Madopar - instructions for use, reviews, analogs and forms of release (capsules 125, tablets 250, GSS, high-speed dispersible) drugs for the treatment of Parkinson's disease, motor disorders in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Madopar. There are reviews of visitors to the site - consumers of this medication, as well as opinions of medical experts on the use of Madopar in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues Madopara in the presence of existing structural analogues.Use for the treatment of Parkinson's disease, motor disorders in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

Madopar - A combined antiparkinsonian preparation containing a dopamine precursor and an inhibitor of peripheral decarboxylases.

With parkinsonism, the neuromediator of the brain dopamine is formed in the basal ganglia in insufficient quantities. Levodopa, or L-DOPA - (3,4-dihydrophenylalanine), is a metabolic precursor of dopamine and unlike the latter it penetrates well through the BBB. After levodopa penetrates into the central nervous system, it is converted to dopamine with the help of decarboxylase aromatic acids.

Parkinson's disease

After ingestion, levodopa is rapidly decarboxylated into dopamine in both cerebral and extracerebral tissues. As a result, most of the introduced levodopa does not reach the basal ganglia, and peripheral dopamine often causes side reactions. Therefore, it is necessary to block extracerebral decarboxylation of levodopa. This is achieved by the simultaneous administration of levodopa and benserazide, an inhibitor of peripheral decarboxylase.

Madopar is a combination of these substances in a ratio of 4: 1, which is optimal and has the same efficacy as levodopa in high doses.

High-speed (dispersible) tablets are especially indicated for patients with dysphagia, as well as for patients requiring a faster onset of action of the drug.

Capsules HSA - a special dosage form with delayed release of active substances in the stomach. The maximum concentration in the plasma is 20-30% less than when taking Madopar 125 capsules and Madopar 250 tablets, and is reached 3 hours after ingestion.

Syndrome of "restless legs"

The exact mechanism of restless legs syndrome is unknown, but the dopaminergic system plays an important role in the pathogenesis of this syndrome.

Composition

Levodopa + Benserazide hydrochloride + excipients.

Pharmacokinetics

Suction

Capsules Madopar 125 and tablets Madopar 250

Levodopa and benserazide are absorbed mainly in the upper parts of the small intestine. Absolute bioavailability of levodopa averages 98% (74-112%). Capsules and Madopar tablets are bioequivalent. Eating food reduces the rate and extent of absorption of levodopa.When appointing Madopar after regular meals Cmax levodopa in plasma is 30% smaller and is reached later. The degree of absorption of levodopa decreases by 15%.

Madopar high-speed tablets (dispersible) 125

Pharmacokinetic profiles of levodopa after taking Madopar in this dosage form are similar to those after taking Madopara tablets and capsules. The absorption parameters of high-speed tablets (dispersible) in different patients are less variable than when using conventional dosage forms.

Madopar GSS 125, Modified Release Capsules

Madopar HSA 125 has other pharmacokinetic properties than conventional and dispersible forms of release. Active substances are released slowly in the stomach. The dynamics of plasma concentration is characterized by a longer half-life than conventional dosage forms, which convincingly indicates a continuous modifiable release of active substances. Bioavailability Madopara GSS 125 is 50-70% of the bioavailability of Madopar capsules 125 tablets Madopar 250 and does not depend on food intake. Food intake does not affect Cmax levodopa, which is achieved 5 hours after taking Madopar GSS 125.

Distribution

Levodopa penetrates the blood-brain barrier (GEB) through a saturated transport system. Does not bind to plasma proteins. Benserazid in therapeutic doses does not penetrate the BBB. It accumulates mainly in the kidneys, lungs, small intestine and liver.

Metabolism

Levodopa is metabolized by two major (decarboxylation and o-methylation) and two by-products (transamination and oxidation).

Decarboxylase of aromatic amino acids converts levodopa into dopamine. The main end products of this pathway are homovaniline and dihydroxyphenylacetic acid.

COMT methylates levodopa to form 3-o-methyldopa.

Decreased peripheral decarboxylation of levodopa when co-administered with benserazide results in higher plasma concentrations of levodopa and 3-o-methyldopa and lower plasma concentrations of catecholamines (dopamine, norepinephrine) and phenol carboxylic acids (homovanilic acid, dihydrophenylacetic acid).

In the intestinal mucosa and liver, benserazide is hydroxylated to form trihydroxybenzylhydrazine,which is a potent inhibitor of aromatic amino acid decarboxylase.

Excretion

Benserazide is almost completely excreted by metabolism. Metabolites are mainly in the urine - 64%, and to a lesser extent in the faeces - 24%.

Indications

Parkinson's disease, including:

patients with dysphagia with akinesia in the early morning and in the afternoon, patients with phenomena "depletion effect of a single dose" or "increase in the latent period before the onset of clinical drug effect" (125 Madopar fast tablets (dispersible));
patients with any type of levodopa steps oscillation, namely, "peak-dose dyskinesia" and "end of dose phenomenon" such as immobility during the night (Madopar REG 125).

Syndrome of restless legs:

idiopathic syndrome of restless legs;
syndrome of "restless legs" in patients with chronic renal failure who are on dialysis.

Forms of release

Capsules 100 mg + 25 mg (Madopar 125).

Tablets 200 mg + 50 mg (Madopar 250).

Quick-acting tablets (dispersible) 125.

Capsules with modified release of 100 mg + 25 mg (Madopar REG 125).

Instructions for use and dosage

Treatment should be started gradually, individually selecting the dose to achieve the optimal therapeutic effect.

Capsules Madopar 125 should be swallowed whole, without chewing.

Capsules Madopar GSS 125 should be swallowed whole, without chewing; they can not be opened before use in order to avoid the loss of the effect of the modified release of the active substance.

Madopar 250 tablets can be pulverized to facilitate swallowing.

Madopar 125 fast-acting tablets (dispersible) should be dissolved in 25-50 ml of water. The tablet completely dissolves in a few minutes with the formation of a milky white solution, which should be taken no later than 30 minutes after dissolving the tablet. Since a precipitate can form rapidly, it is recommended to mix the solution before use.

Parkinson's disease

Standard dosing regimen

Inside, not less than 30 minutes before or 1 hour after meals.

Initial therapy

At an early stage of Parkinson's disease, it is recommended to start treatment with Madopar at a dose of 62.5 mg (50 mg of levodopa + 12.5 mg of benserazide 3-4 times a day). With good tolerability, the dose should be gradually increased, depending on the patient's response.

The optimal effect is achieved, as a rule, at a daily dose containing 300-800 mg of levodopa + 75-200 mg of benserazide taken in 3 or more doses. To achieve the optimum effect, it can take from 4 to 6 weeks. Further increase in the daily dose, if necessary, should be carried out at intervals of 1 month.

Supportive therapy

The average maintenance dose is 125 mg (100 mg of levodopa + 25 mg of benserazide) Madopar 3-6 times a day. The frequency of reception (at least 3 times) during the day should be distributed so as to ensure the optimal effect. To optimize the effect, it may be necessary to replace Madopar 125 in the form of conventional capsules and Madopar 250 in the form of conventional tablets at Madopar 125 high-speed tablets (dispersible) or Madopar GCC 125.

Syndrome of "restless legs"

The drug should be taken 1 hour before bedtime, with a small amount of food. The maximum daily dose is 500 mg Madopara (400 mg levodopa + 100 mg benserazide).

Idiopathic syndrome of restless legs with disturbed sleep

It is recommended to appoint Madopar 125 capsules or Madopar 250 tablets.

The initial dose is 62.5-125 mg. If the effect is insufficient, Madopar should be increased to 250 mg (200 mg of levodopa + 50 mg of benserazide).

Idiopathic syndrome of restless legs with disturbed sleep and sleep

The initial dose is 1 capsule Madopar GSS 125 and 1 capsule Madopar 125 for 1 hour before bedtime. If the effect is insufficient, the dose of Madopar GSS 125 should be increased to 250 mg (2 capsules).

Idiopathic syndrome of "restless legs" with disturbances of falling asleep and sleep, as well as with disturbances during the day

In addition: 1 tablet is dispersible or 1 capsule Madopar 125, the maximum daily dose of Madopar is 500 mg (400 mg of levodopa and 100 mg of benserazide).

Syndrome of "restless legs" in patients with chronic renal failure receiving dialysis

The drug is prescribed in a dose of 125 mg (1 tablet dispersible or 1 capsule Madopar 125) 30 minutes before the onset of dialysis.

Dosage regimen in special cases

Parkinson's disease

Madopar can be combined with other anti-Parkinsonics. However, as the treatment continues, it may be necessary to reduce the dose of other drugs or to gradually eliminate them.

Madopar 125 high-speed tablets (dispersible) - a special dosage form for patients with dysphagia or akinesia in the early morning hours and in the afternoon orfor patients with the phenomenon of "depletion of the single dose effect" or "increasing the latent period before the clinical effect of the drug."

If during the day the patient has strong motor fluctuations (the phenomenon of "depletion of the single-dose effect", the phenomenon of "on-off"), it is recommended either a more frequent intake of correspondingly smaller single doses, or - what is more preferable - the application of Madopar GSS 125.

The transition to Madopar GSS 125 is best done from one day to another, starting with the morning dose. It should be left with the same daily dose and regimen as in the case of Madopar 125 and Madopar 250.

After 2-3 days, the dose is gradually increased by approximately 50%. Patients should be warned that their condition may temporarily worsen. Due to the peculiarities of the dosage form, Madopar GSS 125 begins to act somewhat later.

The clinical effect can be achieved more quickly by appointing Madopar GSS 125 together with Madopar 125 capsules or Madopar 125 high-speed tablets (dispersible). This may be optimal as the first morning dose, which should be slightly higher than the subsequent ones.

The dose of Madopar GSS 125 should be selected slowly and carefully, and the interval between dose changes should be at least 2-3 days.

In patients with symptoms of the disease, manifested at night, a positive effect could be achieved by gradually increasing the evening dose of Madopar GSS 125 to 250 mg (2 capsules) before bedtime.

With the expressed effect of Madopar GSS 125 (dyskinesia), it is more effective to increase the intervals between doses than to decrease the single dose.

If Madopar GSA 125 is not effective enough, then it is recommended to return to the treatment Madopar 125, Madopar 250 or Madopar 125 with high-speed tablets (dispersible) applied earlier.

With prolonged therapy, episodes of "congealing", "phenomenon of depletion" of the "on-off" phenomenon are possible. When episodes of "congealing", "phenomenon of exhaustion", the dose of the drug is crushed (a single dose is reduced or the interval between doses is reduced), and when the phenomenon of "on-off" occurs, an increase in the single dose with a decrease in the number of receptions. Subsequently, you can try again to increase the dose to enhance the effectiveness of treatment.

In patients with mild or moderate renal insufficiency, dose adjustment is not required. Madopar is well tolerated by patients receiving hemodialysis sessions.

Syndrome of "restless legs"

To avoid the increase in the symptoms of the restless legs syndrome (early appearance during the day, increased severity and involvement of other parts of the body), the daily dose should not exceed the recommended maximum dose of Madopar - 500 mg (400 mg levodopa + 100 mg benserazide).

If clinical symptoms increase, the dose of levodopa should be reduced or gradual withdrawal of levodopa and another therapy.

Side effect

agitation;
anxiety;
insomnia;
hallucinations;
rave;
temporary disorientation (especially in elderly patients and in patients with history of these symptoms);
depression;
headache;
dizziness;
spontaneous movements (such as chorea or athetosis);
episodes of "congealing";
weakening of the effect by the end of the period of the action of the dose (the phenomenon of "exhaustion");
phenomenon of "on-off";
severe drowsiness;
episodes of sudden drowsiness;
increased manifestations of the syndrome of restless legs;
nausea, vomiting;
diarrhea;
loss or change in taste;
dryness of the oral mucosa;
arrhythmias;
Orthostatic hypotension (weakening after reduction of Madopara dose);
arterial hypertension;
rhinitis;
bronchitis;
hemolytic anemia, transient leukopenia, thrombocytopenia;
itching;
rash;
increased blood urea nitrogen;
changing the color of urine to red, darkening when standing;
anorexia;
febrile infection.

Contraindications

decompensated disturbance of the functions of the organs of the endocrine system;
decompensated liver function disorder;
decompensated renal dysfunction (with the exception of patients with the syndrome of restless legs receiving dialysis);
diseases of the cardiovascular system in the stage of decompensation;
mental illness with a psychotic component;
angle-closure glaucoma;
simultaneous administration with nonselective MAO inhibitors, a combination of MAO type A and MAO type B inhibitors;
age up to 25 years;
Women of childbearing age who do not use reliable methods of contraception;
pregnancy;
lactation period (breastfeeding);
hypersensitivity to the components of the drug.

Application in pregnancy and lactation

Madopar is contraindicated in pregnancy and in women of childbearing age who do not use reliable methods of contraception, because of a possible disruption of the development of the skeleton in the fetus.

If pregnancy occurs during treatment with Madopar, the drug should be immediately discontinued in accordance with the recommendations of the attending physician.

It is not known whether benserazide is excreted in breast milk. If you need to use Madopar during lactation, breastfeeding should be discontinued, as it is impossible to exclude the development of skeletal disorders in the child.

Use in children

Contraindicated in children, adolescents and young people under the age of 25 years.

special instructions

In persons with hypersensitivity to the drug, the development of appropriate reactions is possible.

Adverse reactions from the digestive system, possible at the initial stage of treatment, are largely eliminated if you take Madopar with a small amount of food or liquid, and also with a slow increase in the dose.

Patients with open-angle glaucoma should regularly monitor intraocular pressure, as theoretically levodopa may increase intraocular pressure.

In patients taking levodopa, it is recommended to periodically monitor the blood formula, the function of the liver and kidneys.

Patients with diabetes should often monitor blood glucose levels and correct the dose of hypoglycemic drugs.

If possible, Madopar should be continued as long as possible before general anesthesia, with the exception of halothane anesthesia. Since the patient receiving Madopar during the halothane anesthesia may experience fluctuations in blood pressure and arrhythmia, Madopara should be withdrawn 12-48 hours before the surgery. After the operation, the treatment is resumed, gradually increasing the dose to the previous level.

Madopar can not be abolished abruptly. Abrupt withdrawal of the drug may lead to the development of a malignant neuroleptic syndrome (fever, muscle rigidity, as well as possible mental changes and elevated serum CK), which can take a life-threatening form. If such symptoms occur, the patient should be under the supervision of a doctor (if necessary, hospitalization) and receive appropriate symptomatic therapy, which may include the re-appointment of Madopar after an appropriate assessment of the patient's condition.

Depression can be a clinical manifestation of the underlying disease (parkinsonism, restless legs syndrome) and may also occur with Madopar therapy. Patients receiving Madopar should be carefully monitored in terms of the possible emergence of mental side effects.

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 excess of therapeutic doses of the drug.

Impact on the ability to drive vehicles and manage mechanisms

When there is drowsiness, sudden episodes of drowsiness, the patient should refuse to drive the car or work with machines and mechanisms. When these symptoms appear, you should consider reducing the dose or canceling therapy.

Drug Interactions

Pharmacokinetic interaction

With the simultaneous use of trihexyphenidyl (anticholinergic drug) reduces the rate, but not the degree of absorption of levodopa. The administration of trihexyphenidyl along with Madopar GSC 125 does not affect the pharmacokinetics of levodopa.

With simultaneous application of antacids together with Madopar GSS, the degree of absorption of levodopa is reduced by 32%.

Iron sulfate reduces Cmax in blood plasma and the value of AUC of levodopa by 30-50%; these changes in some cases are clinically significant.

Metoclopramide increases the rate of absorption of levodopa.

Levodopa does not enter into pharmacokinetic interaction with bromocriptine, amantadine, selegiline and domperidone.

Pharmacodynamic interaction

Neuroleptics, opiates and antihypertensive drugs containing reserpine inhibit the action of Madopar.

If Madopar is needed, patients receiving irreversible non-selective MAO inhibitors should undergo at least 2 weeks from the moment of discontinuation of the MAO inhibitor before starting Madopar.

Selective inhibitors of MAO type B (including selegiline, rasagiline) and selective MAO inhibitors type A (moclobemide) can be prescribed against the background of Madopar treatment. In this case, it is recommended to adjust the dose of levodopa depending on the individual patient need in terms of efficacy and tolerability. The combination of MAO type A and MAO MAO inhibitors is equivalent to the use of a non-selective MAO inhibitor, so this combination should not be administered concomitantly with Madopar.

Madopar should not be administered concurrently with sympathomimetics (epinephrine, norepinephrine, isoproterenol, amphetamine) as levodopa may potentiate their action. If simultaneous reception is still mandatory, you should carefully monitor the state of the cardiovascular system and, if necessary, reduce the dose of sympathomimetics.

Possible combined application of the drug to other antiparkinsonian drugs (anticholinergics, amantadine, dopamine agonists), while may increase not only desirable, but unwanted effects. It may be necessary to reduce the dose of Madopar or another drug.

With the simultaneous use of Madopar with an inhibitor of COMT, a dose reduction of Madopar may be required. If treatment is started Madopar, anticholinergic medication should not be stopped abruptly, as levodopa begins to act immediately.

As a patient receiving Madopar during halothane anesthesia may experience fluctuations in blood pressure and arrhythmia, taking Madopar should be discontinued for 12-48 hours prior to surgery.

Levodopa can affect the results of laboratory determination of catecholamines, creatinine, uric acid and glucose, a false positive result of Coombs test is possible.

In patients receiving Madopar, taking the drug concomitantly with protein-rich food can disrupt the absorption of levodopa from the digestive tract.

Analogues of medicinal product Madopar

Structural analogs for the active substance:

Levodopa / Benserazide Teva;
Madopar high-speed tablets (dispersible) 125;
Madopar GSS 125.

Analogues on the curative effect (agents for the treatment of Parkinson's disease):

Azilect;
Bromocriptine;
Bromergon;
Duellin;
Zimox;
Izik;
Cognitive;
Creeded;
Levodopa;
Midantan;
Mirapex;
On whom;
Neomidantan;
Niar;
Newpro;
Decrying;
Parcón;
Parlodel;
Permax;
Piribedil;
Pramipexole;
Pronoran;
Razagiline mesylate;
Rekvip Modabit;
Rolprin SR;
Segan;
Selegiline;
Sinemet;
Stalevo;
Striaton;
Tasmar;
Tremonorm;
Eldepril;
Yumeks.

If there are no analogues of the medication for the active substance, you can go to the links below for diseases, from which the corresponding drug helps, and to look at the available analogs for therapeutic effects.

Used for the treatment of diseases: Parkinson's disease, restless legs syndrome