Levodopa/Benserazide-Teva, 200 mg+50 mg, tablets, 100 pcs.
Inside
, 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 a therapeutic effect is achieved. High doses should be avoided when taking the drug simultaneously.
The following dosage regimen instructions should be considered as general recommendations.
For patients who have not previously taken levodopa,
an initial dose of 50 mg levodopa/12.5 mg benserazide is prescribed 2–4 times a day (from 100–200 mg levodopa/25–50 mg benserazide per day). If well tolerated, the dose is increased by 50–100 mg levodopa/12.5–25 mg benserazide every 3 days until a therapeutic effect is achieved.
Further (after the initial) dose selection is carried out once a month. Typically, a therapeutic effect is observed when taking 200–400 mg of levodopa/50–100 mg of benserazide per day.
The maximum daily dose is 800 mg levodopa/200 mg benserazide.
The daily dose should be divided into 4 or more doses. The frequency of doses should be distributed to ensure optimal therapeutic effect.
If adverse reactions occur, it is necessary to either stop increasing the dose or reduce the daily dose.
The optimal therapeutic effect is usually achieved when taking 300–800 mg levodopa/100–200 mg benserazide.
For patients who have previously taken levodopa,
Levodopa/Benserazide-Teva should be started 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 already achieved therapeutic effect. If necessary, the dose is increased according to the scheme described for patients who have not previously taken levodopa.
For patients who have previously taken levodopa in combination with an aromatic L-amino acid decarboxylase inhibitor,
Levodopa/Benserazide-Teva should be started 12 hours after stopping levodopa in combination with an aromatic L-amino acid decarboxylase inhibitor. To minimize the decrease in the already achieved therapeutic effectiveness, it is necessary to stop the previous therapy at night and start taking the drug Levodopa/Benserazide-Teva the next morning. If necessary, the dose is increased according to the scheme described for patients who have not previously taken levodopa.
For patients who have previously taken other antiparkinsonian drugs,
taking the drug Levodopa/Benserazide-Teva is possible. As soon as the therapeutic effect of Levodopa/Benserazide-Teva becomes apparent, it is necessary to reconsider the treatment regimen and reduce or discontinue the alternative drug.
Dosage regimens in special cases
Patients who experience severe motor fluctuations
It is recommended to take the daily dose more than 4 times a day without changing the daily dose itself.
In old age
Dose increases should occur more slowly.
Experience of use in children and adolescents
limited.
For renal and liver failure
mild to moderate dose adjustment is not required.
When spontaneous movements such as chorea or athetosis occur
in the later stages of treatment it is necessary to reduce the dose.
With long-term use of the drug
The occurrence of freezing episodes, weakening of the effect towards the end of the dose period and the on-off phenomenon can be eliminated or significantly reduced by reducing the dose or using a lower dose more often. Subsequently, the dose can be increased again to enhance the effect of treatment.
If adverse reactions occur from the cardiovascular system
it is necessary to reduce the dose.
Levodopa/Benserazide tablets 200mg+50mg No. 100
A country
Hungary
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.
Active substance
Levodopa + Benserazide
Compound
mannitol - 89.15 mg, microcrystalline cellulose - 4.95 mg, pregelatinized corn starch - 18.7 mg, calcium hydrogen phosphate (anhydrous) - 7.97 mg, povidone K25 - 11 mg, crospovidone (type A) - 8.25 mg, colloidal silicon dioxide - 0.71 mg, dye red iron oxide (E172) - 0.27 mg, magnesium stearate - 5.5 mg, mannitol - 178.3 mg, microcrystalline cellulose - 9.9 mg, pregelatinized corn starch - 37.4 mg, calcium hydrogen phosphate (anhydrous) - 15.94 mg, povidone K25 - 22 mg, crospovidone (type A) - 16.5 mg, colloidal silicon dioxide - 1.42 mg, red iron oxide dye (E172) - 0.54 mg, magnesium stearate - 11 mg.
pharmachologic effect
Levodopa/benserazide is a combined antiparkinsonian drug containing a dopamine precursor and an inhibitor of peripheral aromatic L-amino acid decarboxylase. In Parkinsonism, the neurotransmitter dopamine is produced in the basal ganglia in insufficient quantities. Replacement therapy is carried out by using levodopa, a direct metabolic precursor of dopamine. Most of levodopa is converted to dopamine in peripheral tissues (intestines, liver, kidneys, heart, stomach), which is not involved in the antiparkinsonian effect, since peripheral dopamine does not penetrate the blood-brain barrier (BBB) well, and is also responsible for most of its adverse reactions. Blocking extracerebral decarboxylation of levodopa is highly desirable. This is achieved by the simultaneous administration of levodopa and benserazide, an inhibitor of peripheral aromatic L-amino acid decarboxylase, 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, on the one hand, to a decrease manifestations of adverse reactions of levodopa - on the other. A 4:1 combination of these substances is as effective as high-dose levodopa.
Mode of application
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 a therapeutic effect is achieved. High doses should be avoided when taking the drug simultaneously. The dosing instructions below should be considered as general recommendations. For patients who have not previously taken levodopa, an initial dose of 50 mg levodopa / 12.5 mg benserazide 2-4 times a day is prescribed (from 100-200 mg levodopa / 25- 50 mg benserazide per day). If well tolerated, 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 once a month. Typically, a therapeutic effect is observed when taking 200-400 mg of levodopa / 50-100 mg of benserazide per day. The maximum daily dose is 800 mg of levodopa / 200 mg of benserazide. The daily dose should be divided into 4 or more doses. The frequency of doses should be distributed to ensure optimal therapeutic effect. If adverse reactions occur, it is necessary to either stop increasing the dose or reduce the daily dose. The optimal therapeutic effect is achieved, as a rule, when taking 300-800 mg of levodopa / 100-200 mg of benserazide. For patients who have previously taken levodopa, taking the drug Levodopa / Benserazide - Teva should be started 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 already achieved therapeutic effect. If necessary, the dose is increased according to the scheme described for patients who have not previously taken levodopa. For patients who have previously taken levodopa in combination with an aromatic L-amino acid decarboxylase inhibitor, Levodopa/Benserazide-Teva should be started 12 hours after discontinuation of levodopa in combination with an aromatic L-amino acid decarboxylase inhibitor. To minimize the decrease in the already achieved therapeutic effectiveness, it is necessary to stop the previous therapy at night and start taking the drug Levodopa/Benserazide-Teva the next morning. If necessary, the dose is increased according to the scheme described for patients who have not previously taken levodopa. Patients who have previously taken other antiparkinsonian drugs can take Levodopa/Benserazide-Teva. As soon as the therapeutic effect of Levodopa/Benserazide-Teva becomes apparent, it is necessary to reconsider the treatment regimen and reduce or discontinue the alternative drug. Dosage regimens in special cases For patients who experience severe motor fluctuations, it is recommended to take the daily dose more than 4 times a day without changing the daily dose itself. In old age, dose increases should occur more slowly. Experience with use in children and adolescents is limited. For mild to moderate renal and hepatic failure, no dose adjustment is required. If spontaneous movements such as chorea or athetosis occur in the later stages of treatment, it is necessary to reduce the dose. With long-term use of the drug, episodes of “freezing” appear, weakening of the effect towards the end of the dosage period and the on-off phenomenon can be eliminated or significantly reduced by reducing the dose or using the drug in a lower dose, but more often. Subsequently, you can increase the dose again to enhance the effect of treatment. If adverse reactions from the cardiovascular system occur, it is necessary to reduce the dose. Levodopa/Benserazide-Teva is contraindicated during pregnancy and in women of childbearing age who do not use reliable methods of contraception. If pregnancy is suspected, the drug should be discontinued immediately. If it is necessary to take the drug, breastfeeding should be stopped, since skeletal development disorders in the child cannot be ruled out. Contraindicated under the age of 25 years.
Interaction
Pharmacokinetic interactions: With simultaneous use of trihexyphenidyl (m-anticholinergic), the rate, but not the extent, of absorption of levodopa decreases. Ferrous sulfate reduces the Cmax and AUC of levodopa by 30-50%; these changes in some cases are clinically significant. When used simultaneously with antacids, the degree of absorption of levodopa/bensrazide is reduced by 32%. Metoclopramide increases the rate of absorption of levodopa. Pharmacodynamic interactions: Neuroleptics, opioids and antihypertensive drugs containing reserpine inhibit the effect of levodopa/benserazide. If necessary, use the lowest doses of these drugs. When used simultaneously, pyridoxine may reduce the antiparkinsonian effect of levodopa/benserazide. Levodopa/benserazide should not be used with non-selective MAO inhibitors. If it is necessary to use levodopa/benserazide in patients receiving irreversible non-selective MAO inhibitors, at least 2 weeks should pass from the moment of stopping the MAO inhibitor before starting treatment. Premature (within 2 weeks after discontinuation) use of levodopa/benserazide after a non-selective MAO inhibitor (for example, tranylcypromine) can cause a hypertensive crisis. Selective MAO type B inhibitors (including selegiline, rasagiline) and selective MAO type A inhibitors (moclobemide) can be used during treatment with levodopa/benserazide. In certain cases, selegiline may increase the effect of levodopa/benserazide without causing a dangerous interaction. It is recommended to adjust the dose of levodopa/benserazide depending on the individual needs of the patient in terms of therapeutic efficacy and tolerability. The combination of selective MAO type B inhibitors and selective MAO type A inhibitors is equivalent to taking a non-selective MAO inhibitor, so this combination should not be used with levodopa/benserazide. If it is necessary to use antihypertensive drugs during treatment with levodopa/benserazide, the possibility of developing orthostatic hypotension must be taken into account. Levodopa/benserazide potentiates the effect of sympathomimetics (epinephrine, norepinephrine, isoproterenol, amphetamine), so this combination of drugs should not be used. If simultaneous use is still necessary, then the state of the cardiovascular system should be carefully monitored and, if necessary, reduce the dose of sympathomimetics. It is possible to use levodopa/benserazide with other antiparkinsonian drugs (anticholinergic drugs, amantadine, dopamine receptor agonists), and not only the desired effects may be enhanced , but also undesirable effects. It may be necessary to reduce the dose of levodopa/benserazide or other drug. When levodopa/benserazide is used concomitantly with a catechol-O-methyltransferase inhibitor, a dose reduction of levodopa/benserazide may be required. Since a patient receiving levodopa/benserazide may experience fluctuations in blood pressure and arrhythmias during halothane anesthesia, it is necessary to stop taking the drug 12-48 hours before surgery. Protein-rich foods may reduce the therapeutic effect of levodopa/benserazide. Levodopa/benserazide may affect laboratory results of catecholamines, creatinine, uric acid, glucose, alkaline phosphatase, and bilirubin. An increase in the concentration of urea and creatinine in the blood, a false negative reaction to glucose in the urine when determined by the glucose glucose oxidase method, and a false positive result from the Coombs test can be detected.
Side effect
The incidence of adverse reactions is 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 isolated reports. From the hematopoietic 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 “freezing”, weakening of the effect towards the end of the dose period, the “on-off” phenomenon, increased manifestations of “restless legs” syndrome; very rarely - severe drowsiness, episodes of sudden drowsiness. Mental disorders: rarely - agitation, anxiety, depressed mood, insomnia, delirium, aggression, depression, anorexia, moderate delight, pathological gambling, hypersexuality, increased libido; very rarely - hallucinations, temporary disorientation. From the cardiovascular system: very rarely - arrhythmias, orthostatic hypotension (weakens after reducing the dose of the drug), increased blood pressure; frequency unknown - “hot flashes”. From the digestive system: very rarely - nausea, vomiting, diarrhea, isolated cases of loss or change in taste, dryness of the oral mucosa; frequency unknown - gastrointestinal bleeding. From the skin and subcutaneous tissues: rarely - itching of the skin, rash. From laboratory parameters: infrequently - transient increase in the activity of “liver” transaminases, alkaline phosphatase, increased concentration of bilirubin, increased urea and creatinine in the blood, change in urine color to red, darkening when standing. Other: frequency unknown - febrile fever, excessive sweating.
Contraindications
- hypersensitivity to levodopa, benserazide or to any other component of the drug; - severe dysfunction of the endocrine system; - glaucoma; - severe impairment of liver function; - severe impairment of kidney function; - severe impairment of the function of the cardiovascular system; - endogenous and exogenous psychoses; - simultaneous use with non-selective MAO inhibitors, a combination of MAO type A and MAO type B inhibitors (which is equivalent to non-selective MAO inhibition); - women of childbearing age who do not use reliable methods of contraception; - pregnancy; - breastfeeding period; - age up to 25 years.
Overdose
Symptoms: increased manifestation of undesirable reactions - arrhythmia, confusion, insomnia, nausea and vomiting, pathological involuntary movements. The development of overdose symptoms may be delayed due to delayed absorption of the drug Levodopa/Benserazid-Teva from the gastrointestinal 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 using appropriate therapy.
special instructions
Adverse reactions from the gastrointestinal tract, possible at the initial stage of treatment, are largely eliminated if you take the drug Levodopa/Benserazide-Teva with a small amount of food or liquid, as well as a slower dose increase. The use of Levodopa/Benserazide-Teva for the treatment of iatrogenic extrapyramidal syndrome and Huntington's chorea is not recommended. Patients with a history of gastrointestinal ulcers, convulsions and osteomalacia should be regularly monitored for relevant indicators. During treatment, indicators of liver function, kidney function, and blood count should be monitored. Patients with a history of coronary heart disease, myocardial infarction, or cardiac arrhythmias should have their electrocardiogram regularly monitored. Patients with a history of orthostatic hypotension should be under medical supervision, especially at the beginning of treatment. Patients with diabetes mellitus should frequently monitor glucose concentrations in the blood and adjust the dose of oral hypoglycemic drugs. Cases of sudden onset of sleep have been reported with the use of Levodopa/Benserazide-Teva. Patients should be informed about the possibility of sudden falling asleep. When using the drug Levodopa/Benserazide-Teva, the risk of developing malignant melanoma increases, and therefore the use of the drug in patients with malignant melanoma, including a history of it, is not recommended. The use of Levodopa/Benserazide-Teva, especially in high doses, increases the risk of developing compulsive disorders. Before general anesthesia, Levodopa/Benserazide-Teva should be taken for as long a period as possible. An exception is halothane anesthesia. Since the patient receiving the drug may experience fluctuations in blood pressure and arrhythmias during halothane anesthesia, the drug should be discontinued 12-24 hours before surgery. After surgery, treatment is resumed, gradually increasing the dose. Levodopa/Benserazid-Teva should not be discontinued abruptly. Abrupt withdrawal of the drug can lead to a “withdrawal syndrome” (fever, muscle stiffness, as well as possible mental changes and increased creatinine phosphokinase activity in the blood serum) or akinetic crises, which can take a life-threatening form. If such symptoms occur, the patient should be under the supervision of a physician (if necessary, should be hospitalized) and receive appropriate therapy, which may include repeated use of the drug Levodopa/Benserazide-Teva. Depression may be a clinical manifestation of the underlying disease (parkinsonism) and may also occur against treatment with Levodopa/Benserazide-Teva. Such patients should be under the supervision of a physician for the timely identification of psychiatric adverse reactions. Some patients with Parkinson's disease have experienced the emergence 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. Experience with Levodopa/Benserazide- Teva under 25 years of age is limited. Impact on the ability to drive and operate machinery Patients who experience excessive daytime sleepiness or sudden sleep episodes should avoid driving or operating machinery. If these symptoms occur during treatment with Levodopa/Benserazide-Teva, dose reduction or discontinuation of therapy should be considered.
Dispensing conditions in pharmacies
On prescription
Levodopa + Benserazide
To assess the incidence of adverse events, the following World Health Organization classification is used: very common (≥ 1/10), common (> 1/100 and < 1/10), uncommon (≥ 1/1000 and < 1/100), rare ( ≥ 1/10000 and < 1/1000), very rare (< 1/10000), frequency unknown (cannot be calculated based on available data).
Blood and lymphatic system disorders
Rarely, hemolytic anemia, moderate and transient leukopenia and thrombocytopenia, as well as a reduction in thromboplasty time were observed.
When using the drug Levodopa + Benserazide, an increase in blood urea nitrogen (BUN) levels was observed. In this regard, it is necessary to regularly monitor general blood count indicators and liver and kidney function, as is the case during long-term therapy with any drugs containing levodopa.
Metabolic and nutritional disorders
Uncommon: anorexia.
Typically, a mild, transient increase in the activity of transaminases (aspartate aminotransferase (AST), alanine aminotransferase (ALT)) and alkaline phosphatase. An increase in gammaglutamyltransferase activity was observed.
Mental disorders
Patients with Parkinson's disease may develop depression, especially in older patients or patients with a history of these symptoms; infrequently, agitation, anxiety, sleep disturbances, hallucinations, delusions, behavioral disorders and aggression may occur; rarely - nightmares and temporary disorientation.
When using the drug Levodopa + Benserazide, depression may develop, accompanied by suicidal thoughts, which can also be caused by the underlying disease.
When using the drug Levodopa + Benserazide, disorders of habits and desires, additive behavioral disorders, as well as behaviors characteristic of obsessive-compulsive disorders (compulsive buying and spending money, compulsive overeating and bulimia) may occur. Gambling behavior and increased libido, including hypersexuality, have been reported (see section "Special Instructions").
Dopamine dysregulation syndrome.
Nervous system disorders
Patients taking Levodopa + Benserazide may develop restless legs syndrome.
Uncommon: headache.
The use of Levodopa + Benserazide is accompanied by the development of drowsiness and very rarely pronounced daytime sleepiness and episodes of sudden falling asleep (see section “Special instructions”).
When taking high doses or in later stages of treatment, patients with Parkinson's disease may experience involuntary movements (for example, chorea or athetosis). As a rule, this phenomenon can be alleviated or completely eliminated by reducing the dose.
With prolonged treatment, there may be fluctuations in the therapeutic response, including episodes of "freeze-off", weakening of the effect towards the end of the dose period (the "depletion" phenomenon), the "on-off" phenomenon, which can usually be eliminated or alleviated by titrating the dose and taking small doses over short periods of time. time intervals. Subsequently, it is possible to increase the dose again in order to enhance the therapeutic effect. Isolated cases of disturbances or loss of taste sensations have been observed.
Patients with restless legs syndrome
The most common adverse effect of long-term use of dopaminergic drugs is deterioration of the patient's condition, expressed as a shift in the time of onset of symptoms from the evening/night to the day and evening before the next evening dose.
Cardiovascular disorders
Uncommon: arrhythmias, orthostatic hypotension. As a rule, the manifestations of orthostatic hypotension can be alleviated by reducing the dose of Levodopa + Benserazide.
Gastrointestinal disorders
Uncommon: decreased appetite, nausea, vomiting, diarrhea, dry mouth.
These side effects, which usually appear early in treatment, can be controlled by taking Levodopa + Benserazide with food (along with sufficient food or liquid) or by gradually increasing the dose.
Skin and subcutaneous tissue disorders
Rarely: allergic reactions (itching, rash).
Renal and urinary tract disorders
There may be a slight change in the color of urine (as a rule, it acquires a tint and darkens as it sits).
Laboratory and instrumental data
There may be a temporary increase in the activity of “liver” transaminases (AST, ALT) and alkaline phosphatase. An increase in gammaglutamyltransferase activity and an increase in blood urea nitrogen concentration were observed.
In addition, there may be discoloration or staining of body fluids or tissues, particularly saliva, tongue, teeth, or oral mucosa.
