Madopar "250" - instructions for use, dose, side effects, contraindications

Excipients: citric acid anhydrous - 20.0 mg, corn pregelatinised corn starch - 41.5 mg, microcrystalline cellulose - 303.0 mg, magnesium stearate - 7.0 mg.

One capsule contains:

active substances: levodopa - 100 mg, benserazid - 25 mg (in the form of benserazid hydrochloride 28.5 mg);

Excipients: cellulose microcrystalline - 13.5 mg, talc - 6.5 mg, povidone - 1.0 mg, magnesium stearate - 0.5 mg; shell: cap capsule - dye indigocarmine (E132) 0.01 mg, titanium dioxide (E171) 0.5 mg, gelatin 21.0 mg; Capsule casing - iron dye red oxide (E172) 0.03 mg, titanium dioxide (E171) 1.12 mg, gelatin 31.2 mg.

One tablet contains:

active substances: levodopa - 200 mg, benserazid - 50 mg (in the form of benserazide hydrochloride 57 mg);

Excipients: mannitol - 103.2 mg, calcium hydrophosphate - 100.0 mg, microcrystalline cellulose - 38.6 mg, corn pregelatinized corn starch - 20.0 mg, crospovidone - 20.0 mg, ethyl cellulose 3.0 mg, iron dye red oxide -1.5 mg, silicon dioxide colloid (anhydrous) -1.0 mg, sodium docusate 0.2 mg, magnesium stearate 5.5 mg.

One capsule with modified release (GCC capsule - hydrodynamically balanced system) contains:

active substances: levodopa - 100 mg, benserazid - 25 mg (in the form of benserazid hydrochloride 28.5 mg);

Excipients: hypromellose -115.0 mg, vegetable hydrogenated oil 30.0 mg, calcium hydrophosphate 27.5 mg, mannitol 18.0 mg, povidone 6.0 mg, talc 10.0 mg, magnesium stearate 5.0 mg; shell: cap capsule - dye indigocarmine (E132) 0.09 mg, iron dye oxide yellow (E172) 0.53 mg, titanium dioxide (E171) 0.31 mg, gelatin 25.3 mg; the capsule body - indigo carmine dye (E132) 0.02 mg, titanium dioxide (E171) 0.92 mg, gelatin 38.3 mg.

Description:

Tablets are dispersible: cylindrical, flat on both sides tablets with beveled edges, white or almost white, odorless or slightly odorless, slightly marble, engraved with "ROCHE 125" on one side of the tablet and a fault line on the other side.The diameter of the tablet is about 11 mm; thickness about 4.2 mm.

Capsules: hard gelatin capsules number 2; body pinkish-flesh colored, opaque; lid of light blue color, opaque; on the capsule there is an inscription "ROCHE" of black color. The contents of the capsules are a fine granular powder, sometimes crumpled, of a light beige color.

Tablets: cylindrical flat tablets with beveled edges, pale red with small patches; on one side of the tablet crosswise risk, engraving "ROCHE" and hexagon; on the other side of the pill - a cruciform risk. The diameter of the tablet is 12.6-13.4 mm; thickness 3-4 mm.

Capsules with modified release: hard gelatin capsules # 1; the body is light-blue in color, opaque; lid of dark green color, opaque; on the capsule there is an inscription "ROCHE" of rusty-red color.

The contents of the capsules are a fine granular powder, sometimes crumpled, white or slightly yellowish in color.

Pharmacotherapeutic group:An antiparkinsonian agent (dopamine precursor + decarboxylase peripheral inhibitor).

ATX: & nbsp

N.04.B.A Dopa and dopa derivatives

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

Pharmacodynamics:

A combined agent for the treatment of Parkinson's disease and the syndrome of "restless legs"

Parkinson's disease

Dopamine, which is a neurotransmitter in the brain, in patients with Parkinsonism is formed in the basal ganglia in insufficient quantities. Levodopa or L-DOPA (3,4-dihydrophenylalanine) is a metabolic precursor of dopamine. Unlike dopamine levodopa well penetrates the blood-brain barrier. After levodopa penetrates the central nervous system, it is converted to dopamine by decarboxylase of aromatic L-amino acids. After oral administration levodopa It is rapidly decarboxylated into dopamine in both cerebral and extracerebral tissues. As a result, most of the levodopa does not reach the basal ganglia, and peripheral dopamine often causes side effects. Therefore, it is necessary to block extracerebral decarboxylation of levodopa, which is achieved by simultaneous administration of levodopa and benserazide, an inhibitor of peripheral decarboxylase of aromatic L-amino acids.

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

Syndrome of "restless legs"

The exact mechanism of action is not known, but the dopaminergic system plays an important role in the pathogenesis of the restless legs syndrome.

Pharmacokinetics:

Suction

Capsules Madopar "125" and tablets Madopar "250"

Absorption of levodopa and benserazide occurs mainly in the upper parts of the small intestine (66-74%) and does not depend on the site of absorption in this part of the intestine. The time to reach the maximum concentration of levodopa in plasma is 1 hour after taking capsules or tablets. Madopar Capsules 125 and Madopar 250 tablets are bioequivalent when taken in the same molar dose. Absolute bioavailability of levodopa in Madopar 125 capsules and Madopar 250 tablets is 98% (from 74% to 112%). Maximum concentrations of levodopa in plasma and the degree of absorption of levodopa (AUC) increase in proportion to the dose (in the dose range of levodopa from 50 to 200 mg). Eating food reduces the rate and degree of absorption of levodopa. When prescribing capsules or tablets after meals, the maximum concentration of levodopa in the plasma decreases by 30% and is reached later. The degree of absorption of levodopa decreases by 15%.

Madopar high-speed tablets / dispersible / "125"

Pharmacokinetic profiles of levodopa after administration of dispersible tablets are similar to those after taking Madopar 125 capsules or Madopar 250 tablets, but the time to reach maximum concentrations tends to decrease. The parameters of absorption of dispersible tablets in patients are less variable.

Capsules with modified release Madopar GSS "125"

Madopar GSA "125" has other pharmaco-kinetic properties than the above-mentioned release forms. Active substances are released slowly in the stomach. The maximum concentration in plasma is 20-30% of that after taking Madopar 125 capsules and Madopar 250 tablets, and is reached 3 hours after ingestion. The dynamics of plasma concentration is characterized by a longer half-life (a period of time in which the plasma concentration is greater than or equal to half the maximum) than Madopar 125 capsules and Madopar 250 tablets, indicating continuous, modifiable release. The bioavailability of the Madopar GSS 125 preparation is 50-70% of the bioavailability of the Madopar 125 capsules and the Madopar 250 tablets and is not dependent on food intake.The intake of food does not affect the maximum concentration of levodopa, which under this condition is achieved after 5 hours at the reception of Madopar GSS "125".

Distribution

Levodopa passes through the blood-brain barrier through a saturated transport system and does not bind to plasma proteins. The volume of distribution is 57 liters. The area under the concentration-time curve (AUC) for levodopa in cerebrospinal fluid is 12% of that in plasma. Benserazid in therapeutic doses does not penetrate the blood-brain barrier. 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) pathways.

Decarboxylase of aromatic L-amino acids converts levodopa into dopamine. The main end products of this pathway are homovaniline and dihydroxyphenyl-l-acetic acids.

Catechol-o-methyl transferase methylates levodopa to form 3-o-methyldopa. The half-life of this basic metabolite from plasma is 15-17 hours, and in patients taking therapeutic doses of Madopar, its accumulation takes place.Reduction of peripheral decarboxylation of levodopa, when co-administered with benserazide, leads to higher plasma concentrations of levodopa and 3-o-methyldopa and lower plasma concentrations of catecholamines (dopamine, norad-reninal) and phenol carboxylic acids (homovanilic acid, dihydrophenylacetic acid).

In the mucous membrane of the intestine and liver, benserazide is hydroxylated to form trihydroxy-benzylhydrazine. This metabolite is a potent inhibitor of decarboxylase of aromatic L-amino acids.

Excretion

With peripheral inhibition of decarboxylase of aromatic L-amino acids, the half-life of levodopa is 1.5 hours. The clearance of levodopa from plasma is approximately 430 ml / min.

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

Pharmacokinetics in specific patient groups

Patients with renal and hepatic insufficiency

Data on the pharmacokinetics of levodopa in patients with renal and hepatic insufficiency are absent.

Patients of senile age (65-78 years)

In patients of senile age (65-78 years) with Parkinson's disease the half-life and AUC of levodopa increase by 25%, which is not a clinically significant change and does not affect the dosage regimen.

Indications:

Parkinson's disease:

Madopar is indicated for the treatment of Parkinson's disease.

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

Madopar SCA 125 is shown for all types of fluctuations in the action of levodopa (namely: "dyskinesia peak dose" and "end-of-dose phenomenon," for example, immobility at night).

Syndrome of restless legs:

Madopar is indicated for the treatment of restless legs syndrome, including:

- idiopathic syndrome of "restless legs"

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

Contraindications:

Hypersensitivity to levodopa, benserazide or any other component of the drug.Decompensated dysfunction of endocrine organs, liver or kidneys (except for patients with the syndrome of restless legs receiving dialysis), cardiovascular disease in the stage of decompensation, mental illness with a psychotic component, closed-angle glaucoma.

Madopar should not be used in combination with nonselective monoamine oxidase (MAO) inhibitors or when combined with MAO-A and MAO-B inhibitors.

Age younger than 25 years. Pregnancy and lactation. Madopar is contraindicated in women of childbearing age who do not use reliable methods of contraception (see "Pregnancy and the period of breastfeeding").

Pregnancy and lactation:

Madopar is absolutely contraindicated in pregnancy and 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 on the background of treatment, the drug should be discontinued in accordance with the recommendations of the treating doctor.

If you need to take Medopar during breastfeeding, you should stop breastfeeding, due to the lack of reliable data on the penetration of benserazide into breast milk.It is impossible to exclude the danger of incorrect development of the skeleton in the newborn.

Dosing and Administration:

Capsules (Madopar "125" or Madopar GSA "125") should be swallowed whole, without chewing. Capsules Madopar GSA "125" can not be opened before use, otherwise the effect of modified release of the active substance is lost.

Tablets (Madopar "250") can be crushed to facilitate swallowing. Dispersible tablets (Madopar high-speed tablets / dispersible / "125") should be dissolved in a quarter cup of water (25-50 ml); the tablet is completely dissolved after a few minutes to form a milky white suspension, which should be taken no later than half an hour after dissolving the tablet. Since a precipitate can form rapidly, it is recommended to mix the solution before use.

Parkinson's disease

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

Standard dosing regimen

Treatment should be started gradually, individually picking up the dose to the optimum effect.

Initial therapy

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

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

Supportive therapy

The average maintenance dose is -125 mg (100 mg of levodopa + 25 mg of benserazide) 3-6 times a day. The number of receptions (at least three) and their distribution during the day should provide the optimal effect. To optimize the effect, you can replace Madopar 125 capsules and Madopar 250 tablets with Madopar high-speed tablets / dispersible / 125 or Madopar GSO 125 capsules. Syndrome of "restless legs"

The maximum allowable dose per day is 500 mg Madopara (400 mg levodopa + 100 mg benserazide).

1 hour before bedtime with a small amount of food. Before applying the drug Madopar should refrain from eating a meal rich in protein.

Idiopathic syndrome of restless legs with disturbed sleep

It is recommended that Madopar 125 capsules or Madopar 250 tablets be prescribed.Initial dose: 62.5 mg (50 mg of levodopa + 12.5 mg of benserazide) -125 mg (100 mg of levodopa + 25 mg of benserazide) Madopar. If the effect is insufficient, you should increase the dose to 250 mg (200 mg of levodopa + 50 mg of benserazide) Madopar.

Idiopathic syndrome of restless legs with disturbed sleep and sleep

The initial dose: 1 capsule Madopar GSS "125" and 1 capsule Madopar "125" for 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 syndrome of "restless legs" with disturbances of falling asleep and sleep, as well as with disturbances during the day

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

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

125 mg Madopara (1 tablet dispersible or 1 Madopar capsule "125") 30 minutes before the start of dialysis.

Dosing in special cases

Parkinson's disease

Madopar can be combined with other antiparkinsonian means, as the treatment continues, it may be necessary to reduce the dose of other drugs or their gradual cancellation.Madopar high-speed tablets / dispersible / "125" - a special dosage form for patients with dysphagia or akinesia in the early morning hours and in the afternoon or in the phenomena 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 exhibits pronounced 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 - which is preferable - the use of Madopar GSS "125". It is better to start the transition to Madopar SCA "125" from the morning dose, keeping the daily dose and the Madopar "125" or Madopara "250" reception scheme.

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. Clinical effect can be achieved more quickly by appointing Madopar GSS "125" together with Madopar "125 capsules" or tablets dispersible. This can be especially useful in the case of the first morning dose, which should be slightly higher than the subsequent ones.Individual dose of Madopar GSS "125" 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 "125" to 250 mg (2 capsules) before going to bed.

To eliminate the pronounced 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, it is recommended to return to the previous treatment with Madopar "125", Madopar "250" and Madopar high-speed tablets / dispersible / "125". In patients with mild or moderate renal insufficiency, dose adjustment is not required. Madopar is well tolerated by patients on hemodialysis. With long-term treatment, there may appear fluctuations - episodes of "congealing", weakening of the effect by the end of the period of the dose, the phenomenon of "on-off". To eliminate these symptoms or reduce their severity, dose adjustment should be performed, possibly by administering smaller doses, but more often.Subsequently, you can try to increase the dose again to enhance the therapeutic effect.

Syndrome of "restless legs"

To avoid the increase in 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 500 mg (400 mg levodopa + 100 mg benserazide) Madopara. With the increase in clinical symptoms should reduce the dose of levodopa or gradually cancel levodopa and prescribe another therapy.

Side effects:

On the part of the blood system: rare cases of hemolytic anemia, transient leukopenia, thrombocytopenia. In patients taking long-term levodopa, it is recommended to periodically monitor the blood formula, the function of the liver and kidneys.

From the gastrointestinal tract: nausea, vomiting, diarrhea, individual cases of loss or changes in taste, dryness of the oral mucosa.

From the skin and its appendages: rarely - itching, rash.

From the cardiovascular system: arrhythmias, orthostatic hypotension (weakening after a reduction in 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 who have had these symptoms in history), depression, headache, dizziness, in later stages of treatment, sometimes spontaneous movements (such as chorea or atheroses), episodes of "hardening", weakening of the effect by the end of the period of the dose action (the phenomenon of "exhaustion"), the phenomenon of "on-off", pronounced drowsiness, episodes of sudden drowsiness, increased manifestations of the syndrome of restless legs.

On the part of the body as a whole: febrile infection, rhinitis, bronchitis.

Laboratory indicators: sometimes transient increase in hepatic transaminase and alkaline phosphatase activity, increase of gamma-glutamyltranspeptidase, increase of blood urea nitrogen, change of urine color to red, darkening on standing.

On the part of the body as a whole: anorexia

Overdose:

Symptoms: mentioned in the section "Side effects", but in a more pronounced form: from the cardiovascular system (arrhythmia), the psychic sphere (confusion, insomnia), from the gastrointestinal tract (nausea and vomiting), pathological involuntary movements.

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

Therapy: it is necessary to monitor vital functions. Symptomatic therapy: respiratory analeptics, antiarrhythmics, if appropriate, antipsychotics.

When using the capsules with modified release of active substances (Madopar GSS "125"), further absorption of the drug should be prevented.

Interaction:

Trihexyphenidyl (anticholinergic drug) reduces the rate, but not the degree of absorption of levodopa. The administration of trihexyphenidyl together with Madopar SCA "125" does not affect the pharmacokinetics of levodopa.

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

Ferrous Sulphate reduces the maximum concentrations and AUC of levodopa in plasma by 30-50%, which is a clinically significant change in some but not all patients.

Metoclopramide increases the rate of absorption of levodopa. Levodopa does not enter into pharmacokinetic interactions with bromocriptine, amantadine, selegiline and domperidone.

Pharmacodynamic interactions

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

MAO inhibitors. If Madopar is prescribed to patients receiving irreversible non-selective MAO inhibitors, then at least two weeks should elapse from discontinuing the use of 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 administered to patients receiving Madopar. 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-A and MAO-B inhibitors is equivalent to the use of a non-selective MAO inhibitor, so a similar combination should not be administered concomitantly with Madopar.

Sympathomimetics (epinephrine, norepinephrine, isoproterenol, amphetamine). Madopar should not be prescribed simultaneously with sympathomimetics, since levodopa can potentiate their action. If simultaneous reception is still necessary, careful monitoring of the cardiovascular system and, if necessary, a reduction in the dose of sympathomimetics is very important.

Antiparkinsonian means. It is possible to combine the drug with other antiparkinsonian drugs (anticholinergic, amantadine, dopamine agonists), but this can enhance the desired and undesirable effects. You may need to reduce the dose of Madopar or another drug. If a catechol-o-methyltransferase inhibitor (COMT) is added to the treatment, a dose reduction of Madopar may be required. When Madopar therapy is started, anticholinergic drugs should not be abruptly abolished, since levodopa begins to act not immediately.

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 foods can disrupt the absorption of levodopa from the gastrointestinal tract.

General anesthesia with halothane. Reception Madopara should be canceled for 12 - 48 hours before an operative intervention as at the patient receiving Madopar, during halotane anesthesia there can be fluctuations of arterial pressure and arrhythmias.

Special instructions:In patients with hypersensitivity to the drug, the development of appropriate reactions is possible.

Patients with open-angle glaucoma are advised to regularly monitor intraocular pressure, since theoretically levodopa may increase intraocular pressure. Side effects from the gastrointestinal tract, possible at the initial stage of treatment, can be largely eliminated if you take Madopar with a small amount of food or liquid, as well as if you increase the dose slowly. Care should be taken with peptic ulcer or history of osteomalacia.

In patients with myocardial infarction, ischemic heart disease or history of arrhythmia, heart function should be regularly assessed (in particular, by electrocardiography (ECG)).

During the treatment it is necessary to monitor the function of the liver and kidneys, the blood formula. Patients with diabetes must often monitor blood glucose levels and correct the dose of hypoglycemic drugs.

Medopar should not be used in patients with malignant melanoma (including in the case of a suspected diagnosis, the presence of unidentified skin formations or a history of malignant melanoma).

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

It should avoid the use of halothane or cyclopropane anesthesia for surgical operations in patients who did not stop taking Madopar (for example, in urgent cases).

Madopar can not be abolished abruptly. Abrupt withdrawal of the drug may lead to a malignant neuroleptic syndrome (fever, muscle stiffness, and possible mental changes and increased activity of serum creatinophosphinase), which can take a life-threatening form. If such symptoms occur, the patient should be under the supervision of a doctor (if necessary, should be hospitalized) and receive appropriate symptomatic therapy.It can include the re-appointment of Madopar after an appropriate assessment of the patient's condition. Depression can be both a clinical manifestation of the underlying disease (Parkinson's disease, restless legs syndrome), and it can occur on the background of Madopar therapy. The patient should be carefully observed in terms of the possible emergence of mental side effects.

Against the background of taking Madopar, there may be drowsiness and, in rare cases, episodes of sudden falling asleep. Episodes of sudden falling asleep can arise in the absence of preliminary drowsiness or other signs. Patients may not realize that they have developed an episode of sudden falling asleep, so they should be warned about the possible risk (see "Impact on driving vehicles and working with machines and mechanisms").

The possibility of drug dependence and abuse

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.

Dopaminergic drugs

Patients taking dopamine receptor agonists for the treatment of Parkinson's disease noted cases of pathological attraction to gambling, increased libido and hypersexuality. Confirmation of the existence of a causal relationship between the administration of Madopar, which does not belong to dopamine receptor agonists, and these phenomena do not exist. However, when prescribing Madopar, one should remember about the possibility of occurrence of these phenomena, since Madopar is a dopa-minergic drug.

Effect on the ability to drive transp. cf. and fur:If there is a drowsiness or episodes of a sudden falling asleep in an anamnesis, you should stop driving the car or work with machines and mechanisms. When these symptoms appear, you should consider reducing the dose or canceling therapy.

Form release / dosage:Dispersible tablets 100 mg + 25 mg, capsules 100 mg + 25 mg, tablets 200 mg + 50 mg, modified-release capsules (capsules GSS) 100 mg + 25 mg.

Packaging:Tablets dispersible 100 mg + 25 mg For 30 or 100 tablets in a glass bottle of brown color (hydrolytic class III EF),Capped with a screw cap (with silica gel inside) with autopsy control; on the cover is the logo <Roche>. Free space in the vial is filled with cotton absorbent cotton. Each vial with the instruction for use is placed in a cardboard box. Capsules 100 mg + 25 mg, tablets 200 mg + 50 mg, modified-release capsules (capsules GSS) 100 mg + 25 mg 30 or 100 capsules, tablets or capsules of GSS in bottles of brown glass with a screw cap on the inside capacity with silica gel. The lid is connected to a perforated plastic strip (first opening control). The surface of the cover is labeled <Roche>. Free space in the vial is filled with cotton wool or other sealing material. Each vial with the instruction for use is placed in a cardboard box.

Storage conditions:Tablets are dispersible - at a temperature of no higher than 25 ° C. Tablets - at a temperature of no higher than 25 ° C in a dry place. Capsules, capsules GCC - at a temperature of no higher than 30 ° C in a dry place. Keep out of the reach of children.

Shelf life:

Tablets are dispersible, capsules, capsules GCC - 3 years. Tablets - 4 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014069 / 01

Date of registration:22.07.2008

The owner of the registration certificate:Hoffmann-La Roche Ltd.Hoffmann-La Roche Ltd. Switzerland

Manufacturer: & nbsp

F.Hoffmann-La Roche, Ltd. Switzerland

Roche, S.p.A. Italy

Representation: & nbspF.Hoffmann-La Roche Ltd. F.Hoffmann-La Roche Ltd. Switzerland

Information update date: & nbsp24.08.2015

Illustrated instructions

Instructions

Madopar® "250" (Madopar® "250")