Levodopa / Benserazid-Teva (Levodopa / Benserazide-Teva)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceLevodopa + BenserazideLevodopa + Benserazide
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    • Dosage form: & nbsppills
    Composition:
    1 tablet contains:
    active substances: levodopa 100.00 mg / 200.00 mg, benserazid (benserazide hydrochloride) 25.00 (28.50) mg / 50.00 (57.00) mg;
    Excipients: mannitol 89.15 mg / 178.30 mg, microcrystalline cellulose 4.95 mg / 9.90 mg, corn pregelatinized starch 18.70 mg / 37.40 mg, calcium hydrophosphate (anhydrous) 7.97 mg / 15.94 mg , povidone-K25 11.00 mg / 22.00 mg, crospovidone (type A) 8.25 mg / 16.50 mg, silicon dioxide colloid 0.71 mg / 1.42 mg, iron dye oxide red (E172) 0 , 27 mg / 0.54 mg, magnesium stearate 5.50 mg / 11.00 mg.
    Description:
    Dosage of 100 mg + 25 mg. Round biconvex tablets are pink in color with a light "marble" with a cross-shaped risk on both sides.
    Dosage of 200 mg + 50 mg. Round flat tablets with a bevel of pink color with a light "marble". On both sides of the tablet is a cruciform risk.On one side is the "B" and "L" engraving in the two sections of the cruciform risks.
    Pharmacotherapeutic group:Antiparkinsonian means combined (dopamine precursor + decarboxylase aromatic L-amino acids peripheral inhibitor).
    ATX: & nbsp

    N.04.B.A   Dopa and dopa derivatives

    N.04.B.A.02   Levodopa and a decarboxylase inhibitor

    Pharmacodynamics: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 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 efficiency as levodopa in high doses.
    Pharmacokinetics:
    Suction. Levodopa and benserazide are absorbed mainly in the upper parts of the small intestine. The maximum concentration in the blood plasma (Cmax) with ingestion is reached after approximately 1 hour. The area under the concentration-time curve (AUC) and Cmax are in proportion to the dose taken. 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. The half-life (T1 / 2) 3h.
    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. T1 / 2 of this main metabolite is 15 hours, and in patients receiving therapeutic doses of the drug, its accumulation takes place. Reduction of peripheral decarboxylation of levodopa,if the latter is used together with benserazide, leads to higher plasma concentrations of levodopa and 3-o-methyldopa and lower concentrations of catecholamines (dopamine, noradrenaline) 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 T1 / 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 failure correction of the dose is not required.
    In elderly patients (65-78 years) with Parkinson's T1 / 2 and AUC, levodopa increases by 25%, which is not a clinically significant change.
    Indications:Parkinson's disease.
    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 nonselective MAO inhibitors, a combination of MAO type A and MAO type B inhibitors (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.
    Dosing and Administration:
    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, prescribe an initial dose of 50 mg of levodopa / 12.5 mg of benserazide 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, taking Levodopa / Benserazid-Teva should be started 12 hours after discontinuation of 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 had previously taken levodopa in combination with an aromatic L-amino acid decarboxylase inhibitor, taking Levodopa / Benserazid-Teva should be started 12 hours after stopping the use 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 had previously taken 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, it is recommended to take a daily dose more than 4 times a day without changing the daily dose itself.
    In old age the dose increase should be slower.
    Experience of application in children and adolescents is limited.
    With renal and hepatic insufficiency of mild and moderate severity correction of the dose is not required.
    When the emergence of spontaneous movements such as chorea or athetosis at late stages of treatment it is necessary to reduce the dose.
    When prolonged use of the drug the appearance of episodes of "congealing", 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 undesirable reactions from the cardiovascular system it is necessary to reduce the dose.
    Side effects:
    The frequency of adverse reactions are classified according to the following criteria: very often - at least 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.
    On the part of the hematopoiesis system: very rarely - hemolytic anemia, transient leukopenia, thrombocytopenia.
    From the nervous system: often - headache, dizziness, convulsions, spontaneous movement disorders (such as chorea and athetosis), episodes of "hardening", the weakening effect of the end of the period of the dose, the phenomenon of "on-off", strengthening manifestations of the syndrome, "Restless Legs "; very rarely - severe sleepiness, episodes of sudden sleepiness.
    Disorders of the psyche: seldom - agitation, anxiety, depressed mood, insomnia, delusions, aggression, depression, anorexia, mild excitement, pathological gambling, 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 - "hot flashes".
    From the digestive system: very rarely - nausea, vomiting, diarrhea, individual cases of loss or changes in taste, dryness of the oral mucosa; frequency unknown - gastrointestinal bleeding.
    From the skin and subcutaneous tissues: rarely - itching of the skin, rash.
    From the laboratory indicators: infrequently, a transient increase in the activity of "liver" transaminases, alkaline phosphatase, an increase in the concentration of bilirubin, an increase in urea and creatinine in the blood, a change in the color of urine to red, darkening when standing.
    Other: frequency unknown - febrile fever, increased sweating.
    Overdose:
    Symptoms: increased manifestation of adverse reactions - arrhythmia, confusion, insomnia, nausea and vomiting, pathological involuntary movements. The development of overdose symptoms can be delayed due to the slow absorption of Levodopa / Benserazid-Teva from the digestive tract.
    Treatment: symptomatic therapy - respiratory analeptics, antiarrhythmics, antipsychotics; it is necessary to monitor vital functions. In addition, further absorption of the drug from the gastrointestinal tract should be prevented by appropriate therapy.
    Interaction:
    Pharmacokinetic interactions
    With the simultaneous use of trihexyphenidyl (m-cholinoblocker), the rate decreases, but not the degree of absorption of levodopa.
    Iron sulfate reduces Cmax and AUC of levodopa by 30-50%; these changes in some cases are clinically significant.
    With simultaneous use with antacids, the degree of absorption of levodopa / benserazide is reduced by 32%.
    Metoclopramide increases the rate of absorption of levodopa.
    Pharmacodynamic interactions
    Neuroleptics, opioids and antihypertensives containing reserpine, suppress the action of levodopa / benserazide. If necessary, use the lowest dose of these drugs.
    With simultaneous application pyridoxine can reduce the antiparkinsonian action of levodopa / benserazide.
    Levodopa / benserazide should not be used with nonselective MAO inhibitors.If it is necessary to use levodopa / benserazide, patients who receive irreversible non-selective MAO inhibitors should undergo at least 2 weeks from the moment of discontinuation of the MAO inhibitor. Premature (within 2 weeks after cancellation) the use of levodopa / benserazide in a non-selective MAO inhibitor (eg tranylcypromine) can cause a hypertensive crisis. Selective inhibitors of MAO type B (incl. selegiline, rasagiline) and selective MAO inhibitors of type A (moclobemide) can be used against the background of levodopa / benserazid treatment. 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 need for therapeutic effectiveness and tolerability. The combination of selective inhibitors of MAO type B and selective MAO inhibitors of type A is equivalent to the use of a non-selective MAO inhibitor, so a similar combination should not be used with levodopa / benserazide.
    If it is necessary to use antihypertensive drugs against the background of levodopa / benserazide treatment, it is necessary to consider the possibility of developing orthostatic hypotension.
    Levodopa / benserazid potentiates the action of sympathomimetics (epinephrine, norepinephrine, isoproterenol, amphetamine), so do not use a similar combination of drugs. If simultaneous reception is still mandatory, then carefully monitor the state of the cardiovascular system and, if necessary, reduce the dose of sympathomimetics.
    It is possible to use levodopa / benserazide with other antiparkinsonian drugs (anticholinergics, amantadine, dopamine receptor agonists), and not only desirable but also undesirable effects can be enhanced. It may be necessary to reduce the dose of levodopa / benserazide or another drug. When levodopa / benserazide is simultaneously used with a catechol-O-methyltransferase inhibitor, a dose reduction of levodopa / benserazide may be required. Since the patient receiving levodopa / benserazid during the halothane anesthesia may experience fluctuations in blood pressure and arrhythmia, it is necessary to cancel taking the drug 12-48 hours before surgery. Protein-rich foods can reduce the therapeutic effect of levodopa / benserazide.Levodopa / benserazid can affect the results of laboratory studies of catecholamines, creatinine, uric acid, glucose, alkaline phosphatase, bilirubin. An increase in the concentration of urea and creatinine in the blood, a false-negative reaction to glucose in urine when it is determined by glucose glucose oxidase, a false positive result of Coombs test can be determined.
    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" (increased body temperature, 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.
    Effect on the ability to drive transp. cf. and fur: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.
    Form release / dosage:
    Tablets 100 mg + 25 mg, 200 mg + 50 mg.
    Packaging:For 20, 30, 50, 60 or 100 tablets in a bottle of high-density polyethylene with a screw cap made of polypropylene containing silica gel and equipped with a first-opening control system. 1 bottle with instructions for use in a cardboard box.
    Storage conditions:At a temperature of no higher than 25 ° C in a place protected from moisture. Keep out of the reach of children.
    Shelf life:
    2 years.
    Do not use after expiry date.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-001827
    Date of registration:10.09.2012
    The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel
    Manufacturer: & nbsp
    Representation: & nbspTeva Teva Israel
    Information update date: & nbsp24.08.2015
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