Madopar
Madopar: 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. Drug interactions
- 11. Analogs
- 12. Terms and conditions of storage
- 13. Terms of dispensing from pharmacies
- 14. Reviews
- 15. Price in pharmacies
Latin name: Madopar
ATX code: N04BA02
Active ingredient: levodopa + benserazide (levodopa + benserazide)
Manufacturer: Roche S. p. A. (Italy), F. Hoffmann-La Roche Ltd. (Switzerland)
Description and photo update: 2019-14-08
Prices in pharmacies: from 652 rubles.
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Madopar is a combined antiparkinsonian drug.
Release form and composition
Dosage forms of Madopar:
- Hard gelatin capsules (125): size No. 2, opaque structure with a pinkish-flesh-colored body, a light blue cap and black "ROCHE" marking; inside capsules - granular powder of light beige color, sometimes crumpled (30 or 100 pcs. in glass bottles of dark color, in a cardboard box 1 bottle);
- Capsules hard gelatinous with modified release (GSS 125): size No. 1, opaque structure with a light blue body, a dark green cap and a rusty red inscription "ROCHE"; inside capsules - granular powder of yellowish or white color, sometimes crumpled (30 or 100 pcs. in glass bottles of dark color, in a cardboard box 1 bottle);
- Dispersible tablets (fast-acting) (125): flat cylindrical shape, with a beveled edge, almost white or white in color with a slight marbling of the surface, on one side there is a dividing line, on the other - engraved "ROCHE 125", with little or no odor, the diameter of the tablet is about 11 mm, the thickness is about 4.2 mm (30 or 100 pcs. in glass vials of dark color, in a cardboard box 1 bottle);
- Tablets 250: flat cylindrical shape, with a beveled edge, pale red with minor splashes, on one side engraved "ROCHE", a cruciform line and a hexagon, on the other - a cruciform dividing line; tablet diameter 12.6-13.4 mm, thickness 3-4 mm (30 or 100 pieces in dark glass bottles, 1 bottle in a cardboard box).
The active ingredients of Madopar are levodopa and benserazide hydrochloride, their content in the preparation (respectively):
- 1 capsule (size No. 2 and No. 1) - 100 mg and 28.5 mg, which is equivalent to 25 mg of benserazide;
- 1 dispersible tablet (125) - 100 mg and 28.5 mg, which is equivalent to 25 mg of benserazide;
- 1 tablet (250) - 200 mg and 57 mg, which is equivalent to 50 mg of benserazide.
Auxiliary components:
- Capsules 125: magnesium stearate, microcrystalline cellulose, povidone, talc;
- Capsules GSS 125 (modified release): mannitol, hydrogenated vegetable oil, povidone, hypromellose, calcium hydrogen phosphate, magnesium stearate, talc;
- Tablets 125: pregelatinized corn starch, anhydrous citric acid, magnesium stearate, microcrystalline cellulose;
- Tablets 250: calcium hydrogen phosphate, mannitol, microcrystalline cellulose, crospovidone, pregelatinized corn starch, ethyl cellulose, colloidal anhydrous silicon dioxide, iron oxide red dye, magnesium stearate, sodium docusate.
Composition of capsules: titanium dioxide (E171), gelatin.
Additionally as a part of capsules:
- Capsules 125: cap - indigo carmine dye (E132), body - iron oxide red dye (E172);
- GSS 125 capsules: cap - indigo carmine dye (E132), iron oxide yellow dye (E172), body - indigo carmine dye (E132).
Pharmacological properties
Pharmacodynamics
Dopamine, which acts as a neurotransmitter in the brain, is produced too little in the basal ganglia in patients with Parkinson's disease. Levodopa, or L-DOPA (4-dihydrophenylalanine), is the metabolic precursor of dopamine. Unlike the latter, this substance penetrates well through the blood-brain barrier. After levodopa enters the central nervous system, it is transformed into dopamine by decarboxylase of aromatic L-amino acids.
When taken orally, levodopa is rapidly decarboxylated to form dopamine in both extracerebral and cerebral tissues. As a result, most of the active substance does not reach the basal ganglia, and peripheral dopamine often provokes adverse reactions. For this reason, blocking of extracerebral decarboxylation of levodopa is required, which becomes possible when it is combined with benserazide, which is an inhibitor of peripheral decarboxylase of aromatic L-amino acids.
As part of Madopar, levodopa and benserazide are presented in a 4: 1 ratio. At the same time, the drug remains as effective as levodopa in significant doses.
When the drug is used to eliminate restless legs syndrome, the exact mechanism of action has not been studied, however, presumably the dopaminergic system plays an important role in the pathogenesis of this disease.
Pharmacokinetics
Madopar 125 capsules and Madopar 250 tablets
Levodopa and benserazide are predominantly absorbed in the upper sections of the small intestine (66-74% of the dose taken), and the degree of absorption does not depend on the site of absorption in this section of the intestine. The maximum plasma levodopa level is reached 1 hour after taking the tablets or capsules. Madopar 250 tablets and Madopar 125 capsules are bioequivalent when taken in an identical molar dose. The absolute bioavailability of levodopa in these dosage forms is on average 98% (the range varies from 74% to 112%). The degree of absorption of levodopa (AUC) and its maximum plasma concentrations increase in direct proportion to the dose (refers to the dose range 50-200 mg). When Madopar is taken simultaneously with food, the rate and degree of absorption of levodopa are reduced. When capsules or tablets are prescribed after meals, the maximum concentration of levodopa in the blood plasma is reduced by 30%, and the time to reach it is increased. The degree of absorption of this active ingredient is reduced by 15%.
Dispersible tablets (fast-acting) Madopar 125
After oral administration of dispersible tablets, the pharmacokinetic profiles of levodopa are similar to those after administration of Madopar 250 tablets or Madopar 125 capsules. However, maximum plasma concentrations are usually achieved in a shorter period of time. Patient absorption rates of dispersible tablets tend to be less variable.
Modopar GSS 125 Modified Release Capsules
For Madopar GSS 125, different pharmacokinetic parameters are characteristic than for other dosage forms. The active ingredients are released in the stomach at an insignificant rate. The maximum concentration of levodopa does not exceed 20-30% of that after taking Madopar 250 tablets and Madopar 125 capsules and is reached 3 hours after taking the drug. The dynamics of the concentration of the active substance in plasma is characterized by a longer "half-life" (the period of time during which the content of levodopa in the plasma exceeds or is equal to half of the maximum concentration) than Madopar 250 tablets or Madopar 125 capsules, which confirms the continuous modified release. Bioavailability of Madopar GSS 125 capsules is 50–70% of the bioavailability of Madopar 250 tablets and Madopar 125 capsules, and food intake does not affect it. The maximum concentration of levodopa also does not depend on food intake and in this case is reached 5 hours after taking this dosage form.
Levodopa crosses the blood-brain barrier via a saturable transport system. There is no plasma protein binding. The volume of distribution is 57 liters. The area under the concentration-time curve (AUC) for levodopa in cerebrospinal fluid is 12% of that in plasma. When Madopar is taken in recommended doses, benserazide does not penetrate the blood-brain barrier and is predominantly accumulated in the liver, small intestine, kidneys and lungs.
Levodopa is metabolized by two main (o-methylation and decarboxylation) and two side (oxidation and transamination) pathways. Levodopa is converted to dopamine by aromatic L-amino acid decarboxylase. The main end products of this metabolic pathway are dihydroxyphenylacetic and homovanillic acids.
Catechol-O-methyltransferase is involved in the methylation of levodopa, which results in the formation of 3-O-methyldopa. The half-life of this main metabolite from plasma is 15-17 hours, and in patients taking Madopar in the recommended doses, it accumulates. When administered together with benserazide, levodopa undergoes peripheral decarboxylation to a lesser extent, which leads to higher plasma concentrations of levodopa and 3-O-methyldopa and a lower content of phenol carboxylic acids (dihydrophenylacetic acid, homovanilic acid) and catecholamines (plasmidamine), dopamine.
In the liver and intestinal mucosa, benserazide is hydrolyzed, and the final product of the process is trihydroxybenzylhydrazine. This metabolite is a potent inhibitor of aromatic L-amino acid decarboxylase.
With peripheral inhibition of aromatic L-amino acid decarboxylase, the half-life of levodopa is 1.5 hours. The clearance of the substance from the plasma is approximately 430 ml / min.
Benserazide is almost completely eliminated by participation in metabolic processes. Excretion of metabolites is carried out mainly through the kidneys (64%) and to a lesser extent through the intestines (24%).
There is no information on the pharmacokinetics of levodopa in patients with hepatic and renal insufficiency. In elderly patients (65-78 years old) suffering from Parkinson's disease, AUC and half-life increase by 25%, which does not refer to clinically significant changes and does not require correction of the dosage regimen.
Indications for use
According to the instructions, Madopar is indicated for patients with Parkinson's disease:
- Idiopathic Restless Legs Syndrome;
- Restless legs syndrome in patients with chronic renal failure on dialysis.
In addition, for dysphagia and akinesia in the morning and evening, patients with the phenomenon of "depletion of the effect of a single dose" or the phenomenon of "increase in the latency period before the onset of the clinical effect of the drug" are prescribed dispersible fast-acting tablets 125.
For any types of fluctuations in the action of levodopa ("dyskinesia of the peak dose" or "the phenomenon of the end of the dose", including immobility at night), the use of Madopar GSS 125 capsules is indicated.
Contraindications
- Mental pathologies with a psychotic component;
- Decompensated dysfunction of the organs of the endocrine system;
- Cardiovascular diseases in the stage of decompensation;
- Decompensated liver dysfunction;
- Decompensated renal dysfunction (except for patients with restless legs syndrome on dialysis);
- Simultaneous use of non-selective inhibitors of monoamine oxidase (MAO), a combination of MAO type A and MAO type B inhibitors;
- Closed-angle glaucoma;
- Age under 25;
- The period of pregnancy and breastfeeding;
- Hypersensitivity to drug components.
Taking Madopar is contraindicated in women of childbearing age who do not use reliable methods of contraception.
Instructions for use Madopar: method and dosage
Madopar is taken orally half an hour before or 1 hour after a meal.
Capsules are swallowed whole, it is not recommended to open Madopar GSS 125 capsules, as this will cause a loss of the effect of modified release of the active substance.
Tablets 250 can be crushed to facilitate swallowing, dispersible tablets are dissolved in 25-50 ml of water before use. The tablet dissolves within a few minutes, the resulting milky-white solution must be taken in the next half hour by mixing it thoroughly.
The use of Madopar begins with a gradual selection of an individual dose that provides an optimal therapeutic effect.
Recommended dosage:
- The initial stage of the disease: treatment should begin with taking the drug at a dose of 50 mg / 12.5 mg (levodopa / benserazide) 3-4 times a day. Given the tolerance of Madopar to patients, it is recommended to increase the dose gradually. The optimal clinical effect is achieved within 4-6 weeks, usually with a daily dose of 300-800 mg / 75-200 mg in 3 or more doses. If necessary, proceed to a further increase in the daily dose should not earlier than after 1 month;
- Maintenance dose: 100 mg / 25 mg 3-6 times a day, dispersible tablets or GSS 125 capsules should be used to optimize the effect;
- Syndrome of "restless legs": the drug is taken 1 hour before bedtime with meals, no more than 400 mg / 100 mg (500 mg Madopar) per day;
- Idiopathic Restless Legs Syndrome with sleep disorders: 125 capsules or 250 tablets should be taken, starting dose 50 mg / 12.5 mg-100 mg / 25 mg (levodopa / benserazide). To achieve a clinical effect, the dose should be increased to 200 mg / 50 mg;
- Idiopathic "restless legs" syndrome with sleep and sleep disorders: the initial dose is 1 capsule of GSS 125 and 1 capsule 125 1 hour before going to bed. If necessary, the dose of GSS 125 should be increased to 2 capsules;
- Idiopathic syndrome of "restless legs" with disorders of falling asleep, sleeping and during the day: additionally - 1 dispersible tablet or 1 capsule 125, but not more than 400 mg / 100 mg (500 mg Madopar) per day;
- Syndrome of "restless legs" against the background of chronic renal failure in patients receiving dialysis: 1 capsule 125 or 1 dispersible tablet half an hour before the start of dialysis.
In the case of the appointment of Madopar in combination with other antiparkinsonian drugs, it may be necessary to reduce their dose or gradually cancel it.
Dispersible tablets (fast-acting) - a special form of Madopar for patients with akinesia or dysphagia in the morning and evening, the phenomena of "depletion of the effect of a single dose" or "increase in the latency period before the onset of the clinical effect of the drug." If the phenomenon of "depletion of the effect of a single dose" or the phenomenon of "on-off" occurs during the day, the patient should be transferred to a more frequent intake of the drug in smaller single doses or (and this is preferable) to the use of GSS 125 capsules.
It is advisable to start the transition to GSS 125 by taking the morning dose corresponding to dispersible tablets or 250 tablets, while it is recommended to maintain the therapy regimen.
Gradually increase the dose (by about 50%) after 2-3 days. Patients should be warned about the possible temporary deterioration of the condition during this period, since the effect of GSS 125 begins somewhat later.
To achieve a faster clinical effect, it is recommended that GSS 125 be combined with capsules 125 or dispersible tablets (fast-acting). This combination is optimal for the first morning dose.
The dose of GSS 125 must be selected carefully and slowly, with a break of 2-3 days or more between changes.
To achieve a positive effect in patients with symptoms manifested at night, a gradual increase in the evening dose (before bedtime) of GSS 125 to 2 capsules is recommended.
When dyskinesia appears while taking GSS 125, the intervals between doses should be increased (this gives a greater effect than reducing a single dose).
If Madopar GSS 125 is not effective enough, you should return to the previously used forms of the drug.
Long-term therapy can cause the appearance of the phenomenon of "exhaustion", episodes of "freezing", the phenomenon of "on-off". Special cases of the dosing regimen consist in crushing the daily dose of the drug, that is, in reducing a single dose or shortening the interval between doses of the drug with the phenomenon of "exhaustion" and episodes of "freezing", and with the phenomenon of "on-off" - in reducing the number of doses with an increase in the single dose. Then you can try again to increase the dose for the effectiveness of the treatment.
Dose adjustment is not required in patients with mild to moderate renal insufficiency. Madopar is well tolerated by patients on hemodialysis.
To exclude aggravation of the symptoms of restless legs syndrome, the daily dose of Madopar should not exceed 400 mg / 100 mg (levodopa / benserazide).
In case of an increase in clinical symptoms, the patient should reduce the dose of levodopa or gradually switch to the use of other drugs.
Side effects
- Digestive system: diarrhea, nausea, vomiting; in some cases - dryness of the oral mucosa, change or loss of taste;
- Nervous system: insomnia, agitation, anxiety, hallucinations, temporary disorientation (especially in elderly patients and with a history of these symptoms), delirium, depression, dizziness, headache; (in the later stages of therapy) sometimes - severe drowsiness, spontaneous movements (such as athetosis or chorea), episodes of "freezing", the phenomenon of "exhaustion" (weakening of the effect by the end of the dose period), episodes of sudden drowsiness, the phenomenon of "on-off", worsening of restless legs syndrome;
- Cardiovascular system: orthostatic hypotension (with a decrease in the dose of Madopar weakens), arrhythmias, arterial hypertension;
- Hematopoietic system: rarely - transient leukopenia, hemolytic anemia, thrombocytopenia;
- Respiratory system: rhinitis, bronchitis;
- From the body as a whole: anorexia;
- Dermatological reactions: rarely - itching, rash;
- Laboratory indicators: sometimes - an increase in gamma-glutamyl transpeptidase, blood urea nitrogen, a transient increase in the activity of liver enzymes and alkaline phosphatase, a change in the color of urine to red (when standing, it turns dark);
- Others: febrile infection.
Overdose
An overdose of Madopar is expressed by symptoms, referred to in the instructions as side effects, but in a more pronounced form. These are manifestations from the side of the cardiovascular system (arrhythmias), from the gastrointestinal tract (nausea and vomiting) and the mental sphere (insomnia, blurred consciousness), as well as pathological involuntary movements.
When taking capsules of the drug with modified release (Madopar GSS 125), overdose symptoms may be observed later due to the reduced rate of absorption of active ingredients in the stomach.
In case of an overdose, it is necessary to monitor vital functions. It is also recommended symptomatic treatment with the use of antiarrhythmics, respiratory analeptics, and, where appropriate, antipsychotics. When taking capsules with modified release of active ingredients (Madopar GSS 125), it is advisable to prevent subsequent absorption of Madopar.
special instructions
To significantly reduce the risk of adverse reactions from the digestive system, you should always take Madopar with a small amount of liquid or food and slowly increase the dose.
In patients with open-angle glaucoma, intraocular pressure should be monitored regularly.
The content of levodopa in the drug requires periodic monitoring of liver and kidney function, blood counts.
Patients with diabetes mellitus need to adjust the dose of hypoglycemic agents and frequent monitoring of blood glucose levels.
Before general anesthesia, the drug should be taken as long as possible, except in the case of the appointment of halothane anesthesia, which against the background of Madopar can cause fluctuations in blood pressure (BP) and arrhythmia. Therefore, with halothane anesthesia, it is recommended to stop taking the drug 12-48 hours before general anesthesia. After surgery, treatment is resumed with low doses and gradually increased to the previous level.
It is impossible to abruptly cancel the drug, this can cause the development of a malignant neuroleptic syndrome, the characteristic signs of which are muscle rigidity, an increase in body temperature and the level of creatine phosphokinase in the blood serum, mental changes. Since the syndrome can take a form that poses a threat to the patient's life, it requires careful medical supervision and the appointment of appropriate symptomatic therapy.
The use of the drug must be accompanied by regular observation of the patient for the possible appearance of adverse mental reactions. Depression can occur both during therapy and be a clinical manifestation of parkinsonism.
Uncontrolled use of increasing doses of the drug can cause behavioral and cognitive disorders.
In the event of drowsiness or sudden episodes of drowsiness, the dose should be reduced or Madopar should be canceled, the patient during this period must refuse to drive vehicles and mechanisms.
Application during pregnancy and lactation
Pregnant women and women of reproductive age who do not use reliable methods of contraception should never take Madopar due to the high risk of developing skeletal disorders in the fetus. If pregnancy occurs against the background of drug treatment, it should be immediately canceled, after consulting with your doctor.
If it is necessary to take Madopar during lactation, breastfeeding is recommended to be stopped immediately, since there is no reliable data on the penetration of benserazide into breast milk. The threat of incorrect skeletal formation in a newborn cannot be completely ruled out.
Drug interactions
The simultaneous use of other drugs is indicated only as directed by the attending physician, who, taking into account the clinical condition and possible concomitant pathologies of the patient, will give recommendations to avoid the development of severe adverse reactions.
Analogs
The analogues of Madopar are: Cyclodol, Pronoran, Vinpotropil, Eldepril, Yumex, Stalevo, Neomidantan, Levodopa / Benserazid-Teva.
Terms and conditions of storage
Keep out of the reach of children.
Store in a dry place at temperatures: capsules - up to 30 ° C, tablets - up to 25 ° C.
Shelf life: capsules and dispersible tablets - 3 years, Madopar 250 mg tablets - 4 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Madopar
On the network you can find diametrically different reviews about Madopar. Some patients note that with long-term treatment (over several months) of parkinsonism with the drug, positive dynamics were observed: trembling and convulsive movements disappeared, confidence in movement appeared and the ability to independently regulate movements. However, other patients complain that they did not notice significant improvements in their condition during treatment with Madopar, and in some cases, physical activity even decreased.
Price for Madopar in pharmacies
The price of Madopar in the form of 125 mg capsules is approximately 735-760 rubles (the package includes 100 pcs.). You can buy Madopar GSS 125 mg capsules with modified release for an average of 835-858 rubles (the package contains 100 pieces). The cost of dispersible tablets Madopar 125 varies from 840 to 878 rubles (the package includes 100 pcs.). Madopar 250 tablets will cost about 1350-1400 rubles (the package contains 100 pcs.).
Madopar: prices in online pharmacies
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Drug name Price Pharmacy |
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Madopar 125 100 mg + 25 mg capsules 100 pcs. 652 r Buy |
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Madopar fast acting tablets 100 mg + 25 mg dispersible tablets 100 pcs. 719 RUB Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
