Levodopa / Benserazid-Teva

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Levodopa / Benserazid-Teva: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Drug interactions
14. Analogs
15. Terms and conditions of storage
16. Terms of dispensing from pharmacies
17. Reviews
18. Price in pharmacies

Latin name: Levodopa / Benserazide-Teva

ATX code: N04BA02

Active ingredient: levodopa (levodopa) + benserazide (benserazide)

Manufacturer: TEVA Pharmaceutical Plant Private Co. Ltd. (TEVA Pharmaceutical Works Private Ko. Ltd.) (Hungary)

Description and photo update: 2019-20-08

Prices in pharmacies: from 1031 rubles.

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Levodopa / Benserazide-Teva is a drug used in Parkinson's disease.

Release form and composition

Levodopa / Benserazide-Teva is available in the form of tablets: pink, round, with slight marbling, on both sides - cruciform risk; 100 mg of levodopa - biconvex; 200 mg levodopa - flat, chamfered, on one side - in two sections of the cross-shaped notch engraving "B" and "L" (20, 30, 50, 60 or 100 pcs. in vials of PVP (high density polyethylene), 1 bottle in a cardboard box).

The composition of 1 tablet contains active ingredients:

Levodopa - 100 or 200 mg;
Benserazide - 25 or 50 mg (as benserazide hydrochloride - 28.5 or 57 mg).

Auxiliary components (tablets 100/200 mg, respectively): mannitol - 89.15 / 178.3 mg, pregelatinized corn starch - 18.7 / 37.4 mg, microcrystalline cellulose - 4.95 / 9.9 mg, povidone K25 - 11/22 mg, anhydrous calcium hydrogen phosphate - 7.97 / 15.94 mg, colloidal silicon dioxide - 0.71 / 1.42 mg, crospovidone (type A) - 8.25 / 16.5 mg, dye iron oxide red (E172) 0.27 / 0.54 mg, magnesium stearate 5.5 / 11 mg.

Pharmacological properties

Pharmacodynamics

The anti-Parkinsonian drug is a combination of two active components: the dopamine precursor, levodopa, and the peripheral decarboxylase inhibitor of aromatic L-amino acids, benserazide.

In patients with Parkinson's disease, the neurotransmitter dopamine is produced in insufficient quantities in the basal nuclei. When using levodopa, a nutrient that is a direct metabolic precursor of dopamine, replacement therapy occurs. Since a large proportion of the taken levodopa is converted into dopamine in the interstitial tissues of the intestine, liver, kidneys, heart, stomach, peripheral dopamine formed in this way does not take part in the antiparkinsonian action of levodopa, since it penetrates the BBB (blood-brain barrier) poorly, except Moreover, he is responsible for most of its unwanted effects.

To improve the action of levodopa, it is highly desirable to block its extracerebral decarboxylation. Due to the simultaneous administration of a peripheral decarboxylase inhibitor of aromatic L-amino acids benserazide, which reduces the formation of dopamine in peripheral tissues, simultaneously with levodopa, the amount of levodopa entering the central nervous system (central nervous system) indirectly increases, and secondly, the manifestation of undesirable reactions of levodopa decreases. The combination of levodopa and benserazide in a 4: 1 ratio has the same effect as monotherapy with high doses of levodopa.

Pharmacokinetics

absorption: levodopa and benserazide are absorbed mainly in the upper part of the small intestine. The maximum concentration (Cmax) in plasma after oral administration of the drug is reached after about 1 hour. The values of the area under the concentration-time curve (AUC) and Cmax vary in direct proportion to the dose taken. Absorption also depends on the intragastric pH and the rate of evacuation of gastric contents. The presence of food in the stomach slows down absorption. Taking the drug after meals reduces Cmax in plasma by 30% and increases the time to reach it. The absorption rate is reduced by 15%. The drug is found in large quantities in the small intestine, kidneys and liver, only about 1-3% penetrates into the brain. The half-life (T _1/2) of the drug is approximately 3 hours;
distribution: levodopa - penetrates the BBB through a saturable transport system, does not bind to plasma proteins, Vd (volume of distribution) is 57 l, AUC in cerebrospinal fluid is 12% of the plasma index; benserazide - does not penetrate the BBB, accumulates mainly in the small intestine, kidneys, lungs, and liver, penetrates the placental barrier;
metabolism: levodopa - metabolized mainly by two main pathways (o-methylation and decarboxylation) and two additional (oxidation and transamination). Aromatic L-amino acid decarboxylase converts levodopa to dopamine. At the end of this path, the main metabolic products are formed - dihydroxyphenylacetic and homovanillic acids. 3-o-methyldopa is formed from levodopa when it is methylated by catechol-o-methyl transferase. This main metabolite has T _1/2is equal to 15 hours, as a result of which patients who received therapeutic doses of the drug cumulate it. The use of levodopa with benserazide leads to a decrease in its peripheral decarboxylation, an increase in plasma concentrations of levodopa and 3-o-methyldopa, a decrease in the level of catecholamines (dopamine and norepinephrine), and a decrease in the concentration of phenol carboxylic acids (homovanillic and dihydrophenylacetic). Benserazide undergoes hydroxylation in the liver and intestinal mucosa to form trihydroxybenzylhydrazine, a metabolite that is a potent inhibitor of aromatic L-amino acid decarboxylase;
excretion: T _{1/2 of} levodopa against the background of peripheral inhibition of aromatic L-amino acid decarboxylase is 1.5 h, its plasma clearance is 430 ml / min; Benserazide is eliminated by metabolism almost completely, its metabolites are mainly excreted by the kidneys - up to 64%, to a lesser extent by the intestines - up to 24%. The absolute cumulation of the drug averages 98% (range 74–112%).

Since less than 10% of unchanged levodopa / benserazide is excreted by the kidneys, dose adjustment is not required for mild to moderate renal failure.

In old age (65–78 years) in patients with Parkinson's disease, the T _1/2 and AUC of levodopa increase by 25%, these changes are not clinically significant.

Indications for use

According to the instructions, Levodopa / Benserazide-Teva is prescribed for the treatment of Parkinson's disease.

Contraindications

Severe functional disorders of the organs of the endocrine system, liver, kidneys;
Exogenous and endogenous psychoses;
Glaucoma;
Dysfunctions of the cardiovascular system in severe forms;
Combination therapy with non-selective monoamine oxidase inhibitors, combination of monoamine oxidase inhibitors type A and B;
Pregnancy and the period of breastfeeding;
Age under 25;
Childbearing age in women (without the use of reliable contraceptive methods);
Hypersensitivity to drug components.

Instructions for the use of Levodopa / Benserazid-Teva: method and dosage

Levodopa / Benserazid-Teva tablets are taken orally, observing the intervals with meals (preferably at least 30 minutes before or 1 hour after).

Therapy begins with small doses, increasing them gradually (individually for each patient) until a therapeutic effect is achieved. High doses for simultaneous administration of the drug should be avoided.

If levodopa is prescribed for the first time, the initial single dose is 50 mg levodopa / 12.5 mg benserazide, the frequency of administration is 2-4 times a day. With good tolerance, the dose is increased by 50-100 mg of levodopa once every 3 days until a therapeutic effect is achieved.

In the future, the dose is selected once a month. The therapeutic effect, as a rule, is noted already when taking 200-400 mg of levodopa / 50-100 mg of benserazide per day (maximum - 800 mg of levodopa / 200 mg of benserazide).

The daily dose should be divided into 4 or more doses (to ensure optimal therapeutic effect). With the development of side effects, you need to reduce the daily dose or stop increasing the dose.

Achievement of optimal therapeutic effect usually occurs when taking 300-800 mg levodopa / 100-200 mg benserazide.

For patients who have previously taken levodopa, the use of Levodopa / Benserazide-Teva should be started 12 hours after stopping the administration of levodopa. The dose is prescribed in the amount of about 20% of the previous dose of levodopa, which allows you to maintain the previously achieved therapeutic effect. In the future, if necessary, the dose is increased according to the scheme described for patients who have not previously taken levodopa.

Patients who have previously taken a combination of levodopa with an aromatic L-amino acid decarboxylase inhibitor, the use of the drug Levodopa / Benserazide-Teva should be started 12 hours after stopping taking such a drug. To minimize the decrease in the already achieved therapeutic efficacy, the previous therapy should be interrupted at night, Levodopa / Benserazid-Teva tablets should be taken from the next morning. In the future, if necessary, the dose is increased according to the scheme described for patients who have not previously taken levodopa.

Levodopa / Benserazide-Teva may be prescribed for patients who have previously taken other antiparkinsonian drugs. When an obvious therapeutic effect is achieved, it is possible to revise the therapy regimen with a decrease or withdrawal of an alternative drug.

In case of strong motor fluctuations, it is recommended to increase the frequency of taking the drug without changing the daily dose. In elderly patients, the dose is increased more slowly. The experience of therapy in children and adolescents is limited.

No dose adjustment is required for moderate and mild hepatic and renal failure.

The dose should be reduced if spontaneous movements such as athetosis or chorea appear in the later stages of therapy.

With prolonged treatment episodes of "freezing", the phenomenon of "on-off" and weakening of the effect by the end of the dose duration can be significantly reduced or eliminated by lowering the dose or more frequent use of the drug at a lower dose. To enhance the effect of treatment, you can increase the dose in the future.

With the development of side effects from the cardiovascular system, the dose must be reduced.

Side effects

During therapy with different frequencies, disorders from various body systems can develop (very often - not less than 10%; often - not less than 1% and less than 10%; sometimes - not less than 0.1% and less than 1%; rarely - not less than 0.01% and less than 0.1%; very rarely - less than 0.01%, taking into account single messages):

Cardiovascular system: very rarely - arrhythmias, increased blood pressure, orthostatic hypotension (usually weakened after lowering the dose); with an unknown frequency - "hot flashes";
Hematopoietic system: very rarely - transient leukopenia, hemolytic anemia, thrombocytopenia;
Gastrointestinal tract: very rarely - dryness of the oral mucosa, nausea, diarrhea, vomiting, isolated cases of change or loss of taste; with an unknown frequency - gastrointestinal bleeding;
Nervous system: often - convulsions, increased manifestations of the syndrome of "restless legs", dizziness, headache, episodes of "freezing", spontaneous movement disorders (such as athetosis and chorea), weakening of the effect by the end of the dose, the phenomenon of "on-off"; very rarely - episodes of sudden drowsiness, severe drowsiness;
Subcutaneous tissue and skin: rarely - rash, itching of the skin;
Laboratory indicators: infrequently - an increase in creatinine and urea in the blood, bilirubin concentration, a transient increase in the activity of "hepatic" transaminases, alkaline phosphatase, a change in the color of urine to red, when standing - darkening;
Mind: rarely - moderate delight, increased libido, agitation, insomnia, depressed mood, anxiety, anorexia, delirium, depression, aggression, pathological hypersexuality, gambling tendency; very rarely - short-term disorientation, hallucinations;
Others: with an unknown frequency - increased sweating, febrile fever.

Overdose

Symptoms of an overdose of Levodopa / Benserazide-Teva are an increase in such undesirable reactions as nausea and vomiting, arrhythmia, insomnia, confusion, pathological involuntary movements. Since the absorption of the drug from the gastrointestinal tract occurs slowly, the development of overdose symptoms may be delayed.

Gastric lavage should be performed and with the help of enterosorbents (Polysorb, Smecta, Activated carbon) to prevent further absorption of the drug in the gastrointestinal tract. In addition, symptomatic therapy is recommended: the use of respiratory analeptics, antiarrhythmic drugs, antipsychotics; control of vital functions.

special instructions

Side effects from the digestive system, which occur most often in the initial stages of therapy, are largely eliminated by taking Levodopa / Benserazide-Teva tablets with a small amount of liquid or eating, as well as with a slower increase in the dose. The use of the drug for the treatment of Huntington's chorea and iatrogenic extrapyramidal syndrome is not recommended.

In the presence of anamnestic data on gastrointestinal ulcers, osteomalacia and seizures, the corresponding indicators should be regularly monitored. In the course of therapy, it is necessary to monitor the indicators of kidney, liver function and blood counts. Patients with ischemic heart disease, myocardial infarction, a history of heart rhythm disturbances should be monitored regularly for the electrocardiogram.

Patients with a history of orthostatic hypotension should be under medical supervision, especially at the beginning of therapy.

In diabetes mellitus, it is necessary to frequently monitor the concentration of glucose in the blood and adjust the dose of oral hypoglycemic drugs. During therapy, cases of sudden onset of sleep have been reported, which should be taken into account by patients.

The use of the drug Levodopa / Benserazide-Teva increases the likelihood of malignant melanoma (patients with malignant melanoma, including a history, the drug is not recommended) and compulsive disorders.

Before carrying out general anesthesia, therapy should be carried out as long as possible, with the exception of halothane anesthesia (due to the likelihood of arterial pressure fluctuations and arrhythmias, treatment should be canceled 12-24 hours before surgery). After surgery, treatment is resumed with a gradual increase in dose.

It is impossible to abruptly stop therapy, as this can lead to a "withdrawal syndrome" (in the form of an increase in body temperature, muscle stiffness, as well as possible mental changes and an increase in serum creatinine phosphokinase activity) or akinetic crises (in some cases, in life-threatening forms) … When such symptoms appear, the patient should be under medical supervision (if necessary, hospitalization is possible) with appropriate therapy, which may include re-appointment of the drug Levodopa / Benserazide-Teva.

Depression can be a clinical manifestation of the underlying disease (parkinsonism) or develop during drug use. For the timely detection of unwanted mental reactions, the condition of such patients should be monitored.

In some cases, the emergence of cognitive and behavioral disorders associated with the uncontrolled use of increasing doses of the drug and a significant increase in therapeutic doses is noted.

Influence on the ability to drive vehicles and complex mechanisms

If you develop excessive daytime sleepiness or sudden episodes of sleep during therapy, you should refuse to drive or work with equipment. If these symptoms occur, consider reducing the dose or discontinuing the drug.

Application during pregnancy and lactation

In pregnancy and women of reproductive age who do not use reliable contraception, the drug is contraindicated. If pregnancy is suspected, Levodopa / Benserazid-Teva should be canceled immediately.

If drug therapy is required during lactation, breastfeeding should be interrupted, since there is a risk of impaired skeletal formation in the child.

Pediatric use

There is no sufficient experience with the use of Levodopa / Benserazide-Teva in children, adolescents and young people under the age of 25, and therefore the use of the drug in this age category of patients is contraindicated.

With impaired renal function

The drug is contraindicated in patients with severe renal impairment. With mild to moderate renal failure, dose adjustment is not necessary.

For violations of liver function

The drug is contraindicated in patients with severe liver dysfunction. With mild to moderate hepatic impairment, dose adjustment is not necessary.

Drug interactions

When the drug Levodopa / Benserazide-Teva is co-administered with certain drugs, the following effects may occur:

Trihexyphenidil (m-anticholinergics): a decrease in the rate (but not degree) of absorption of levodopa;
Ferrous sulfate: decrease in C _max (maximum concentration of a substance in the blood) and AUC (total concentration of a substance in blood plasma) of levodopa;
Antacids: decrease in the degree of absorption of levodopa / benserazide;
Non-selective monoamine oxidase inhibitors, a combination of type A and B selective monoamine oxidase inhibitors: development of a hypertensive crisis (the combination is contraindicated, a break of at least 14 days must be observed);
Metoclopramide: increasing the rate of absorption of levodopa;
Opioids, antipsychotics, antihypertensive drugs containing reserpine: suppression of the action of levodopa / benserazide (you must use the lowest doses of these drugs);
Pyridoxine: a decrease in the antiparkinsonian effect of levodopa / benserazide;
Selective monoamine oxidase inhibitors of type A and B (rasagiline, selegiline, moclobemide): an increase in the effect of levodopa / benserazide, no dangerous interaction was detected;
Antihypertensive drugs: development of orthostatic hypotension;
Sympathomimetics (amphetamine, norepinephrine, epinephrine, isoproterenol): potentiation of their action (the combination is not recommended, if simultaneous use is necessary, the state of the cardiovascular system should be carefully monitored, the dose of sympathomimetics should be reduced if necessary);
Other antiparkinsonian drugs (anticholinergic drugs, dopamine receptor agonists, amantadine): increased therapeutic and undesirable effects (dose adjustment of levodopa / benserazide or other drug may be required);
Catechol-O-methyltransferase inhibitor: control needed, levodopa / benserazide dose adjustment may be required;
Halothane anesthesia: the development of arrhythmias and fluctuations in blood pressure (therapy with Levodopa / Benserazide-Teva should be canceled 12-48 hours before the operation);
Protein-rich food: reducing the therapeutic effect of the drug.

Levodopa / Benserazide-Teva may affect the results of laboratory studies of creatinine, catecholamines, glucose, uric acid, bilirubin, alkaline phosphatase. It is possible to determine an increase in the concentration of creatinine and urea in the blood, a false-positive result of the Coombs test, a false-negative reaction to glucose in urine when it is determined using the glucose oxidase glucose method.

Analogs

Analogs of Levodopa / Benserazid-Teva are: Dopar 275, Duellin, Zimox, Izikom, Carbidopa / Levodopa, Nakom, Madopar 250, Madopar 125, Sindopa, Sinemet, Tidomet, Tremonorm.

Terms and conditions of storage

Store in a dry place out of reach of children at temperatures up to 25 ° C.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Levodopa / Benserazid-Teva

In the treatment of Parkinson's disease, according to reviews, Levodopa / Benserazide-Teva acts differently on all patients. Sometimes, with prolonged use, even under medical supervision, patients exhibit increased irritability and bouts of aggression, and often hallucinations. In some patients, dose reduction relieves symptoms of mental disorders without impairing motor function. At the same time, in other patients, a decrease in the daily dose or cessation of drug therapy can not only preserve the existing mental disorders, but can also worsen motor function. Therefore, experts recommend at the beginning of taking the drug to expect possible severe side effects and be patient to select the optimal dose. Treatment is recommended to be carried out exclusively under the supervision of a physician,which will take into account the slightest changes on the part of the psyche or the cardiovascular system in the patient's condition and respond to them in a timely manner.

Price for Levodopa / Benserazid-Teva in pharmacies

Average prices for Levodopa / Benserazid-Teva for 100 tablets in a package: 100 mg + 25 mg - 615 rubles; 200 mg + 50 mg - 1154 R.