Universal reference book for medicines
Product name: LEVODOPA / BENSERAZID-TEVA (LEVODOPA / BENSERAZIDE-TEVA)

Active substance: benserazide, levodopa

Type: An antiparkinsonian drug is a combination of a dopamine precursor and a peripheral dopa decarboxylase inhibitor

Manufacturer: Teva Pharmaceutical Industries (Israel) manufactured by TEVA Pharmaceutical Works Private (Hungary)
Composition, form of production and packaging
Tablets are
pink in color with light marble, round, biconvex, with a cross-shaped risk on both sides.

1 tab.

levodopa 100 mg

benserazide hydrochloride 28.5 mg,

which corresponds to the content of benserazide 25 mg

Additives: mannitol - 89.15 mg, microcrystalline cellulose - 4.95 mg, corn pregelatinized corn starch - 18.7 mg, calcium hydrophosphate (anhydrous) - 7.97 mg, povidone K25 - 11 mg, crospovidone (type A) - 8.25 mg, silicon colloidal dioxide - 0.71 mg, ferric iron oxide red (E172) 0.27 mg, magnesium stearate 5.5 mg.

20 pcs.
- bottles of high-density polyethylene (1) - packs of cardboard.
30 pcs.
- bottles of high-density polyethylene (1) - packs of cardboard.
50 pcs.
- bottles of high-density polyethylene (1) - packs of cardboard.
60 pcs.
- bottles of high-density polyethylene (1) - packs of cardboard.
100 pieces.
- bottles of high-density polyethylene (1) - packs of cardboard.
Tablets of pink color with light marble, round, flat, with a bevel, on both sides of the tablet - cruciform risk, on one side - engraving "B" and "L" in two sections of cruciform risks.

1 tab.

levodopa 200 mg

benserazide hydrochloride 57 mg,

which corresponds to the content of benserazide 50 mg

Auxiliary substances: mannitol - 178.3 mg, microcrystalline cellulose 9.9 mg, corn pregelatinized corn starch 37.4 mg, calcium hydrophosphate (anhydrous) 15.94 mg, povidone K25 22 mg, crospovidone (type A) 16.5 mg, silicon colloidal dioxide 1.42 mg, ferric iron oxide red (E172) - 0.54 mg, magnesium stearate - 11 mg.

20 pcs.
- bottles of high-density polyethylene (1) - packs of cardboard.
30 pcs.
- bottles of high-density polyethylene (1) - packs of cardboard.
50 pcs.
- bottles of high-density polyethylene (1) - packs of cardboard.
60 pcs.
- bottles of high-density polyethylene (1) - packs of cardboard.
100 pieces.
- bottles of high-density polyethylene (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2013.

PHARMACHOLOGIC EFFECT

Levodopa / benserazide is a combined antiparkinsonian preparation containing a dopamine precursor and an inhibitor of peripheral decarboxylase of aromatic L-amino acids.
With parkinsonism, the neurotransmitter dopamine is formed in the basal nucleus in insufficient quantities. Substitution therapy is carried out using levodopa, a direct metabolic precursor of dopamine. Most levodopa is converted to dopamine in peripheral tissues (intestines, liver, kidneys, heart, stomach), which does not participate in the implementation of the antiparkinsonian effect, as peripheral dopamine poorly penetrates the blood-brain barrier (BBB), and is responsible for most of its undesirable reactions. Blocking the extracerebral decarboxylation of levodopa is highly desirable. This is achieved by the simultaneous administration of levodopa and benserazide, an inhibitor of the peripheral decarboxylase of aromatic L-amino acids, which reduces the formation of dopamine in peripheral tissues, which indirectly leads to an increase in the amount of levodopa entering the central nervous system (CNS), on the one hand, and, manifestations of undesirable reactions of levodopa - on the other. The combination of these substances in a ratio of 4: 1 has the same efficacy as levodopa in high doses.
PHARMACOKINETICS

Suction.
Levodopa and benserazide are absorbed mainly in the upper parts of the small intestine. C max at ingestion is reached after approximately 1 hour. The area under the curve "concentration-time" (AUC) and C max are in proportion to the dose. Absorption depends on the rate of evacuation of stomach contents and on the values ​​of intragastric pH. The presence of food in the stomach slows down absorption. When levodopa is used after a normal meal, the maximum concentration of levodopa in the plasma is 30% less and is reached later. The degree of absorption is reduced by 15%. In large quantities is contained in the small intestine, liver and kidneys, only about 1-3% penetrates the brain. T 1/2 3 hours.
Distribution.
Levodopa passes the BBB through a saturated transport system. It does not bind to plasma proteins. Volume distribution 57 liters. AUC of levodopa in the cerebrospinal fluid is 12% of that in plasma.
Unlike levodopa, benserazid does not penetrate the BBB.
It accumulates mainly in the kidneys, lungs, small intestine and liver and penetrates the placental barrier.Metabolism. Levodopa is metabolized mainly by two basic (decarboxylation and o-methylation) and two additional routes (transamination and oxidation), Decarboxylase of aromatic L-amino acids converts levodopa into dopamine. The main end products of this pathway are homovaniline and dihydroxyphenylacetic acid. Catechol-o-methyl transferase methylates levodopa to form 3-o-methyldopa. T 1/2 of this basic metabolite is 15 hours, and in patients receiving therapeutic doses of the drug, its accumulation takes place. Decreased peripheral decarboxylation of levodopa, if used together with benserazide, leads to higher plasma concentrations of levodopa and 3-o-methyldopa and lower concentrations of catecholamines (dopamine, norepinephrine) and phenol carboxylic acids (homovanilic acid, dihydrophenylacetic acid). In the mucous membrane of the intestine and liver, benserazide is hydroxylated to form trihydroxybenzylhydrazine. This metabolite is a potent inhibitor of decarboxylase of aromatic L-amino acids.
Excretion.
On the background of peripheral inhibition of decarboxylase of aromatic L-amino acids T 1/2 levodopa 1.5 hours Clearance of levodopa from plasma 430 ml / min. Benserazide is almost completely eliminated by metabolism. Metabolites are excreted mainly by the kidneys (64%) and to a lesser extent by the intestine (24%).
Cumulation.
Absolute cumulation of levodopa in combination with benserazide averages 98% (from 74% to 112%).
Pharmacokinetics in special groups of patients.
Less than 10% of unchanged levodopa / benserazide are excreted by the kidneys, so patients with mild to moderate renal impairment do not need dose adjustment.
In elderly patients (65-78 years) with Parkinson's disease T 1/2 and AUC, levodopa increases by 25%, which is not a clinically significant change.

INDICATIONS

- Parkinson's disease.

DOSING MODE

The drug should be taken orally, if possible, at least 30 minutes before or 1 hour after meals.

Treatment begins with a small dose, gradually increasing the dose for each patient individually, until the therapeutic effect is achieved.
It is necessary to avoid high doses for simultaneous reception of the drug. The following instructions on the dosage regimen should be considered as general recommendations.
For patients who have not previously taken levodopa, an initial dose of 50 mg of levodopa / 12.5 mg of benserazide is administered 2-4 times a day (from 100-200 mg of levodopa / 25-50 mg of benserazide per day).
With good tolerance, the dose is increased by 50-100 mg of levodopa / 12.5-25 mg of benserazide every 3 days until a therapeutic effect is achieved.
Further (after the initial) dose selection is carried out at a frequency of 1 time per month.
Usually, the therapeutic effect is noted already with the intake of 200-400 mg of levodopa / 50-100 mg of benserazide per day.
The maximum daily dose of 800 mg of levodopa / 200 mg of benserazide.

The daily dose should be divided into 4 or more receptions.
Frequency of receptions should be distributed so that to provide optimum therapeutic effect. If unwanted reactions occur, either stop increasing the dose or reduce the daily dose.
The optimal therapeutic effect is achieved, as a rule, with the intake of 300-800 mg of levodopa / 100-200 mg of benserazide.

Patients who had previously taken levodopa should take Levodopa / Benserazid-Teva 12 hours after stopping Levodopa.
The dose of the drug should be approximately 20% of the previous dose of levodopa in order to maintain the therapeutic effect that has already been achieved. If necessary, the dose increases according to the scheme described for patients who did not previously take levodopa.
Patients who previously took levodopa in combination with an aromatic L-amino acid decarboxylase inhibitor should take Levodopa / Benserazid-Teva 12 hours after discontinuation of levodopa in combination with an aromatic L-amino acid decarboxylase inhibitor.
In order to minimize the reduction in the therapeutic efficacy already achieved, it is necessary to stop the previous therapy at night and start taking Levodopa / Benserazid-Teva the next morning. If necessary, the dose increases according to the scheme described for patients who did not previously take levodopa.
Patients who previously took other antiparkinsonian drugs, taking Levodopa / Benserazid-Teva is possible.
As soon as the therapeutic effect of Levodopa / Benserazid-Teva becomes evident, it is necessary to revise the treatment regimen and reduce or cancel the alternative drug.
Dosage regimes in special cases

Patients who experience severe motor fluctuations are advised to take a daily dose more than 4 times a day without changing the daily dose itself.
In the elderly, the increase in dose should occur more slowly. Experience in children and adolescents is limited.
With renal and hepatic insufficiency of mild and moderate severity, correction of the dose is not required.

When there are spontaneous movements such as chorea or athetosis in later stages of treatment, it is necessary to reduce the dose.

With prolonged use of the drug, the appearance of episodes of "hardening", the weakening of the effect at the end of the period of the action of the dose and the phenomenon of "on-off" can be eliminated or significantly reduced by reducing the dose or using the drug in a smaller dose, but more often.
Subsequently, the dose can be increased again to enhance the effect of treatment.
When there are undesirable reactions from the cardiovascular system, it is necessary to reduce the dose.

SIDE EFFECT

The frequency of unwanted reactions is classified according to the following criteria: 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%, including single messages.
From the hemopoietic system: very rarely - hemolytic anemia, transient leukopenia, thrombocytopenia.

From the side of the nervous system: often - headache, dizziness, convulsions, spontaneous movement disorders (such as chorea and athetosis), episodes of "hardening", weakening effect by the end of the dose period, the phenomenon of "on-off", increasing manifestations of the syndrome of restless legs »;
very rarely - marked drowsiness, episodes of sudden drowsiness.
Mental disorders: rarely - agitation, anxiety, depressed mood, insomnia, delirium, aggression, depression, anorexia, mild rapture, pathological gambling addiction, hypersexuality, increased libido;
very rarely - hallucinations, temporary disorientation.
From the cardiovascular system: very rarely - arrhythmias, orthostatic hypotension (weakening after a decrease in the dose of the drug), increased blood pressure;frequency is unknown - "tides".

From the digestive system: very rarely - nausea, vomiting, diarrhea, individual cases of loss or change in taste, dryness of the oral mucosa;
frequency unknown - gastrointestinal bleeding.
From the skin and subcutaneous tissues: rarely - skin itching, rash.

On the part of laboratory indicators: infrequently - transient increase in the activity of "liver" transaminases, alkaline phosphatase, increasing bilirubin concentration, increasing urea and creatinine in the blood, changing the color of urine to red, darkening when standing.

Other: frequency unknown - febrile fever, increased sweating.

CONTRAINDICATIONS

- hypersensitivity to levodopa, benserazid or to any other component of the drug;

- Severe disruption of the endocrine system;

- glaucoma;

severe liver dysfunction;

- severe renal dysfunction;

- Severe dysfunction of the cardiovascular system;

- endogenous and exogenous psychoses;

- simultaneous administration with non-selective MAO inhibitors, a combination of MAO type A and MAO type B inhibitors (which is equivalent to nonselective MAO inhibition);

- women of childbearing age who do not use reliable methods of contraception;

- Pregnancy;

- the period of breastfeeding;

- age up to 25 years.

PREGNANCY AND LACTATION

The drug Levodopa / Benserazid-Teva is contraindicated in pregnancy and women of childbearing age, who do not use reliable methods of contraception.
If the pregnancy is suspected, the drug should be immediately discontinued. If you need to take the drug, breastfeeding should be discontinued, as it is impossible to exclude the development of a skeleton in a child.
APPLICATION FOR FUNCTIONS OF THE LIVER

Contraindicated in severe renal dysfunction.
With renal failure of mild and moderate severity, dose adjustment is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Contraindicated in severe liver dysfunction.
With hepatic insufficiency of mild and moderate severity, dose adjustment is not required.
APPLICATION FOR CHILDREN

Contraindicated at the age of 25 years.

SPECIAL INSTRUCTIONS

Undesirable reactions from the gastrointestinal tract, possible at the initial stage of treatment, are largely eliminated if you take Levodopa / Benserazid-Teva with a small amount of food or liquid, as well as a slower increase in the dose.
It is not recommended to use Levodopa / Benserazid-Teva for the treatment of iatrogenic extrapyramidal syndrome and Huntington's chorea.
Patients who have a history of information about gastrointestinal ulcers, convulsions and osteomalacia, it is necessary to regularly monitor the relevant indicators.
In the process of treatment should monitor the performance of the liver, kidneys, the formula of blood. Patients who have a history of coronary heart disease, myocardial infarction, heart rhythm disturbances, it is necessary to regularly monitor the electrocardiogram.
Patients who have an orthostatic hypotension in an anamnesis should be under medical supervision, especially at the beginning of treatment.

Patients with diabetes should often monitor the concentration of glucose in the blood and adjust the dose of oral hypoglycemic drugs.
When using the drug Levodopa / Benserazid-Teva reported cases of sudden onset of sleep. Patients should be informed about a possible sudden falling asleep.
When using Levodopa / Benserazid-Teva, the risk of developing malignant melanoma increases, and therefore the use of the drug in patients with malignant melanoma, including in the anamnesis, is not recommended.
The use of Levodopa / Benserazid-Teva, especially in high doses, increases the risk of developing compulsive disorders.
Before general anesthesia, Levodopa / Benserazid-Teva should be taken as long as possible.
An exception is halothane anesthesia. Since the patient receiving the drug during the halotane anesthesia may experience fluctuations in blood pressure and arrhythmia, the drug should be withdrawn 12-24 hours before the surgery. After the operation, the treatment is renewed, gradually increasing the dose.
The drug Levodopa / Benserazid-Teva can not be abolished abruptly.
Abrupt withdrawal can lead to a "withdrawal syndrome" (fever, muscle stiffness, as well as possible mental changes and increased activity of serum creatinine phosphokinase) or akinetic crises that can take a life-threatening form. If such symptoms occur, the patient should be under the supervision of a doctor (if necessary, should be hospitalized) and receive appropriate therapy, which may include the re-use of Levodopa / Benserazid-Teva.
Depression can be a clinical manifestation of the underlying disease (Parkinsonism) and may also occur when treated with Levodopa / Benserazid-Teva.
Such patients should be under the supervision of a physician for the timely detection of mental undesirable reactions.
Some patients with Parkinson's disease noted the appearance of behavioral and cognitive disorders as a result of uncontrolled use of increasing doses of the drug, despite the doctor's recommendations and a significant increase in therapeutic doses.

The experience of using Levodopa / Benserazid-Teva under the age of 25 is limited.
Influence on the ability to drive and work with technology Patients who experience excessive daytime sleepiness or sudden episodes of sleep need to give up driving or working with machinery. If these symptoms appear during treatment with the drug Levodopa / Benserazid-Teva should consider the possibility of reducing the dose or canceling therapy.
OVERDOSE

Symptoms: increased manifestations of adverse reactions - arrhythmia, confusion, insomnia, nausea and vomiting, abnormal involuntary movements. Development overdose symptoms may be delayed due to slow absorption of the drug L-Dopa / benserazide-Teva from the gastrointestinal tract.
Treatment: symptomatic therapy - respiratory analeptic, antiarrhythmics, antipsychotics; necessary to monitor vital functions. Furthermore, it should prevent further absorption of the drug from the gastrointestinal tract by applying appropriate therapy.
DRUG INTERACTION

Pharmacokinetic interaction
With simultaneous application trihexyphenidyl (m-holinoblokator) rate reduction occurs, but not the degree of absorption of levodopa.
Ferrous sulfate reduces C max and AUC for levodopa 30-50%; These changes, in some cases, are clinically significant.
While the use of antacids extent of absorption of levodopa / benssrazida reduced by 32%.
Metoclopramide increases the rate of absorption of levodopa.
Pharmacodynamic interactions
Neuroleptics, opioids and antihypertensive medications containing reserpine inhibit the action of levodopa / benserazide. If necessary, use the lowest dose of these drugs.
With simultaneous use of pyridoxine can reduce the antiparkinsonian action of levodopa / benserazide.
Levodopa / benserazide can not be applied to non-selective MAO inhibitors. If necessary, use of levodopa / benserazide patients receiving non-selective irreversible MAO inhibitors, since discontinuation of MAO inhibitor prior to admission must be at least 2 weeks. Premature (within 2 weeks after discontinuation) the use of levodopa / benserazide nonselective inhibitor for MAO (e.g., tranylcypromine) can cause hypertensive crisis. Selective MAO-B inhibitors (including selegiline, rasagiline) and selective inhibitors of MAO type A (moclobemide) can be used during the treatment levodopa / benserazide. In certain cases, selegiline can increase the effect of levodopa / benserazide, without causing dangerous interactions.It is recommended to adjust the dose of levodopa / benserazide, depending on the individual patient's needs in terms of therapeutic efficacy and tolerability. The combination of selective MAO-B inhibitors and selective MAO inhibitors of type A is equivalent to the non-selective MAO inhibitor reception, so such a combination should not be used with levodopa / benserazide.
If necessary, use of antihypertensive drugs during treatment with levodopa / benserazide should consider the possibility of orthostatic hypotension.
Levodopa / benserazide potentiates the action of sympathomimetic (epinephrine, norepinephrine, isoproterenol, amphetamine), and therefore do not use such combination preparations. If concomitant use is still required, it is necessary to carefully monitor the state of the cardiovascular system and reduce the dose sympathomimetic if necessary.
Perhaps the use of levodopa / benserazide other antiparkinsonian drugs (anticholinergics, amantadine, dopamine receptor agonists), thus can be amplified not only desirable, but unwanted effects. It may be necessary to reduce the dose of levodopa / benserazide or another drug. With simultaneous use of levodopa / benserazide with an inhibitor of catechol-o-methyl transferase may require reduction in the dose of levodopa / benserazide. Since patients receiving levodopa / benserazide during halothane anesthesia may experience fluctuations in blood pressure and arrhythmia, you should stop taking the drug for 12-48 hours prior to surgery. Protein-rich food may reduce the therapeutic effect of levodopa / benserazide.Levodopa / benserazide may affect the results of laboratory studies of catecholamines, creatinine, uric acid, glucose, alkaline phosphatase, bilirubin. Can be determined by increasing the concentration of urea and creatinine in blood, false negative reaction for glucose in urine as determined by glucose oxidase glucose false positive Coombs' test.
TERMS OF RELEASE FROM PHARMACY

On prescription.

TERMS AND CONDITIONS OF STORAGE

At temperatures above 25 ° C in a dry place.
Keep out of the reach of children. Shelf life - 2 years.
Alphabetical index of medicines:
A  B  V  G  D  E  J
Z  I  Y  K  L  M  N
O  P  R  S  T  U  F
H  C  CH  SH  E  U  Y
Rambler's Top100
Privacy policy:
Copyright 2009 - 2017. Universal reference book of medicines. All rights reserved.
When using site materials, an active hyperlink is required!