 mg for benserazide.
If an adverse reaction develops, it is necessary to reduce the dosage of the drug or completely discontinue this drug.
For patients who have previously taken levodopa, this drug should be started 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 begin 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.
Dosage regimens in special cases
Patients experiencing severe motor fluctuations should take the drug more than 4 times a day, following the daily dosage.
Elderly people should increase their dosage very slowly.
Patients with mild to moderate renal and hepatic impairment do not require dose adjustment.
In case of spontaneous movements (athetosis or chorea) or a negative reaction from the cardiovascular system, it is recommended to reduce the daily dosage.
Side effects
Using the drug may cause the following side effects:
- Central nervous system: often - episodes of “freezing”, headache, “on-off” phenomenon, dizziness, weakening of the effect towards 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 reducing the dose of the drug), arrhythmias; frequency unknown – “tides”.
- Hematopoietic system: sometimes – thrombocytopenia, transient leukopenia, hemolytic anemia.
- Digestive system: sometimes - attacks of nausea, diarrhea, vomiting, dryness of the oral mucosa, isolated cases of changes or loss of taste; 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 addiction to gambling, moderate delight, depression, aggression; sometimes – temporary disorientation, hallucinations.
- Laboratory indicators: uncommon - increased concentrations of bilirubin, alkaline phosphatase, creatinine and urea in the blood, transient increase in the activity of liver enzymes, change in urine color to red (may darken when standing).
- Other: frequency unknown - excessive sweating, febrile fever.
Overdose
Symptoms of overdose: 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.
Symptomatic therapy is used as treatment, which consists of taking antipsychotics, antiarrhythmic drugs and respiratory analeptics.
Analogs
Analogs by ATC code: Levodopa + Benserazide, Madopar.
Do not decide to change the drug on your own; consult your doctor.
pharmachologic effect
Levodopa Benserazide is a combination drug that has an antiparkinsonian effect. It contains a dopamine precursor and a peripheral aromatic L-amino acid decarboxylase inhibitor.
In Parkinson's disease, dopamine is synthesized in insufficient quantities and this drug is used as replacement therapy. The main part of levodopa is transformed into dopamine in peripheral tissues, which does not have an antiparkinsonian effect. To increase the effect of this substance, the drug is supplemented with benserazide.
special instructions
Undesirable manifestations from the gastrointestinal tract (occur at the initial stage of therapy) are largely eliminated with a slower dose increase, as well as if the tablets are taken with a small amount of liquid or taken with meals. The use of the drug for the treatment of Huntington's chorea and iatrogenic extrapyramidal syndrome is not advisable.
People with a history of osteomalacia, gastrointestinal ulcers and seizures need to regularly analyze the relevant indicators. During therapy, it is necessary to monitor the functional parameters of the kidneys, liver, and blood count. Patients with a history of heart rhythm disturbances, myocardial infarction, or coronary heart disease should undergo regular electrocardiogram monitoring.
Patients with a history of orthostatic hypotension should be closely monitored by a specialist, especially at the beginning of treatment.
Patients with diabetes need frequent dosage adjustments of oral hypoglycemic agents and monitoring of blood glucose levels. Cases of sudden onset of sleep have been reported with the use of Levodopa Benserazide. 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 of it) is not advisable. Use of this drug, especially in high doses, increases the likelihood of developing compulsive disorders.
Taking Levodopa Benserazide should not be stopped abruptly. This can provoke a “withdrawal syndrome” (muscle stiffness, increased body temperature, 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 close supervision of a specialist (hospitalization if necessary) and receive appropriate treatment. Sometimes repeated use of Levodopa Benserazide is advisable.
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 blood pressure fluctuations 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).
Depression may occur during treatment with Levodopa Benserazide. It can also be a clinical symptom of an underlying disease (parkinsonism). Such people should be under the supervision of a physician for timely detection of psychiatric adverse reactions.
Experience with the drug in people under 25 years of age is limited.
Patients who experience sudden sleep episodes or excessive daytime sleepiness should avoid 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
It is prescribed with special caution to elderly people. A slow increase in dosage is required.
For impaired renal function
The drug is not prescribed to patients with severe renal failure.
For liver dysfunction
The drug is contraindicated in severe liver dysfunction.
Drug interactions
Trihexyphenidyl and Metoclopramide reduce the rate of absorption of levodopa, and antacids reduce the degree of absorption.
Antipsychotics, opioids, and antihypertensive drugs containing reserpine help suppress the effect of the drug. Pyridoxine reduces the antiparkinsonian effect of the drug.
Combining the drug with non-selective MAO inhibitors is contraindicated.
Combined use of the drug with antihypertensive drugs can lead to the development of orthostatic hypotension.
Combining levodopa/benserazide with other antiparkinsonian drugs is acceptable.
High-protein foods reduce the therapeutic effect of the drug.
Levodopa/benserazide may affect laboratory test results for creatinine, bilirubin, alkaline phase, uric acid, and catecholamines.
Conditions for dispensing from pharmacies
Dispensed by prescription.
4.42 out of 5 (6 Votes) C9H11NO4Pharmacological 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 is converted into dopamine, replenishing 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 transformed into dopamine in the blood and does not enter the basal ganglia (dopamine does not pass the BBB). It is excreted mainly by the kidneys.
Use of Levodopa
Parkinson's disease, symptomatic parkinsonism.
Contraindications
Hypersensitivity, severe atherosclerosis, hypertension, liver, kidney, blood diseases, glaucoma, melanoma, bronchial asthma, mental illness, uncompensated pathology of the cardiovascular, respiratory, endocrine systems.
Restrictions on use
Pregnancy, breastfeeding, childhood (up to 12 years), history of myocardial infarction.
Side effects of Levodopa
Choreoathetoid hyperkinesis, arrhythmia, psychotic and paranoid reactions, dyspeptic symptoms, gastrointestinal ulceration, headache, dizziness, visual impairment, hemolytic anemia, agranulocytosis and leukopenia, alopecia, allergic reactions.
Interaction
The effect is weakened by vitamin B 6. Enhances the effect of MAO inhibitors.
What is the drug "Levodopa"? Instructions for use, price, reviews about this medicine will be discussed a little further. You will also learn about why this medication is prescribed, whether it has side effects and contraindications, in what form it is sold, what is included in its composition, and so on.
Composition, form, description
What components does Levodopa contain? Instructions for use indicate that the active substance of this medicine is levodopa. It goes on sale in the form of round flat-cylindrical white tablets, packaged in contour cells and cardboard packs, respectively.
The principle of action of the medication
How does Levodopa work? Instructions for use, reviews report that this is an antiparkinsonian combination drug. It is aimed at eliminating rigidity, hypokinesia, tremor, drooling and dysphagia.
Entering the body, the active component of the drug is converted into dopamine (in the central nervous system), thereby replenishing the lack of this element.
Dopamine arising in peripheral tissues does not exhibit the antiparkinsonian effects 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 medication is prescribed in combination with peripheral dopa decarboxylase inhibitors. This technique helps reduce side effects from taking pills.
Pharmacokinetics
How much Levodopa is absorbed? The instructions for use state that after the drug enters the body, it is quite quickly absorbed from the intestines.
Absorption of the active substance is about 20-30%. In this case, the therapeutic effect is observed after approximately 3 hours.
Eating (including certain foods) directly affects the absorption of the medicine.
The drug is metabolized, resulting in the formation of several metabolites. The active substance is excreted through the kidneys and intestines.
Indications for use
For what conditions are patients prescribed Levodopa? Instructions for use report the following indications:
- postencephalitic syndrome, which occurs due to cerebrovascular diseases or toxic intoxication;
- parkinsonism syndrome, except that which was caused by the use of antipsychotic drugs;
- Parkinson's disease.
Contraindications
Are there any contraindications for the drug Levodopa? The instructions for use indicate that this medication should not 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 psychosis;
- melanoma (including history);
- angle-closure glaucoma;
- repeated seizures (convulsive);
- open-angle glaucoma, which occurs in a chronic form;
- renal and liver failure;
- myocardial infarction (history), as well as manifestations of various types of arrhythmias;
- duodenal and stomach ulcers;
- manifestations of central nervous system depression;
- heart rhythm disturbances.
Levodopa: instructions for use
The description of this medication was presented above. How should it be taken?
According to the instructions, the drug is taken orally. The dosage is gradually increased from minimum to maximum (depending on the individual characteristics of the patient).
Treatment begins 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 equal 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.
Under no circumstances should the medication be abruptly discontinued. It is stopped gradually.
Adverse reactions
Does Levodopa cause side effects? The instructions for use state that while taking it, a person may experience some undesirable reactions that affect the functioning of all body systems:
- The cardiovascular system: rapid heartbeat, arrhythmia, blood pressure disturbances, 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 cannot be 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 higher doses of the drug, a significant increase in side effects is observed. Such conditions require treatment in the form of gastric lavage, monitoring the general condition of the patient and the functioning of his heart. If necessary, antiarrhythmic therapy is carried out.
Drug interactions
The simultaneous use of the drug in question and “Ditilin”, beta-agonists and agents intended for inhalation anesthesia increases the likelihood of developing cardiac arrhythmias.
The bioavailability of Levodopa can be reduced by tricyclic antidepressants.
The combination of this medication with Thioxanthene, Diazepam, antipsychotic drugs, Phenytoin, m-cholinergic blockers, 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” increases adverse reactions.
The combination of Levodopa and Levodopa leads to circulatory disorders. In this regard, the interval between taking such medications should be at least 14 days.
A pronounced decrease in pressure is observed when the drug in question is combined with Tubocurarine.
The drug Metoclopramide increases the bioavailability of Levodopa, accelerating gastric emptying. This fact can negatively affect the course of the disease.
What do you need to know before taking Levodopa tablets? Instructions for use (price listed below) warn of health hazards if the medication is abruptly discontinued.
In cases where dosage reduction or drug discontinuation cannot be avoided, regular monitoring of the patient's condition is required.
During therapy, constant monitoring of the functioning of various systems, organs and blood parameters is required.
Price and analogues
The closest analogues of the drug "Levodopa" are such drugs as "Levodopa Benserazide" and "Levodopa Carbidopa". The instructions for use indicate that these medications have the same indications, side effects, mechanisms of action and contraindications. The only difference between these products 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, we can safely note that the prescription of the drugs “Levodopa Carbidopa” and “Levodopa Benserazide” (instructions for the use of these drugs are also included in the package) excludes the additional use of peripheral dopa decarboxylase inhibitors.
As for other analogues, these include drugs such as “Izicom Mite”, “Tremonorm”, “Dopar 275”, “Tidomet”, “Dwellin”, “Sinemet”, “Zimox”, “Sindopa”, “Izicom” , "On whom". They should only be prescribed by the attending physician.
The price of Levodopa is quite high. You can purchase this medication in pharmacies for between 1500-1850 rubles.
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 - 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, but 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 entering the brain. When taken orally together, carbidopa doubles the bioavailability of levodopa. Administration of carbidopa never leads to complete inhibition of dopadecarboxylase.
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. A barrier to the absorption of levodopa is the presence of dopadecarboxylase in the intestinal wall. Levodopa is absorbed from the stomach in limited quantities. The rate of gastric emptying plays a key role in drug absorption. Factors that slow down gastric emptying (food, m-anticholinergic drugs) 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 dopadecarboxylase activity is maintained, the total plasma clearance of levodopa is 0.5 l/kg/h. Levodopa penetrates the blood-brain barrier by facilitated diffusion. The endothelium of brain capillaries also contains dopadecarboxylase as a second potential barrier to the entry of levodopa into the brain; however, a small portion of the administered dose of levodopa is decarboxylated in these capillaries.
Metabolism
Approximately 70-75% of orally administered levodopa is metabolized in the intestinal wall (the “first pass” effect). The liver practically does not take part in first-pass metabolism. As the dose of levodopa increases, the amount of the drug undergoing decarboxylation in the intestine decreases. Levodopa does not bind to plasma proteins. Decarboxylation of levodopa by dopadecarboxylase is the main pathway for the formation of dopamine from levodopa. Large amounts of this enzyme are found in the intestines, liver and kidneys. Methoxylation of levodopa by catechol-O-methyltransferase to form 3-O-methyldopa is the second pathway of levodopa metabolism. With long-term treatment, this metabolite may accumulate. Transamination is an additional pathway for the metabolism of levodopa. The end products of this pathway are 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, T1/2 of levodopa increases 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.
Carbidopa
At recommended doses, carbidopa does not penetrate the blood-brain barrier. Cmax in blood plasma 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
- Parkinson's disease and parkinsonism syndrome of known etiology (due to encephalitis, cerebrovascular disorders, intoxication with toxic substances, including carbon monoxide or manganese).
Dosage regimen
Inside, with a small amount of food or after a meal, with water and without chewing. Since there is competition between aromatic amino acids and levodopa for absorption, large amounts of protein should be avoided while using 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/day, if necessary, can be increased by 1/2 tablet/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 beginning of treatment of severe cases of parkinsonism. The daily dose of the drug, as an exception, can be increased during monotherapy, but should not exceed 8 tablets. (1 tablet 8 times/day). Use in quantities of more than 6 tablets per day should be carried out with great caution.
Side effect
From the side of the central nervous system: dyskinesia, incl. choreoathetosis, dystonia, long-term use on-off syndrome, neuroleptic malignant 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 the development of suicidal intentions, hypomania, increased libido, euphoria, dementia. The basis for the decision to reduce the dose of the drug may be early symptoms such as muscle twitching and blepharospasm. Convulsions have been reported, but a direct relationship with carbidopa/levodopa has not been established.
anorexia, nausea, vomiting, constipation, epigastric pain, dysphagia, darkening of saliva, ulcerogenic effect in predisposed patients; rarely - gastrointestinal bleeding.
From 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, Henoch-Schönlein disease.
Changes in laboratory parameters: changes in the level of ALT, AST, alkaline phosphatase, LDH, urea nitrogen, bilirubin, protein-bound iodine, hyperuricemia, hypercreatinemia, positive direct Coombs test.
Other: syncope, chest pain, mydriasis, diplopia, dyspnea, darkening of sweat gland secretions, darkening of urine, weight gain or loss.
Side effects usually 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 interruption in treatment. If side effects do not regress, then treatment is stopped gradually.
Other side effects that have occurred while taking levodopa, which should be taken into account when using the drug carbidopa/levodopa:
From the digestive system: dyspepsia, dry mouth, feeling of bitterness in the mouth, sialorrhea, dysphagia, bruxism, attacks of hiccups, pain and discomfort in the abdomen, constipation, flatulence, burning sensation of the tongue.
From the side of metabolism: loss or increase in body weight, edema.
From the side of the central nervous system: weakness, fainting, fatigue, headache, asthenia, decreased mental activity, disorientation, ataxia, stupor, increased hand tremors, muscle cramps, trismus, activation of latent Bernard-Horner syndrome, insomnia, anxiety, euphoria, psychomotor agitation, gait instability.
From the senses: diplopia, blurred vision, dilated pupils, oculogyric crises.
From the urinary system: urinary retention, urinary incontinence, priapism.
Other: hoarseness, malaise, “flushes” of blood to the skin of the face, neck and chest, dyspnea, malignant melanoma. A decrease in hemoglobin and hematocrit, hyperglycemia, leukocytosis, bacteriuria, and erythrocyturia have been reported.
Laboratory indicators: preparations containing carbidopa/levodopa may cause a false-positive reaction for ketone bodies in urine if test strips are used to determine ketonuria. This reaction will not change after boiling urine samples. False-negative results can be obtained when using the glucose oxidase method for determining glycosuria.
Contraindications for use
— 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 use of non-selective MAO inhibitors, an interval of less than 2 weeks after the end of taking MAO inhibitors;
- pregnancy;
- lactation;
- hypersensitivity to the drug.
Should not be used to treat secondary parkinsonism caused by the use of antipsychotics (neuroleptics). It is not recommended for use in patients under 18 years of age.
WITH caution the drug is taken for erosive and ulcerative lesions of the stomach and/or duodenum, a history of epileptic seizures, severe diseases of the cardiovascular system (including myocardial infarction with a history of cardiac arrhythmias, heart failure), diseases of the endocrine system (including including diabetes), severe lung diseases (including bronchial asthma), mental disorders, as well as severe liver and kidney dysfunction.
Use during pregnancy and breastfeeding
Contraindicated during pregnancy and lactation.
Overdose
Symptoms: first an increase and then a decrease in blood pressure, sinus tachycardia, cardiac arrhythmia, confusion, agitation, anorexia, insomnia, anxiety. Orthostatic hypotension may also develop. Symptoms of anorexia and insomnia may persist for several days.
Treatment: symptomatic. Gastric lavage, intake of activated carbon, and, if necessary, symptomatic treatment in a hospital setting. There is no specific antidote. Pyridoxine does not reverse the effect of the drug. Currently, there is no data on the use of dialysis; it is necessary to monitor cardiac activity in order to prevent the development of arrhythmias.
Drug interactions
Concomitant administration with antihypertensive drugs requires special attention due to the risk of postural hypotension.
When used together 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 should not be prescribed together with non-selective MAO inhibitors, because A hypertensive crisis may develop. Treatment with MAO inhibitors should be discontinued at least 14 days before starting the drug. An exception is selegiline (a selective MAO-B inhibitor), which can be used as an adjuvant during treatment with levodopa.
It may enhance the effect of sympathomimetics, and therefore it is recommended to reduce their dose. With simultaneous use of levodopa with 8-adrenergic agonists and inhalation anesthesia agents, the risk of developing heart rhythm disturbances may increase.
When amantadine is used with levodopa, a mutually potentiating effect is observed.
Methyldopa and levodopa may potentiate each other's side effects.
Pyridoxine is a cofactor of dopadecarboxylase, the enzyme responsible for the peripheral decarboxylation of levolope and the formation of dopamine. When it is prescribed to patients receiving levodopa (without dopadecarboxylase inhibitors), there is an increase in the peripheral metabolism of levodopa and less of it penetrates the blood-brain barrier. Thus, pyridoxine reduces the therapeutic effect of levodopa unless peripheral dopadecarboxylase inhibitors are additionally prescribed.
With the additional administration of dopadecarboxylase 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 may reduce the antiparkinsonian effect.
Conditions for dispensing from pharmacies
The drug is available with a prescription.
Storage conditions and periods
Store in a dry place, protected from light, at a temperature not exceeding 25°C. Keep out of the reach of children.
Shelf life - 5 years.
Do not use after the expiration date stated on the packaging.
Use for liver dysfunction
Carefully.
Use for renal impairment
Carefully.
Use in elderly patients
special instructions
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 If you suddenly stop taking the drug, you may develop a symptom complex reminiscent of neuroleptic malignant syndrome (muscle rigidity, increased body temperature, increased CPK levels in the blood serum).
Monitoring of patients who need to suddenly reduce the dose of the drug or interrupt its use is necessary.
The absorption of levodopa in elderly patients is higher than in young ones. These data confirm the information about a decrease in dopadecarboxylase activity in tissues with age, as well as with long-term administration of levodopa.
For erosive and ulcerative lesions of the stomach and/or duodenum, a history of epileptic seizures, severe diseases of the cardiovascular system (including myocardial infarction with a history of cardiac arrhythmias, heart failure), diseases of the endocrine system (including diabetes), severe lung diseases (including bronchial asthma), mental disorders, as well as severe liver and kidney dysfunction, the drug should be taken with caution. In such cases, patients should be closely monitored.
With long-term treatment, it is necessary to periodically monitor the function of the liver, kidneys, hematopoiesis and cardiovascular systems, and monitoring the patient's mental status is also necessary.
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 the drugs and liquid orally. 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 the ability to drive vehicles and operate machinery
It is necessary to refrain from driving, as well as activities that require rapid psychomotor reactions.
