Madopar “125” dispersible tablets 100 mg+25 mg 100 pcs.

Composition and release form

Madopar® fast-acting tablets (dispersible) “125”

in dark glass bottles 30 or 100 pcs.; 1 bottle in a cardboard pack.

Madopar® "125"

in dark glass bottles 30 or 100 pcs.; 1 bottle in a cardboard pack.

Madopar® “250”

in dark glass bottles 30 or 100 pcs.; 1 bottle in a cardboard pack.

Madopar® GSS "125"

in dark glass bottles 30 or 100 pcs.; 1 bottle in a cardboard pack.

Madopar 125, 100 mg+25 mg, capsules, 100 pcs.

Inside,

at least 30 minutes before or 1 hour after meals.

Capsules (Madopar® “125” or Madopar® GSS “125”) should be swallowed whole without chewing. Madopar® GSS “125” capsules cannot be opened before use, otherwise the effect of the modified release of the active substance is lost.

Tablets (Madopar® 250) can be crushed to make them easier to swallow.

Dispersible tablets (Madopar® fast-acting tablets (dispersible) “125”) should be dissolved in 1/4 cup of water (25–50 ml); The tablet dissolves completely after a few minutes to form a milky-white suspension, which should be taken no later than 30 minutes after the tablet has dissolved. Since a precipitate can quickly form, it is recommended to stir the solution before use.

Parkinson's disease

Standard dosage regimen

Treatment should be started gradually, with individual doses adjusted until the optimal effect is achieved.

Initial therapy

At the early stage of Parkinson's disease, it is recommended to start treatment with Madopar® with 62.5 mg (50 mg levodopa + 12.5 mg benserazide) 3-4 times a day. If the initial dosing schedule is tolerated, the dose should be increased slowly based on patient response.

The optimal effect is usually achieved with a daily dose of 300–800 mg levodopa + 75–200 mg benserazide, taken in 3 or more divided doses. It may take 4 to 6 weeks to achieve optimal effect. If it is necessary to further increase the daily dose, this should be done at intervals of 1 month.

Maintenance treatment

The average maintenance dose is 125 mg (100 mg levodopa + 25 mg benserazide) 3-6 times a day. The number of doses (at least 3) and their distribution throughout the day should ensure optimal effect.

To optimize the effect, you can replace Madopar® “125” capsules and Madopar® “250” tablets with Madopar® fast-acting tablets (dispersible) or Madopar® GSS “125” capsules.

Restless legs syndrome

The maximum permissible dose is 500 mg/day Madopar® (400 mg levodopa + 100 mg benserazide). 1 hour before bedtime, with a small amount of food.

Idiopathic restless legs syndrome with sleep disturbances

It is recommended to prescribe Madopar® “125” capsules or Madopar® “250” tablets.

Initial dose:

62.5 mg (50 mg levodopa + 12.5 mg benserazide)–125 mg (100 mg levodopa + 25 mg benserazide) Madopar®. If the effect is insufficient, the dose should be increased to 250 mg (200 mg levodopa + 50 mg benserazide) Madopar®.

Idiopathic restless legs syndrome with sleep and sleep disorders

Initial dose:

1 caps. Madopar® GSS “125” and 1 caps. Madopar® “125” 1 hour before bedtime. If the effect is insufficient, it is recommended to increase the dose of Madopar® GSS “125” to 250 mg (2 capsules).

Idiopathic restless legs syndrome with difficulty falling asleep and staying asleep, as well as disturbances during the day

Additionally:

1 table dispersible or 1 cap. Madopar® "125", the maximum permissible daily dose is 500 mg (400 mg levodopa + 100 mg benserazide).

Restless legs syndrome in patients with chronic renal failure receiving dialysis

125 mg Madopar® (1 dispersible tablet or 1 capsule Madopar® “125”) 30 minutes before the start of dialysis.

Dosing in special cases

Parkinson's disease

Madopar® can be combined with other antiparkinsonian drugs; as treatment continues, it may be necessary to reduce the dose of other drugs or gradually discontinue them.

Madopar® fast-acting tablets (dispersible) “125” is a special dosage form for patients with dysphagia or akinesia in the early morning and afternoon, or with the phenomena of “depletion of the effect of a single dose” or “increase in the latent period before the onset of the clinical effect of the drug” .

If during the day the patient experiences pronounced motor fluctuations (the phenomenon of “exhaustion of the effect of a single dose”, the phenomenon of “on-off”), it is recommended either more frequent administration of correspondingly smaller single doses, or, which is preferable, the use of Madopar® GSS “125”.

It is best to start the transition to Madopar® GSS "125" with the morning dose, maintaining the daily dose and dosage regimen of Madopar® "125" or Madopar® "250".

After 2–3 days, the dose is gradually increased by approximately 50%. The patient should be warned that his condition may temporarily worsen. Due to its pharmacological properties, Madopar® GSS “125” begins to act somewhat later. The clinical effect can be achieved faster by prescribing Madopar® GSS “125” together with Madopar® “125” capsules or dispersible tablets. This may be especially useful in the case of the first morning dose, which should be slightly higher than subsequent doses. The individual dose of Madopar® GSS “125” should be adjusted slowly and carefully, and the interval between dose changes should be at least 2–3 days.

In patients with nocturnal symptoms, a positive effect was achieved by gradually increasing the evening dose of Madopar® GSS “125” to 250 mg (2 capsules) before going to bed.

To eliminate the pronounced effect of Madopar® GSS “125” (dyskinesia), increasing the intervals between doses is more effective than reducing the single dose.

If Madopar® GSS "125" is not effective enough even at a daily dose corresponding to 1500 mg of levodopa, it is recommended to return to the previous treatment with Madopar® "125", Madopar® "250" and Madopar® fast-acting tablets (dispersible) "125".

No dose adjustment is required in patients with mild or moderate renal impairment.

Madopar® is well tolerated by patients receiving hemodialysis sessions.

With long-term therapy, episodes of “freezing”, “exhaustion phenomenon”, and “on-off” phenomena may occur. During episodes of “freezing” and the “exhaustion phenomenon,” they resort to splitting the dose of the drug (reducing the single dose or shortening the interval between doses of the drug), and when the “on-off” phenomenon occurs, increasing the single dose while reducing the number of doses. Subsequently, you can try to increase the dose again to enhance the effect of treatment.

Restless legs syndrome

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

If clinical symptoms increase, the dose of levodopa should be reduced or levodopa should be gradually discontinued and other therapy should be prescribed.

Description of the dosage form

Dispersible tablets: cylindrical, flat on both sides with a beveled edge, white or almost white, odorless or slightly odorless, slightly marbled, engraved “ROCHE 125” on one side of the tablet and a break line on the other side. Tablet diameter is about 11 mm; thickness - about 4.2 mm.

Capsules: hard gelatin; body - pinkish-flesh color, opaque; the lid is light blue, opaque; The capsule is marked “ROCHE” in black. The contents of the capsules are a fine granular powder, sometimes clumped, light beige in color, with a subtle odor.

Tablets: cylindrical, flat with a beveled edge, pale red in color with small inclusions, with a subtle odor; on one side of the tablet there is a cross-shaped line, engraving “ROCHE” and a hexagon; on the other there is a cross-shaped risk. Tablet diameter - 12.6–13.4 mm; thickness - 3–4 mm.

Modified release capsules: hard gelatin; body - light blue, opaque; the lid is dark green, opaque; The capsule is marked “ROCHE” in rusty red ink. The contents of the capsules are a fine granular powder, sometimes clumped, white or slightly yellowish in color, with a subtle odor.

Pharmacodynamics

Combined drug for the treatment of Parkinson's disease and restless legs syndrome.

Parkinson's disease. Dopamine, a neurotransmitter in the brain, is produced in insufficient quantities in the basal ganglia of patients with parkinsonism. Levodopa or L-DOPA (3,4-dihydrophenylalanine) is a metabolic precursor to dopamine. Unlike dopamine, levodopa penetrates well through the BBB. After levodopa enters the central nervous system, it is converted to dopamine by aromatic amino acid decarboxylase.

Replacement therapy is carried out by prescribing levodopa, the immediate metabolic precursor of dopamine, since the latter does not penetrate the BBB well.

Following oral administration, levodopa is rapidly decarboxylated to dopamine in both cerebral and extracerebral tissues. As a result, most of the administered levodopa does not reach the basal ganglia, and peripheral dopamine often causes side effects. Therefore, blocking extracerebral decarboxylation of levodopa is necessary. This is achieved by the simultaneous administration of levodopa and benserazide, a peripheral decarboxylase inhibitor.

Madopar® is a combination of these substances in an optimal ratio of 4:1 and is as effective as large doses of levodopa.

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

Dopaminergic drugs (madopar) in the correction of muscle tone in neurological diseases

In the clinical practice of a neurologist in the context of the treatment of various neurological diseases, there is often a need to correct pathologically altered muscle tone. Especially many problems in this regard have to be solved when treating patients with dystonic hyperkinesis. Dystonia is a clinical syndrome characterized by irregular slow violent movements in various parts of the body, a peculiar change in muscle tone and the formation of pathological postures [1]. This syndrome is largely heterogeneous, both clinically and in terms of the pathogenesis of its occurrence. According to prevalence, generalized, multifocal, and focal forms are distinguished; according to the form of hyperkinesis - tonic and clonic [1]. Currently, most researchers suggest that cholinergic, dopaminergic, and GABAergic (g-aminobutyric acid) brain systems are involved in the formation of this pathology [2, 3]. Accordingly, it makes sense to influence these neurotransmitter systems. Moreover, it is known that the clinical symptoms of some types of dystonic hyperkinesis regress when treated with levodopa. This primarily concerns the rigid form of torsion dystonia, also known as Segawa’s disease [4], or DOPA-dependent dystonia. This pathology has been quite well studied; it is based on genetic defects (at least three main defects are currently known, one of which is inherited in an autosomal dominant manner with incomplete penetrance, and two - in an autosomal recessive manner), as a result of which the synthesis of dopamine enzymes is disrupted. exchange and, accordingly, the synthesis of dopamine itself. The only pathogenetically justified medical intervention in this case is the prescription of levodopa drugs, and they almost completely eliminate the symptoms of the disease [1, 4]. However, in real clinical practice, as our experience shows, the correct diagnosis is rarely made, which is due to the low awareness of neurologists about this problem. A considerable proportion of cases of DOPA-dependent dystonia occur in childhood, and it is often classified as a manifestation of cerebral palsy (CP). Accordingly, the patient is prescribed all kinds of treatment and rehabilitation methods that have a minimal transient effect. In fact, a patient with an incorrect diagnosis of cerebral palsy, the hyperkinetic form, is doomed to disability, except in cases where levodopa drugs are used in the treatment of this pathology.

The Center for Neurology and Neurorehabilitation (Krasnoyarsk) operates an extrapyramidal pathology service, specializing in providing assistance to patients of this profile. Significant experience in managing patients with dystonia has been accumulated here. Analysis of this experience made it possible to develop the most effective and rational algorithms for treating patients in practical healthcare settings. The most important step in patient management is establishing the correct diagnosis.

With a typical picture of rigid torsion dystonia, diagnosis does not cause great difficulties. Therapy, based on pathogenesis, involves the use of levodopa drugs for replacement purposes. We use the well-proven drug madopar, containing levodopa and the DOPA decarboxylase inhibitor benserazide, at a dose of 125 mg 2-3 times a day.

However, much more often certain diagnostic difficulties arise due to vague clinical symptoms and late onset of the disease. The ideal solution would be to prescribe genetic testing to all patients who are likely to be diagnosed with rigid DOPA-dependent dystonia. Unfortunately, conducting this study in most patients is impossible for organizational and technical reasons. It seems reasonable to us to use a simpler diagnostic technique: we are talking about a trial prescription of the drug levodopa. Directly during the appointment, including outpatient, the patient takes a tablet of instant madopar 125 mg dissolved in 50–100 ml of water. After 30–60 minutes, changes in the state of muscle tone and other manifestations of the disease are assessed. This technique has found wide application in our work with patients who are suspected of developing parkinsonism. In DOPA-dependent dystonia, we also observed a significant effect with a pronounced regression of symptoms.

For focal and multifocal, as well as DOPA-resistant forms of dystonia, the most effective, according to modern ideas, is the use of injections of botulinum toxin, which disrupts neuromuscular impulse transmission and, accordingly, relaxes the muscles involved in the pathological process. This effect is variable in duration of action; on average, its duration lasts up to 4–5 months [5]. We completely agree with this approach, however, there are a number of nuances that should be discussed in more detail.

The administration of botulinum toxin (our clinic uses the drug Dysport) turned out to be very, very effective. But from an economic point of view, this type of treatment has its drawbacks, as it is expensive and not always available to persons who do not belong to the preferential category of patients. In addition, the duration of the effect varies between patients, and a significant aspect of the problem is the prolongation of this effect. Based on these goals, we attempted to combine Dysport injections and tablet drugs of other pharmacological groups. The best effect, from our point of view, is observed when using benzodiazepines (clonazepam) at a dose of 2–3 mg per day or anticholinergics (cyclodol) at a dose of 4–6 mg per day. In some cases, the clinical effect of the injection could be monitored for 8–18 months.

Another important reason that determines the legitimacy of prescribing combination therapy with dysport and muscle relaxants is the multifocality of dystonic hyperkinesis. Prescribing a dose of botulinum toxin to a patient that can relieve all manifestations of dystonic syndrome is impossible and simply dangerous: this drug is used only in cases where the most disabling manifestations of the disease occur, and for other symptoms the emphasis is on other drugs. In this regard, our following observation seems appropriate: in many cases of dystonic hyperkinesis with a predominance of the tonic component (primarily with cervical dystonia), we carried out the test described above with instant madopar. At the same time, the effect of weakening dystonia was sometimes noted, which made it possible to use madopar for the same purposes in the future daily at a dose of 125 mg 2-3 times a day. At the same time, a positive effect was observed. Unfortunately, after a few months (on average 6–11) this effect was significantly weakened, which does not allow these types of dystonia to be classified as the classic DOPA-dependent ones described above. However, a certain pathogenetic commonality and the involvement of dopaminergic structures occur in this case.

Thus, in our opinion, in case of dystonic syndrome with a predominant tonic (rigid) component, a test with instant madopar should be used in all cases. If there are positive results, the prescription of levodopa therapy is indicated, with careful dynamic monitoring of the patient, and if the therapy is insufficiently effective, after 1–2 months, additional use of botulinum toxin preparations is indicated.

With regard to the correction of DOPA-resistant (primary, secondary) dystonia, as well as most focal, predominantly clonic variants of the disease, the drug of choice is botulinum toxin, to enhance and prolong the effect of which it is advisable to additionally prescribe benzodiazepines and anticholinergics.

Another problem that requires an adequate solution is increased muscle tone in patients who have suffered acute cerebrovascular accident. Muscle hypertonicity significantly impairs the process of restoration of impaired motor functions, and kinesiotherapy, carried out as part of complex neurorehabilitation, sometimes turns out to be simply ineffective. Our experience has allowed us to formulate successful, from our point of view, approaches to this problem.

An increase in muscle tone during central paresis is due to the disinhibition of spinal neurons in the absence of the inhibitory influence of the cortex, which leads to the formation of spastic (pyramidal) hypertonicity. However, since the extrapyramidal system also plays a significant role in the regulation of muscle tone, its damage, as well as damage to the pyramidal tracts, leads to muscle hypertension of the extrapyramidal (plastic) type [6, 7]. Of course, in practice, both components are involved in the process in one way or another, although, as a rule, the leading one can be traced. Thus, it is advisable to divide the increase in muscle tone with central paresis into predominantly pyramidal, predominantly extrapyramidal and mixed - when it is impossible to clearly determine the leading component.

With the leading pyramidal component, the doctor has fairly well-developed treatment regimens in his arsenal, including the use of muscle relaxants, the prescription of physiotherapeutic procedures, and, if necessary, massage and acupuncture [6, 7].

Treatment of muscle hypertension through injections of botulinum toxin seems promising to us, but to date we have not accumulated sufficient personal experience with this method, which is associated with economic and technical difficulties.

During treatment, we actively use drugs with different mechanisms of action. The most commonly used is tizanidine (Sirdalud), a centrally acting muscle relaxant that stimulates presynaptic α2-adrenergic receptors, suppressing the release of excitatory amino acids that activate N-methyl-D-aspartate receptors (NMDA receptors). Tizanidine, in our opinion, is one of the most effective drugs in this group. Average therapeutic doses range from 4 to 12 mg per day. The most common side effect that occurs when taking the drug and in some cases interferes with its use is the hypotensive effect.

Tolperisone hydrochloride (Mydocalm) is another centrally acting muscle relaxant that is actively used in our clinic. The mechanism of action of the drug is associated with an inhibitory effect on the caudal part of the reticular formation and central n-cholinolytic properties. The average effective dose is 225–450 mg per day. The drug, in our opinion, is somewhat less effective, but is well tolerated by patients.

Also, in some cases, we resort to prescribing baclofen, a centrally acting muscle relaxant, a derivative of γ-aminobutyric acid, and a GABA β-receptor agonist. The rather rare use of this drug to reduce muscle tone in central paresis is due to significant problems that arise when titrating its dose (starting from 5 mg 3 times a day and ending with 25 mg 3 times a day), since it is capable of, along with a positive effect in the form of reduction spasticity leads to severe muscle weakness, which prevents kinesiotherapy and ergotherapy. In addition, a sharp increase in dose (as well as abrupt withdrawal) can provoke the development of convulsive and psychotic reactions, which also limits the use of this drug. However, it finds use when other drugs are ineffective, primarily in spinal patients with a gross increase in muscle tone.

Drugs of the benzodiazepine group (primarily clonazepam) lead to a pronounced sedative effect, often provoke or aggravate cognitive and vestibular disorders, and therefore in our practice they are not used to reduce muscle tone in post-stroke patients.

Noteworthy is the fact that in patients with increased muscle tone of a mixed or predominantly extrapyramidal type, the effectiveness of traditional muscle relaxants is insignificant. Among patients at our Center who have suffered a stroke, the number of such cases ranges from 12 to 18%. Based on the presence of plastic tone, as well as minimal elements of extrapyramidal insufficiency (mild hypomimia, bradyphrenia), an attempt was made to use small doses of DOPA-containing drugs for such patients. At the first stage of working with the patient (after establishing the presence of excess tone, increased by mixed or plastic type), a test was carried out with instant madopar. If there was a positive effect, the drug madopar was prescribed at a dose of 62.5 ± 125 mg daily, and against this background, muscle tone decreased and rehabilitation exercises were facilitated. Just like other muscle relaxants, madopar is prescribed in long courses. Therapy continues not only during the inpatient neurorehabilitation course, but also at the stage of outpatient follow-up treatment for 2–3 months, and, if necessary, longer. We would especially like to emphasize that in this case we are not talking about vascular parkinsonism (which in the classical version has a completely different clinical picture - with a predominant involvement of the lower body and cannot be treated with DOPA-containing drugs), but about central hemiparesis syndrome with a combined disorder of muscle tone at various stages of stroke.

Thus, we consider it rational to conduct a test with instant madopar in patients after a stroke who have in their neurological status, in addition to the leading syndrome of central hemiparesis, signs of extrapyramidal insufficiency with impaired muscle tone of a plastic or mixed type, as well as in patients resistant to traditional muscle relaxants . In case of a positive effect, it seems to us advisable to prescribe madopar in order to reduce muscle tone in this category of patients.

Literature

1. Markova E. D. Dystonic hyperkinesis: phenomenology, classification, generalized forms // Extrapyramidal disorders: a guide to diagnosis and treatment / ed. V. N. Shtoka et al. M.: MEDpress-inform, 2002. P. 282–291.
2. Golubev V.L. Focal and segmental forms of dystonia//Extrapyramidal disorders: a guide to diagnosis and treatment/ed. V. N. Shtoka et al. M.: MEDpress-inform, 2002. P. 291–302.
3. Barkhatova V.P., Markova E.D. Issues of pathogenesis and treatment of torsion dystonia // Journal of neuropathology and psychiatry. 1978. T. 78. No. 3. P. 1121–1128.
4. Segawa M., Ohmi K., Itoh S. et al. Childhood basal ganglia disease with remarkable response to L-dopa, “hereditary basal ganglia disease with marked diurnal fluctuation//Chiryo. 1972; 24:667–672.
5. Timerbaeva L. A., Ivanova-Smolenskaya I. A., Markova E. D., Levin O. S. Treatment of extrapyramidal disorders with botulinum toxin / Extrapyramidal disorders: a guide to diagnosis and treatment / ed. V. N. Shtoka et al. M.: MEDpress-inform, 2002, pp. 567–577.
6. Vorobyova O. V. Impaired muscle tone in the post-stroke period: issues of therapy // Consilium Medicum. 2004. T. 6. No. 12.
7. Parfenov V. A. Botox in the treatment of spasticity//Treatment of nervous diseases. 2001. T. 2. No. 2.
8. Kamchatnov P.R. Spasticity - modern approaches to therapy // Russian Medical Journal. 2004. No. 14. T. 12. P. 848–853.

D. V. Pokhabov , Candidate of Medical Sciences, Associate Professor S. V. Prokopenko, Doctor of Medical Sciences, Professor V. G. Abramov E. M. Arakchaa Krasnoyarsk State Medical Academy, Center for Neurology and Neurorehabilitation, Krasnoyarsk

Pharmacokinetics

Suction

Madopar® “125” capsules and Madopar® “250” tablets

Levodopa is primarily absorbed in the upper small intestine. The time to reach Cmax of levodopa is 1 hour after taking capsules or tablets.

Capsules and tablets are bioequivalent.

Cmax of levodopa in plasma and the extent of levodopa absorption (AUC) increase proportionally to the dose (in the levodopa dose range from 50 to 200 mg).

Eating reduces the rate and extent of absorption of levodopa. When capsules or tablets are administered after meals, the Cmax of levodopa in plasma is reduced by 30% and is achieved later. The degree of absorption of levodopa is reduced by 15%. The absolute bioavailability of levodopa in Madopar® “125” capsules and Madopar® “250” tablets is 98% (from 74 to 112%).

Madopar® fast-acting tablets (dispersible) “125”

The pharmacokinetic profiles of levodopa after administration of dispersible tablets are similar to those after administration of Madopar® "125" capsules or Madopar® "250" tablets, but the time to reach Cmax tends to decrease. Patient absorption of dispersible tablets is less variable.

Madopar® GSS "125", capsules with modified release of the active substance

Madopar® GSS “125” has different pharmacokinetic properties than the above release forms. The active substances are released slowly in the stomach. Cmax in plasma is 20–30% less than that of conventional dosage forms and is achieved 3 hours after administration. The dynamics of plasma concentration is characterized by a longer half-life (the period of time during which the plasma concentration is greater than or equal to half the maximum) than that of Madopar® 125 capsules and Madopar® 250 tablets, which indicates a continuous modifiable release . The bioavailability of Madopar® GSS “125” is 50–70% of the bioavailability of Madopar® “125” capsules and Madopar® “250” tablets and does not depend on food intake. Food intake does not affect the Cmax of levodopa, which is achieved later, 5 hours after taking Madopar® GSS “125”.

Distribution

Levodopa crosses the BBB via a saturable transport system. It does not bind to plasma proteins. Distribution volume - 57 l. The AUC for levodopa in cerebrospinal fluid is 12% of that in plasma.

Benserazide 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 main pathways (decarboxylation and o-methylation) and two additional pathways (transamination and oxidation).

Aromatic amino acid decarboxylase converts levodopa to dopamine. The main end products of this metabolic pathway are homovanillic and dihydroxyphenylacetic acids.

Catechol-o-methyl-transferase methylates levodopa to form 3-o-methyldopa. The half-life of this main metabolite from plasma is 15–17 hours, and its accumulation occurs in patients taking therapeutic doses of Madopar®.

Reduced peripheral decarboxylation of levodopa when coadministered with benserazide leads to higher plasma concentrations of levodopa and 3-o-methyldopa and lower plasma concentrations of catecholamines (dopamine, norepinephrine) and phenolcarboxylic acids (homovanillic acid, dihydrophenylacetic acid).

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

Removal

With peripheral inhibition of T1/2 decarboxylase, levodopa - 1.5 hours. Plasma clearance of levodopa is approximately 430 ml/min.

Benserazide is almost completely eliminated by metabolism. Metabolites are excreted mainly in urine (64%) and to a lesser extent in feces (24%).

Pharmacokinetics in special groups of patients

Patients with renal and liver failure. There are no data on the pharmacokinetics of levodopa in patients with renal and hepatic impairment.

Elderly patients (65–78 years). In elderly patients (65–78 years) with Parkinson's disease, T1/2 and AUC of levodopa increase by 25%, which is not a clinically significant change and does not in any way affect the dosage regimen.

Instructions for use of MADOPAR

Treatment should be started gradually, with individual doses adjusted until the optimal therapeutic effect is achieved. The following dosage regimen instructions should be considered as general recommendations.

Madopar 125 mg capsules should be swallowed whole without chewing. Madopar 250 mg tablets can be crushed to make them easier to swallow. Madopar GSS capsules should not be opened before use, otherwise the effect of the modified release of the active substance is lost.

Standard dosage regimen

Parksinson's disease

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

Initial treatment.

At the early stage of Parkinson's disease, it is recommended to begin treatment with Madopar at a dose containing 50 mg of levodopa + 12.5 mg of benserazide 3-4 times a day. If well tolerated, the dose should be gradually increased, depending on the patient's response.

The optimal effect is achieved, as a rule, with a daily dose containing 300-800 mg of levodopa + 75-200 mg of benserazide, in 3 or more doses. It may take 4 to 6 weeks to achieve optimal results. Further increases in the daily dose, if necessary, should be carried out at intervals of 1 month.

Maintenance treatment.

The average maintenance dose is 125 mg (100 mg levodopa + 25 mg benserazide) 3-6 times a day. The frequency of administration (at least 3 times) during the day should be distributed so as to ensure optimal effect.

To optimize the effect, you can replace Madopar capsules 125 mg and tablets 250 mg with Madopar GSS.

Restless legs syndrome

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

Idiopathic restless legs syndrome with sleep disturbances

It is recommended to prescribe Madopar in the form of 125 mg capsules or 250 mg tablets.

The initial dose of Madopar is 62.5 mg (50 mg levodopa + 12.5 mg benserazide) - 125 mg (100 mg levodopa + 25 mg benserazide). If the effect is insufficient, the dose of Madopar should be increased to 250 mg (200 mg levodopa + 50 mg benserazide).

Idiopathic restless legs syndrome with sleep and sleep disorders

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

Idiopathic restless legs syndrome with difficulty falling asleep and staying asleep, as well as disturbances during the day

Additionally:

• Madopar 1 capsule 125 mg, the maximum daily dose of Madopar is 500 mg (400 mg levodopa and 100 mg benserazide).

Restless legs syndrome in patients with chronic renal failure receiving dialysis

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

Dosage regimen in special cases

Parkinson's disease

Madopar can be combined with other antiparkinsonian drugs; as treatment continues, it may be necessary to reduce the dose of other drugs or gradually discontinue them.

It is better to start the transition to Madopar GSS with a morning dose, maintaining the daily dose and regimen of Madopar in the form of 125 mg capsules or 250 mg tablets.

After 2-3 days, the dose is gradually increased by approximately 50%. The patient should be warned that his condition may temporarily worsen. Due to its pharmacokinetic properties, Madopar GSS begins to act somewhat later. The clinical effect can be achieved faster by prescribing Madopar GSS together with Madopar in the form of capsules 125 mg. This may be especially useful in the case of the first morning dose, which should be slightly higher than subsequent doses. The individual dose of Madopar GSS should be selected slowly and carefully, the interval between dose changes should be at least 2-3 days. In patients with nocturnal symptoms, a positive effect was achieved by gradually increasing the evening dose of Madopar GSS to 250 mg (2 capsules) before bedtime.

To eliminate the pronounced effect of Madopar GSS (dyskinesia), increasing the intervals between doses is more effective than reducing the single dose. If Madopar GSS is not effective enough, it is recommended to return to previous treatment with Madopar in the form of 125 mg capsules and 250 mg tablets.

In patients with mild or moderate renal impairment

no dose adjustment is required.

Madopar is well tolerated by patients receiving hemodialysis sessions. With long-term therapy, episodes of “freezing”, “dose depletion phenomenon”, and “on-off” phenomena may occur. During episodes of “freezing” and the “dose depletion phenomenon,” they resort to splitting the dose of the drug (reducing the single dose or shortening the interval between doses of the drug), and when the “on-off” phenomenon occurs, they increase the single dose while reducing the number of doses. Then you can try to increase the dose again to enhance the effect of treatment.

Restless legs syndrome

To avoid an increase in the symptoms of restless legs syndrome (early appearance during the day, increasing severity and involvement of other parts of the body), you 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 levodopa should be gradually discontinued and other therapy should be prescribed.

Indications of the drug Madopar® “125”

Parkinson's disease:

— Madopar® fast-acting tablets (dispersible) “125” — a special dosage form for patients with dysphagia and akinesia in the early morning hours and in the afternoon, or with the phenomena of “depletion of the effect of a single dose” or “increase in the latent period before the onset of the clinical effect of the drug ";

— Madopar® GSS “125” is indicated for any type of fluctuation in the effect of levodopa (namely: “peak dose dyskinesia” and “end dose phenomenon”, for example, immobility at night);

restless legs syndrome, including idiopathic and restless legs syndrome in patients with chronic renal failure on dialysis.

Madopar® gss "125" (Madopar® hbs "125")

Treatment should be started gradually, with individual doses adjusted until the optimal therapeutic effect is achieved.

Madopar® 125 capsules should be swallowed whole without chewing.

Madopar® GSS “125” capsules should be swallowed whole without chewing; they should not be opened before use to avoid loss of the modified release effect of the active substance.

Madopar® 250 tablets can be crushed to make them easier to swallow.

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

Parkinson's disease

Standard dosage regimen

Orally, at least 30 minutes before or 1 hour after meals.

Initial therapy

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

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

Maintenance therapy

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

Restless legs syndrome

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

Idiopathic restless legs syndrome with sleep disturbances

It is recommended to prescribe Madopar® “125” capsules or Madopar® “250” tablets.

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

Idiopathic restless legs syndrome with sleep and sleep disorders

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

Idiopathic restless legs syndrome with difficulty falling asleep and staying asleep, as well as disturbances during the day

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

Restless legs syndrome in patients with chronic renal failure receiving dialysis

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

Dosage regimen in special cases

Parkinson's disease

Madopar® can be combined with other antiparkinsonian drugs. However, as treatment continues, it may be necessary to reduce the dose of other drugs or gradually discontinue them.

Madopar® "125" fast-acting tablets (dispersible) - a special dosage form for patients with dysphagia or akinesia in the early morning and afternoon or for patients with the phenomenon of "depletion of the effect of a single dose" or "increasing the latency period before the onset of clinical effect of the drug "

If during the day the patient experiences strong motor fluctuations (the phenomenon of “exhaustion of the effect of a single dose”, the phenomenon of “on-off”), it is recommended either more frequent administration of correspondingly smaller single doses, or, which is preferable, the use of Madopar GSS “125”.

It is best to switch to Madopar® GSS “125” from one day to the next, starting with the morning dose. You should keep the same daily dose and dosage regimen as when taking 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 characteristics of the dosage form, Madopar® GSS “125” begins to act somewhat later.

The clinical effect can be achieved faster by prescribing Madopar® GSS “125” together with Madopar® “125” capsules or Madopar “125” fast-acting tablets (dispersible). This may be optimal as the first morning dose, which should be slightly higher than subsequent doses.

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

In patients with symptoms of the disease that manifest themselves at night, a positive effect was achieved by gradually increasing the evening dose of Madopar GSS “125” to 250 mg (2 capsules) before bedtime.

If the effect of Madopar GSS “125” (dyskinesia) is pronounced, increasing the intervals between doses is more effective than reducing the single dose.

If Madopar® GSS "125" is not effective enough, it is recommended to return to the previously used treatment with Madopar "125", Madopar "250" or Madopar "125" fast-acting tablets (dispersible).

With long-term therapy, episodes of “freezing”, “exhaustion phenomenon” and the “on-off” phenomenon may occur. In case of episodes of “freezing”, “exhaustion phenomenon”, the dose of the drug is divided (reducing the single dose or shortening the interval between doses of the drug), and when the “on-off” phenomenon occurs, the single dose is increased with a decrease in the number of doses. Subsequently, you can try to increase the dose again to enhance the effectiveness of treatment.

In patients with mild or moderate renal impairment

no dose adjustment is required.
Madopar® is well tolerated by patients receiving hemodialysis sessions
.

Restless legs syndrome

To avoid an increase in the symptoms of restless legs syndrome (early appearance during the day, increasing 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 levodopa should be gradually discontinued and other therapy should be prescribed.

Contraindications

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

decompensated dysfunction of endocrine organs, liver or kidneys (except for patients with restless legs syndrome receiving dialysis);

diseases of the cardiovascular system in the stage of decompensation;

mental illness with a psychotic component;

angle-closure glaucoma;

in combination with non-selective MAO inhibitors or a combination of MAO-A and MAO-B inhibitors;

age under 25 years;

pregnancy;

breastfeeding period;

women of childbearing age who are not using reliable methods of contraception (see “Pregnancy and lactation”).

Use during pregnancy and breastfeeding

Madopar® is absolutely contraindicated during pregnancy and in women of childbearing age who do not use reliable methods of contraception, due to possible disruption of skeletal development in the fetus.

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

If it is necessary to take Madopar® during breastfeeding, breastfeeding should be discontinued due to the lack of reliable data on the penetration of benserazide into breast milk. The risk of abnormal skeletal development in a newborn cannot be ruled out.

Side effects

From the blood system: rare cases of hemolytic anemia, transient leukopenia, thrombocytopenia. In patients taking levodopa for a long time, it is recommended to periodically monitor the blood count, liver and kidney function.

From the gastrointestinal tract: anorexia, nausea, vomiting, diarrhea, isolated cases of loss or change in taste, dryness of the oral mucosa.

On the skin: rarely - itching, rash.

From the cardiovascular system: arrhythmias, orthostatic hypotension (weakens after reducing the dose of Madopar®), arterial hypertension.

From the nervous system and mental sphere: agitation, anxiety, insomnia, hallucinations, delirium, temporary disorientation (especially in elderly patients and patients with a history of these symptoms), depression, headache, dizziness, sometimes in later stages of treatment - spontaneous movements (such as chorea or athetosis), episodes of “freezing”, weakening of the effect towards the end of the dose period (the “exhaustion” phenomenon), the “on-off” phenomenon, severe drowsiness, episodes of sudden drowsiness, increased manifestations of restless legs syndrome .

From the body as a whole: febrile infection, rhinitis, bronchitis.

Laboratory indicators: sometimes - a transient increase in the activity of liver transaminases and alkaline phosphatase, an increase in blood urea nitrogen, a change in the color of urine to red, darkening when standing.

Madopar GSS Capsules, 100 pcs, 100 + 25 mg + mg, modified release

Directions for use and doses

Capsules (Madopar “125” or Madopar GSS “125”) should be swallowed whole without chewing. Madopar GSS “125” capsules cannot be opened before use, otherwise the effect of the modified release of the active substance is lost. Tablets (Madopar "250") can be crushed to make swallowing easier. Dispersible tablets (Madopar fast-acting tablets /dispersible/ “125”) should be dissolved in a quarter glass of water (25-50 ml); The tablet dissolves completely after a few minutes to form a milky-white suspension, which should be taken no later than half an hour after the tablet has dissolved. Since a precipitate can quickly form, it is recommended to stir the solution before use. Parkinson's disease Orally, at least 30 minutes before or 1 hour after meals. Standard dosage regimen Treatment should be started gradually, individually selecting doses to achieve optimal effect. Initial therapy At the early stage of Parkinson's disease, it is recommended to begin treatment with Madopar by taking 62.5 mg (50 mg levodopa + 12.5 mg benserazide) 3-4 times a day. If the initial dosing schedule is tolerated, the dose should be increased slowly based on patient response. The optimal effect is usually achieved with a daily dose of 300-800 mg levodopa + 75-200 mg benserazide, taken in three or more divided doses. It may take 4 to 6 weeks to achieve optimal results. If it is necessary to further increase the daily dose, this should be done at intervals of 1 month. Maintenance therapy The average maintenance dose is 125 mg (100 mg levodopa + 25 mg benserazide) 3-6 times a day. The number of doses (at least three) and their distribution throughout the day should ensure optimal effect. To optimize the effect, you can replace Madopar “125” capsules and Madopar “250” tablets with Madopar fast-acting tablets /dispersible/ “125” or Madopar GSS “125” capsules. Restless legs syndrome The maximum permissible dose per day is 500 mg of Madopar (400 mg of levodopa + 100 mg of benserazide). 1 hour before bedtime with a small amount of food. Before using Madopar, you should refrain from eating foods rich in protein. Idiopathic restless legs syndrome with sleep disturbances It is recommended to prescribe Madopar “125” capsules or Madopar “250” tablets. Initial dose: 62.5 mg (50 mg levodopa + 12.5 mg benserazide) - 125 mg (100 mg levodopa + 25 mg benserazide) Madopara. If the effect is insufficient, the dose should be increased to 250 mg (200 mg levodopa + 50 mg benserazide) of Madopar. Idiopathic restless legs syndrome with sleep and sleep disorders Initial dose: 1 capsule of Madopar GSS “125” and 1 capsule of Madopar “125” 1 hour before bedtime. If the effect is insufficient, it is recommended to increase the dose of Madopar GSS “125” to 250 mg (2 capsules). Idiopathic restless legs syndrome with sleep and sleep disturbances, as well as disturbances during the dayAdditionally: 1 dispersible tablet or 1 capsule Madopar “125”, the maximum permissible daily dose is 500 mg (400 mg levodopa + 100 mg benserazide) Madopar. “Restless legs” syndrome in patients with chronic renal failure receiving dialysis 125 mg Madopar (1 dispersible tablet or 1 capsule Madopar “125”) 30 minutes before the start of dialysis. Dosing in special cases Parkinson's disease Madopar can be combined with other antiparkinsonian drugs; as treatment continues, it may be necessary to reduce the dose of other drugs or gradually discontinue them. Madopar fast-acting tablets /dispersible/ “125” is a special dosage form for patients with dysphagia or akinesia in the early morning hours and in the afternoon or with the phenomena of “depletion of the effect of a single dose” or “increase in the latent period before the onset of the clinical effect of the drug.” If during the day the patient experiences pronounced motor fluctuations (the phenomenon of “exhaustion of the effect of a single dose”, the phenomenon of “on-off”), it is recommended either more frequent administration of correspondingly smaller single doses, or, which is preferable, the use of Madopar GSS “125”. It is better to start the transition to Madopar GSS “125” with the morning dose, maintaining the daily dose and dosage regimen of Madopar “125” or Madopar “250”. After 2-3 days, the dose is gradually increased by approximately 50%. The patient should be warned that his condition may temporarily worsen. Due to its pharmacokinetic properties, Madopar GSS “125” begins to act somewhat later. The clinical effect can be achieved faster by prescribing Madopar GSS “125” together with Madopar “125” capsules or dispersible tablets. This may be especially useful in the case of the first morning dose, which should be slightly higher than subsequent doses. The individual dose of Madopar GSS “125” must be selected slowly and carefully, the interval between dose changes should be at least 2-3 days. In patients with nocturnal symptoms, a positive effect was achieved by gradually increasing the evening dose of Madopar GSS “125” to 250 mg (2 capsules) before going to bed. To eliminate the pronounced effect of Madopar GSS “125” (dyskinesia), increasing the intervals between doses is more effective than reducing the single dose. If Madopar GSS “125” is not effective enough, it is recommended to return to the previous treatment with Madopar “125”, Madopar “250” and Madopar fast-acting tablets / dispersible / “125”. No dose adjustment is required in patients with mild or moderate renal impairment. Madopar is well tolerated by patients on hemodialysis. With long-term treatment, fluctuations may occur - episodes of “freezing”, weakening of the effect towards the end of the dose period, the “on-off” phenomenon. To eliminate these symptoms or reduce their severity, dose adjustments should be made, possibly by prescribing smaller doses, but more often. Subsequently, you can try to increase the dose again to enhance the therapeutic effect. Restless legs syndrome To avoid worsening symptoms of restless legs syndrome (early appearance during the day, increasing severity and involvement of other parts of the body), the daily dose should not exceed the recommended maximum dose of 500 mg (400 mg levodopa + 100 mg benserazide) Madopara. If clinical symptoms increase, the dose of levodopa should be reduced or levodopa should be gradually discontinued and other therapy should be prescribed.

Interaction

Pharmacokinetic interaction

Trihexyphenidyl (an anticholinergic drug) reduces the rate, but not the extent, of absorption of levodopa. The administration of trihexyphenidyl together with Madopar® GSS “125” does not affect other parameters of the pharmacokinetics of levodopa.

Antacids reduce the degree of absorption of levodopa by 32% when prescribed with Madopar® GSS "125".

Ferrous sulfate reduces the plasma levodopa Cmax and AUC by 30–50%, which is a clinically significant change in some patients.

Metoclopramide increases the rate of absorption of levodopa.

Levodopa does not interact pharmacokinetically with bromocriptine, amantadine, selegiline and domperidone.

Pharmacodynamic interaction

Neuroleptics, opiates and antihypertensive drugs containing reserpine suppress the effect of Madopar®.

MAO inhibitors. If Madopar® is prescribed to patients receiving irreversible non-selective MAO inhibitors, then at least 2 weeks must elapse from stopping the MAO inhibitor before starting Madopar® (see “Contraindications”). However, selective MAO-B inhibitors (such as selegiline or rasagiline) and selective MAO-A inhibitors (such as moclobemide) can be prescribed to patients taking Madopar®. It is recommended to adjust the dose of levodopa depending on the patient's individual needs in terms of effectiveness and tolerability. The combination of MAO-A and MAO-B inhibitors is equivalent to taking a non-selective MAO inhibitor, therefore such a combination should not be prescribed simultaneously with Madopar®.

Sympathomimetics (adrenaline, norepinephrine, isoproterenol, amphetamine). Madopar® should not be prescribed simultaneously with sympathomimetics, since levodopa may potentiate their effect. If concomitant use is still necessary, careful monitoring of the cardiovascular system and, if necessary, reducing the dose of sympathomimetics are very important.

Antiparkinsonian drugs. The combined use of the drug with other antiparkinsonian drugs (anticholinergics, amantadine, dopamine agonists) is possible, but this may enhance not only the desired, but also the undesirable effects. It may be necessary to reduce the dose of Madopar® or another drug. If a catechol-o-methyltransferase inhibitor (COMT) is added to treatment, a reduction in the dose of Madopar® may be required. When starting Madopar® therapy, anticholinergic drugs should not be discontinued abruptly, since levodopa does not begin to act immediately.

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

In patients receiving Madopar®, taking the drug simultaneously with a protein-rich meal may interfere with the absorption of levodopa from the gastrointestinal tract.

General anesthesia with halothane. Taking Madopar® should be discontinued 12–48 hours before surgery, since a patient receiving Madopar® may experience blood pressure fluctuations and arrhythmia during halothane anesthesia.

Madopar “125” dispersible tablets 100 mg+25 mg 100 pcs.

Capsules (Madopar “125” or Madopar GSS “125”) should be swallowed whole without chewing. Madopar GSS “125” capsules cannot be opened before use, otherwise the effect of the modified release of the active substance is lost. Parkinson's disease. Orally, at least 30 minutes before or 1 hour after meals. Standard dosage regimen. Treatment should be started gradually, with individual doses adjusted until the optimal effect is achieved. Initial therapy At the early stage of Parkinson's disease, it is recommended to begin treatment with Madopar by taking 62.5 mg (50 mg levodopa + 12.5 mg benserazide) 3-4 times a day. If the initial dosing schedule is tolerated, the dose should be increased slowly based on patient response. The optimal effect is usually achieved with a daily dose of 300-800 mg levodopa + 75-200 mg benserazide, taken in three or more divided doses. It may take 4 to 6 weeks to achieve optimal results. If it is necessary to further increase the daily dose, this should be done at intervals of 1 month. Maintenance therapy. The average maintenance dose is 125 mg (100 mg levodopa + 25 mg benserazide) 3-6 times a day. The number of doses (at least three) and their distribution throughout the day should ensure optimal effect. To optimize the effect, you can replace Madopar “125” capsules and Madopar “250” tablets with Madopar fast-acting tablets /dispersible/ “125” or Madopar GSS “125” capsules. Restless legs syndrome. The maximum permissible dose per day is 500 mg of Madopar (400 mg of levodopa + 100 mg of benserazide). 1 hour before bedtime with a small amount of food. Before using Madopar, you should refrain from eating foods rich in protein. Idiopathic restless legs syndrome with sleep disturbances It is recommended to prescribe Madopar “125” capsules or Madopar “250” tablets. Initial dose: 62.5 mg (50 mg levodopa + 12.5 mg benserazide) - 125 mg (100 mg levodopa + 25 mg benserazide) Madopara. If the effect is insufficient, the dose should be increased to 250 mg (200 mg levodopa + 50 mg benserazide) of Madopar. Idiopathic restless legs syndrome with sleep and sleep disorders Initial dose: 1 capsule of Madopar GSS “125” and 1 capsule of Madopar “125” 1 hour before bedtime. If the effect is insufficient, it is recommended to increase the dose of Madopar GSS “125” to 250 mg (2 capsules). Idiopathic restless legs syndrome with problems falling asleep and sleeping, as well as disturbances during the day. Additionally: 1 dispersible tablet or 1 capsule Madopar “125”, the maximum permissible daily dose is 500 mg (400 mg levodopa + 100 mg benserazide) Madopar. “Restless legs” syndrome in patients with chronic renal failure receiving dialysis 125 mg Madopar (1 dispersible tablet or 1 capsule Madopar “125”) 30 minutes before the start of dialysis. Dosing in special cases. Parkinson's disease. Madopar can be combined with other antiparkinsonian drugs; as treatment continues, it may be necessary to reduce the dose of other drugs or gradually discontinue them. Madopar fast-acting tablets /dispersible/ “125” is a special dosage form for patients with dysphagia or akinesia in the early morning hours and in the afternoon or with the phenomena of “depletion of the effect of a single dose” or “increase in the latent period before the onset of the clinical effect of the drug.” If during the day the patient experiences pronounced motor fluctuations (the phenomenon of “exhaustion of the effect of a single dose”, the phenomenon of “on-off”), it is recommended either more frequent administration of correspondingly smaller single doses, or, which is preferable, the use of Madopar GSS “125”. It is better to start the transition to Madopar GSS “125” with the morning dose, maintaining the daily dose and dosage regimen of Madopar “125” or Madopar “250”. After 2-3 days, the dose is gradually increased by approximately 50%. The patient should be warned that his condition may temporarily worsen. Due to its pharmacokinetic properties, Madopar GSS “125” begins to act somewhat later. The clinical effect can be achieved faster by prescribing Madopar GSS “125” together with Madopar “125” capsules or dispersible tablets. This may be especially useful in the case of the first morning dose, which should be slightly higher than subsequent doses. The individual dose of Madopar GSS “125” must be selected slowly and carefully, the interval between dose changes should be at least 2-3 days. In patients with nocturnal symptoms, a positive effect was achieved by gradually increasing the evening dose of Madopar GSS “125” to 250 mg (2 capsules) before going to bed. To eliminate the pronounced effect of Madopar GSS “125” (dyskinesia), increasing the intervals between doses is more effective than reducing the single dose. If Madopar GSS “125” is not effective enough, it is recommended to return to the previous treatment with Madopar “125”, Madopar “250” and Madopar fast-acting tablets / dispersible / “125”. No dose adjustment is required in patients with mild or moderate renal impairment. Madopar is well tolerated by patients on hemodialysis. With long-term treatment, fluctuations may occur - episodes of “freezing”, weakening of the effect towards the end of the dose period, the “on-off” phenomenon. To eliminate these symptoms or reduce their severity, dose adjustments should be made, possibly by prescribing smaller doses, but more often. Subsequently, you can try to increase the dose again to enhance the therapeutic effect. Restless legs syndrome. To avoid an increase in the symptoms of restless legs syndrome (early appearance during the day, increasing severity and involvement of other parts of the body), the daily dose should not exceed the recommended maximum dose of 500 mg (400 mg levodopa + 100 mg benserazide) of Madopar. If clinical symptoms increase, the dose of levodopa should be reduced or levodopa should be gradually discontinued and other therapy should be prescribed.

Directions for use and doses

Orally, at least 30 minutes before or 1 hour after meals.

Capsules (Madopar® “125” or Madopar® GSS “125”) should be swallowed whole without chewing. Madopar® GSS “125” capsules cannot be opened before use, otherwise the effect of the modified release of the active substance is lost.

Tablets (Madopar® 250) can be crushed to make them easier to swallow.

Dispersible tablets (Madopar® fast-acting tablets (dispersible) “125”) should be dissolved in 1/4 cup of water (25–50 ml); The tablet dissolves completely after a few minutes to form a milky-white suspension, which should be taken no later than 30 minutes after the tablet has dissolved. Since a precipitate can quickly form, it is recommended to stir the solution before use.

Parkinson's disease

Standard dosage regimen

Treatment should be started gradually, with individual doses adjusted until the optimal effect is achieved.

Initial therapy

At the early stage of Parkinson's disease, it is recommended to start treatment with Madopar® with 62.5 mg (50 mg levodopa + 12.5 mg benserazide) 3-4 times a day. If the initial dosing schedule is tolerated, the dose should be increased slowly based on patient response.

The optimal effect is usually achieved with a daily dose of 300–800 mg levodopa + 75–200 mg benserazide, taken in 3 or more divided doses. It may take 4 to 6 weeks to achieve optimal effect. If it is necessary to further increase the daily dose, this should be done at intervals of 1 month.

Maintenance treatment

The average maintenance dose is 125 mg (100 mg levodopa + 25 mg benserazide) 3-6 times a day. The number of doses (at least 3) and their distribution throughout the day should ensure optimal effect.

To optimize the effect, you can replace Madopar® “125” capsules and Madopar® “250” tablets with Madopar® fast-acting tablets (dispersible) or Madopar® GSS “125” capsules.

Restless legs syndrome

The maximum permissible dose is 500 mg/day Madopar® (400 mg levodopa + 100 mg benserazide). 1 hour before bedtime, with a small amount of food.

Idiopathic restless legs syndrome with sleep disturbances

It is recommended to prescribe Madopar® “125” capsules or Madopar® “250” tablets.

Initial dose: 62.5 mg (50 mg levodopa + 12.5 mg benserazide)–125 mg (100 mg levodopa + 25 mg benserazide) Madopar®. If the effect is insufficient, the dose should be increased to 250 mg (200 mg levodopa + 50 mg benserazide) Madopar®.

Idiopathic restless legs syndrome with sleep and sleep disorders

Initial dose: 1 capsule. Madopar® GSS “125” and 1 caps. Madopar® “125” 1 hour before bedtime. If the effect is insufficient, it is recommended to increase the dose of Madopar® GSS “125” to 250 mg (2 capsules).

Idiopathic restless legs syndrome with difficulty falling asleep and staying asleep, as well as disturbances during the day

Additionally: 1 table. dispersible or 1 cap. Madopar® "125", the maximum permissible daily dose is 500 mg (400 mg levodopa + 100 mg benserazide).

Restless legs syndrome in patients with chronic renal failure receiving dialysis

125 mg Madopar® (1 dispersible tablet or 1 capsule Madopar® “125”) 30 minutes before the start of dialysis.

Dosing in special cases

Parkinson's disease

Madopar® can be combined with other antiparkinsonian drugs; as treatment continues, it may be necessary to reduce the dose of other drugs or gradually discontinue them.

Madopar® fast-acting tablets (dispersible) “125” is a special dosage form for patients with dysphagia or akinesia in the early morning and afternoon, or with the phenomena of “depletion of the effect of a single dose” or “increase in the latent period before the onset of the clinical effect of the drug” .

If during the day the patient experiences pronounced motor fluctuations (the phenomenon of “exhaustion of the effect of a single dose”, the phenomenon of “on-off”), it is recommended either more frequent administration of correspondingly smaller single doses, or, which is preferable, the use of Madopar® GSS “125”.

It is best to start the transition to Madopar® GSS "125" with the morning dose, maintaining the daily dose and dosage regimen of Madopar® "125" or Madopar® "250".

After 2–3 days, the dose is gradually increased by approximately 50%. The patient should be warned that his condition may temporarily worsen. Due to its pharmacological properties, Madopar® GSS “125” begins to act somewhat later. The clinical effect can be achieved faster by prescribing Madopar® GSS “125” together with Madopar® “125” capsules or dispersible tablets. This may be especially useful in the case of the first morning dose, which should be slightly higher than subsequent doses. The individual dose of Madopar® GSS “125” should be adjusted slowly and carefully, and the interval between dose changes should be at least 2–3 days.

In patients with nocturnal symptoms, a positive effect was achieved by gradually increasing the evening dose of Madopar® GSS “125” to 250 mg (2 capsules) before going to bed.

To eliminate the pronounced effect of Madopar® GSS “125” (dyskinesia), increasing the intervals between doses is more effective than reducing the single dose.

If Madopar® GSS "125" is not effective enough even at a daily dose corresponding to 1500 mg of levodopa, it is recommended to return to the previous treatment with Madopar® "125", Madopar® "250" and Madopar® fast-acting tablets (dispersible) "125".

No dose adjustment is required in patients with mild or moderate renal impairment.

Madopar® is well tolerated by patients receiving hemodialysis sessions.

With long-term therapy, episodes of “freezing”, “exhaustion phenomenon”, and “on-off” phenomena may occur. During episodes of “freezing” and the “exhaustion phenomenon,” they resort to splitting the dose of the drug (reducing the single dose or shortening the interval between doses of the drug), and when the “on-off” phenomenon occurs, increasing the single dose while reducing the number of doses. Subsequently, you can try to increase the dose again to enhance the effect of treatment.

Restless legs syndrome

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

If clinical symptoms increase, the dose of levodopa should be reduced or levodopa should be gradually discontinued and other therapy should be prescribed.

Madopar GSS 125 100mg+25mg caps modif vysv No. 100

Capsules (Madopar® “125” or Madopar® GSS “125”) should be swallowed whole without chewing. Madopar® GSS “125” capsules cannot be opened before use, otherwise the effect of the modified release of the active substance is lost.

Tablets (Madopar® 250) can be crushed to make them easier to swallow.

Dispersible tablets (Madopar® fast-acting tablets /dispersible/ “125”) should be dissolved in a quarter glass of water (25–50 ml); The tablet dissolves completely after a few minutes to form a milky-white suspension, which should be taken no later than half an hour after the tablet has dissolved. Since a precipitate can quickly form, it is recommended to stir the solution before use.

Parkinson's disease

Orally, at least 30 minutes before or 1 hour after meals.

Standard dosage regimen

Treatment should be started gradually, with individual doses adjusted until the optimal effect is achieved.

Initial therapy

At the early stage of Parkinson's disease, it is recommended to start treatment with Madopar® with 62.5 mg (50 mg levodopa + 12.5 mg benserazide) 3-4 times a day. If the initial dosing schedule is tolerated, the dose should be increased slowly based on patient response. The optimal effect is usually achieved with a daily dose of 300–800 mg levodopa + 75–200 mg benserazide, taken in three or more divided doses. It may take 4 to 6 weeks to achieve optimal results. If it is necessary to further increase the daily dose, this should be done at intervals of 1 month.

Maintenance therapy

The average maintenance dose is 125 mg (100 mg levodopa + 25 mg benserazide) 3-6 times a day. The number of doses (at least three) and their distribution throughout the day should ensure optimal effect.

To optimize the effect, you can replace Madopar® “125” capsules and Madopar® “250” tablets with Madopar® fast-acting tablets /dispersible/ “125” or Madopar® GSS “125” capsules.

Restless legs syndrome

The maximum permissible dose per day is 500 mg Madopar® (400 mg levodopa + 100 mg benserazide).

1 hour before bedtime with a small amount of food. Before using Madopar®, you should refrain from eating foods rich in protein.

Idiopathic restless legs syndrome with sleep disturbances

It is recommended to prescribe Madopar® “125” capsules or Madopar® “250” tablets.

Initial dose: 62.5 mg (50 mg levodopa + 12.5 mg benserazide) - 125 mg (100 mg levodopa + 25 mg benserazide) Madopar®. If the effect is insufficient, the dose should be increased to 250 mg (200 mg levodopa + 50 mg benserazide) Madopar®.

Idiopathic restless legs syndrome with sleep and sleep disorders

Initial dose: 1 capsule of Madopar® GSS “125” and 1 capsule of Madopar® “125” 1 hour before bedtime. If the effect is insufficient, it is recommended to increase the dose of Madopar® GSS “125” to 250 mg (2 capsules).

Idiopathic restless legs syndrome with difficulty falling asleep and staying asleep, as well as disturbances during the day

Additionally: 1 dispersible tablet or 1 capsule Madopar® “125”, the maximum permissible daily dose is 500 mg (400 mg levodopa + 100 mg benserazide) Madopar®.

Restless legs syndrome in patients with chronic renal failure receiving dialysis

125 mg Madopar® (1 dispersible tablet or 1 capsule Madopar® “125”) 30 minutes before the start of dialysis.

Dosing in special cases

Parkinson's disease

Madopar® can be combined with other antiparkinsonian drugs; as treatment continues, it may be necessary to reduce the dose of other drugs or gradually discontinue them.

Madopar® fast-acting tablets /dispersible/ “125” is a special dosage form for patients with dysphagia or akinesia in the early morning hours and in the afternoon or with the phenomena of “depletion of the effect of a single dose” or “increase in the latent period before the onset of the clinical effect of the drug.”

If during the day the patient experiences pronounced motor fluctuations (the phenomenon of “exhaustion of the effect of a single dose”, the phenomenon of “on-off”), it is recommended either more frequent administration of correspondingly smaller single doses, or, which is preferable, the use of Madopar® GSS “125”.

It is better to start the transition to Madopar® GSS "125" with the morning dose, maintaining the daily dose and dosage regimen of Madopar® "125" or Madopar® "250".

After 2–3 days, the dose is gradually increased by approximately 50%. The patient should be warned that his condition may temporarily worsen. Due to its pharmacokinetic properties, Madopar® GSS “125” begins to act somewhat later. The clinical effect can be achieved faster by prescribing Madopar® GSS “125” together with Madopar® “125” capsules or dispersible tablets. This may be especially useful in the case of the first morning dose, which should be slightly higher than subsequent doses. The individual dose of Madopar® GSS "125" must be selected slowly and carefully, the interval between dose changes should be at least 2-3 days.

In patients with nocturnal symptoms, a positive effect was achieved by gradually increasing the evening dose of Madopar® GSS “125” to 250 mg (2 capsules) before going to bed.

To eliminate the pronounced effect of Madopar® GSS “125” (dyskinesia), increasing the intervals between doses is more effective than reducing the single dose.

If Madopar® GSS “125” is not effective enough, it is recommended to return to the previous treatment with Madopar® “125”, Madopar® “250” and Madopar® fast-acting tablets /dispersible/ “125”.

No dose adjustment is required in patients with mild or moderate renal impairment.

Madopar® is well tolerated by patients on hemodialysis.

With long-term treatment, fluctuations may occur - episodes of “freezing”, weakening of the effect towards the end of the dose period, the “on-off” phenomenon. To eliminate these symptoms or reduce their severity, dose adjustments should be made, possibly by prescribing smaller doses, but more often. Subsequently, you can try to increase the dose again to enhance the therapeutic effect.

Restless legs syndrome

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

If clinical symptoms increase, the dose of levodopa should be reduced or levodopa should be gradually discontinued and other therapy should be prescribed.

Overdose

Symptoms: from the cardiovascular system - arrhythmias; mental sphere - confusion, insomnia; from the gastrointestinal tract - nausea and vomiting; pathological involuntary movements (mentioned in the “Side effects” section, but in a more pronounced form).

When taking modified-release capsules (Madopar® GSS "125"), the onset of overdose symptoms may occur later due to slow absorption of the active substances in the stomach.

Treatment: it is necessary to monitor vital functions; symptomatic therapy - the prescription of respiratory analeptics, antiarrhythmic drugs, and, in appropriate cases, neuroleptics.

When using a dosage form with a modified release of active substances (Madopar® GSS “125”), further absorption of the drug should be prevented.

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** The Drug Directory is intended for informational purposes only. For more complete information, please refer to the manufacturer's instructions. Do not self-medicate; Before starting to use the drug Madopar fast-acting tablets (dispersible) “125” you should consult a doctor. EUROLAB is not responsible for the consequences caused by the use of information posted on the portal. Any information on the site does not replace medical advice and cannot serve as a guarantee of the positive effect of the drug.

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special instructions

Persons with hypersensitivity to the drug may develop corresponding reactions.

In patients with open-angle glaucoma, it is recommended that intraocular pressure be measured regularly because levodopa may theoretically increase intraocular pressure.

Side effects from the gastrointestinal tract, which are possible at the initial stage of treatment, can be largely eliminated if Madopar® is taken with a small amount of food or liquid, and also if the dose is increased slowly.

During treatment, it is necessary to monitor liver and kidney function and blood count.

Patients with diabetes need to frequently monitor blood glucose levels and adjust the dose of hypoglycemic drugs.

If surgery with general anesthesia is necessary, Madopar® therapy should be continued until surgery, with the exception of general anesthesia with halothane. Since blood pressure fluctuations and arrhythmia may occur in a patient receiving Madopar® during halothane anesthesia, Madopar® should be discontinued 12–48 hours before surgery. After surgery, treatment is resumed, gradually increasing the dose to the previous level.

Madopar® should not be discontinued abruptly. Abrupt discontinuation of the drug may lead to “neuroleptic malignant syndrome” (fever, muscle stiffness, as well as possible mental changes and increased serum creatine phosphokinase), which can become life-threatening. If such symptoms occur, the patient should be under medical supervision (if necessary, hospitalized) and receive appropriate symptomatic therapy. This may include re-prescribing Madopar® after appropriate assessment of the patient's condition.

Depression can be either a clinical manifestation of the underlying disease (parkinsonism, restless legs syndrome) or occur during Madopar® therapy. The patient should be carefully monitored for the possible occurrence of psychiatric adverse reactions.

Possibility of drug dependence and abuse

Some patients with Parkinson's disease have experienced 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 significantly exceeding therapeutic doses of the drug.

Impact on driving vehicles and working with machines and mechanisms

If drowsiness occurs, incl. sudden episodes of drowsiness, you should avoid driving a car or working with machinery. If these symptoms occur, dose reduction or discontinuation of therapy should be considered.

Madopar 125 mg n100 caps.