Expiration date: 02/2026
The composition and form of issue:
Fast acting madopar tablets (dispersible) "125"
Dispersible tablets, 1 tablet contains:
levodopa 100 mg
the benserazide 25 mg
(benserazide hydrochloride — 28,5 mg)
excipients: citric acid anhydrous, corn starch pregelatinization MCC magnesium stearate
in dark glass bottles of 30 or 100 PCs. in cardboard pack 1 bottle.
Madopar "125"
Capsules. 1 capsule contains:
levodopa 100 mg
the benserazide 25 mg
(benserazide hydrochloride — 28,5 mg)
other ingredients: microcrystalline povidone talc magnesium stearate
shell: the lid of the capsule — dye Indigo Carmine titanium dioxide gelatin body of the capsule — dye iron oxide red titanium dioxide gelatin
in dark glass bottles of 30 or 100 PCs. in cardboard pack 1 bottle.
Madopar "250"
Tablets, 1 tablet contains:
levodopa 200 mg
the benserazide 50 mg
(benserazide hydrochloride 57 mg)
auxiliary substances: mannitol, calcium hydrogen phosphate microcrystalline starch corn pregelatinization crospovidon ethyl cellulose dye iron oxide red silicon dioxide colloidal (anhydrous) sodium docusate magnesium stearate
in dark glass bottles of 30 or 100 PCs. in cardboard pack 1 bottle.
Madopar GSS "125"
Capsules GSS (hydrodynamically balanced system). 1 capsule contains:
levodopa 100 mg
the benserazide 25 mg
(benserazide hydrochloride — 28,5 mg)
excipients: hypromellose hydrogenated vegetable oil calcium hydrogen phosphate mannitol povidone talc magnesium stearate
shell: the lid of the capsule — dyes Indigo Carmine and iron oxide yellow titanium dioxide gelatin casing of the capsule — dye Indigo Carmine titanium dioxide, gelatin
in dark glass bottles of 30 or 100 PCs. in cardboard pack 1 bottle.
Description pharmaceutical form:
Dispersible tablets: cylindrical, flat on both sides with a beveled edge, white or almost white, odourless or weak smell, slightly marbled, engraved "ROCHE 125" on one side of the tablet and breakline on the other side. Tablet diameter is about 11 mm, a thickness of about 4.2 mm.
Capsules: hard gelatin shell — pinkish-flesh-colored, opaque cap and light — blue opaque for the capsule is marked "ROCHE" in black. The contents of capsules — fine granular powder, sometimes somavamsis, light beige color, with a subtle scent.
Tablets: round, flat beveled edge, pale red, with small patches, with a faint smell on one side of the pill the risk of cross-shaped, engraved "ROCHE" and a hexagon on the other — cross risk. Tablet diameter is 12.6 and 13.4 mm thickness — 3-4 mm.
Capsules with modified release: hard gelatin shell — light blue opaque cap — dark green, opaque on the capsule is marked "ROCHE" ink rusty-red color. The contents of capsules — fine granular powder, sometimes somavamsis, white or slightly yellowish, with a subtle scent.
Pharmacokinetics:
Suction
Capsules Madopar "125" and tablets of Madopar "250"
Levodopa is mainly absorbed in the upper small intestine. The time to reach Cmax of levodopa — 1 h after administration of capsules or tablets.
Capsules and tablets are bioequivalent.
Cmax of levodopa in the plasma and the extent of levodopa absorption (AUC) increase proportionally with dose (dose range of levodopa from 50 to 200 mg).
Food intake reduces the rate and extent of absorption of levodopa. In the appointment of capsules or tablets after a meal Cmax of levodopa in the plasma is reduced by 30% and is reached later. The degree of absorption of levodopa is reduced by 15%. The absolute bioavailability of levodopa in capsules of Madopar "125" and tablets Madopar "250" is 98% (from 74 to 112%).
Fast acting madopar tablets (dispersible) "125"
The pharmacokinetic profiles of levodopa after administration of the dispersible tablets was similar to that after administration of Madopar capsules "125" or tablets Madopar "250", but the time to reach Cmax tends to decrease. Settings suction dispersible tablets in patients less variable.
Madopar GSS "125" capsules with modified release of the active substance
Madopar GSS "125" has different pharmacokinetic properties than the above release form. The active substances are released in the stomach slowly. Cmax in plasma 20-30% less than conventional dosage forms, and is achieved through 3 h after administration. Dynamics concentration in plasma is characterized by a longer "half-life" (the period of time during which plasma concentration is greater than or equal to half the maximum) than that of Madopar capsules "125" and tablets of Madopar "250", which indicates the continuous release of modified. The bioavailability of the drug Madopar GSS "125" is 50-70% of the bioavailability of Madopar capsules "125" and tablets of Madopar "250" and not depend on eating. Eating does not affect the levodopa Cmax, which is achieved later, after 5 h after administration of Madopar GHS "125".
Distribution
Levodopa passes through the BBB via a saturable transport system. It is not bound to plasma proteins. The volume of 57 L. the AUC for levodopa in cerebrospinal fluid is 12% of that in plasma.
The benserazide in therapeutic doses does not cross the BBB. It accumulates mainly in the kidneys, lungs, small intestine and liver.
Metabolism
Levodopa is metabolized by two main (decarboxylation and o-methylation) and two additional pathways (transamination and oxidation).
The aromatic amino acid decarboxylase converts levodopa into dopamine. The main end products of this pathway are sharing golovanyova and dihydroxyphenylalanine acid.
Catechol-o-methyl-transferase methylates levodopa with the formation of 3-o-methyldopa. T1/2 the main metabolite from plasma, 15-17 h, and in patients receiving therapeutic doses of Madopar, it is the accumulation.
Decrease peripheral decarboxylation of levodopa when administered together 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, dehydrophenylalanine acid).
In the intestinal mucosa and liver benserazide gidrauxiliruetsa with the formation of trigidroksibenzilgidrazina. This metabolite is powerful inhibitor of a decarboxylase of aromatic amino acids.
Excretion
When peripheral decarboxylase inhibition T1/2 levodopa — 1.5 h. the clearance of levodopa from plasma is about 430 ml/min.
The benserazide is almost completely eliminated by metabolism. The metabolites are excreted primarily in the urine (64%) and to a lesser extent in the feces (24%).
Pharmacokinetics in special patient groups
Patients with renal and hepatic insufficiency. Data on the pharmacokinetics of levodopa in patients with renal and hepatic insufficiency are absent.
Patients are elderly (65-78 years). At elderly patients (65-78 years) with Parkinson's disease T1/2 and AUC of levodopa is increased by 25%, which is not clinically significant change and does not affect the dosing regimen.
Description pharmacological action:
Combined means for the treatment of Parkinson's disease and syndrome of "restless legs".
Parkinson's Disease. Dopamine is a neurotransmitter in the brain, is formed in the basal ganglia in patients with parkinsonism in insufficient quantities. Levodopa or L-DOPA (3,4-dehydrophenylalanine) is the metabolic precursor of dopamine. Unlike dopamine, levodopa penetrates well through the BBB. Once levodopa enters the CNS, it is converted into dopamine by means of decarboxylase of aromatic amino acids.
Substitution therapy is conducted by appointment levodopa, the immediate metabolic precursor of dopamine, since the latter does not penetrate the GEB.
After intake of rapidly decarboxylases levodopa into dopamine in cerebral and extracerebral tissues. As a result, most of the administered levodopa reaches the basal ganglia, and peripheral dopamine often causes side effects. Therefore, it is necessary to block extracerebral decarboxylation of levodopa. What is achieved by the simultaneous introduction of levodopa and benserazide inhibitor of peripheral decarboxylase.
Madopar is a combination of these substances in the optimal 4:1 ratio and has the same efficiency as large doses of levodopa.
Syndrome "restless legs". The exact mechanism of action is unknown, but dopaminergic system plays an important role in the pathogenesis of this syndrome.
Indications:
Parkinson's disease:
- Fast acting madopar tablets (dispersible) "125" — special dosage form for patients with dysphagia and akinesia in the early morning hours and in the afternoon, or when phenomena of "depletion of the effect of single dose" or "increasing the latent period before the onset of the clinical effect of the drug"
- Madopar GSS "125" is indicated for all types of hesitation of the action of levodopa (i.e. "peak dose dyskinesia" and "the phenomenon of end of dose" - for example, immobility during the night)
syndrome "restless legs", including idiopathic syndrome and the syndrome of "restless legs" in patients with chronic renal insufficiency undergoing dialysis.
Contraindications:
hypersensitivity to levodopa, benserazide or any component of the drug
decompensated dysfunction of endocrine organs, liver, or kidneys (with the exception of patients with the syndrome of "restless legs", receiving dialysis)
cardiovascular disease 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 inhibitors of MAO-A and MAO-b
age younger than 25 years
pregnancy
the breast-feeding period
women of childbearing age not using reliable methods of contraception (see "Pregnancy and lactation").
Application of pregnancy and breast-feeding:
Madopar is absolutely contraindicated in pregnancy and women of childbearing age not using reliable methods of contraception, due to possible disorders of skeletal development in the fetus.
If the background of treatment there is a pregnancy, the drug must cancel, in accordance with the recommendations of a physician.
If necessary, the drug Madopar in the period of lactation should stop breast-feeding due to the lack of reliable data on the penetration of benserazide in breast milk. We cannot exclude the risk of improper skeletal development in the newborn.
Side effects:
From blood system: rare cases of hemolytic anemia, transient leukopenia, thrombocytopenia. In patients receiving long-term levodopa it is recommended to periodically monitor the blood count, liver function and kidney.
Gastrointestinal: anorexia, nausea, vomiting, diarrhea, isolated cases of loss or change of taste, dryness of the oral mucosa.
The skin: rarely — itching, rash.
From the side of cardiovascular system: arrhythmia, orthostatic hypotension (diminished after reducing the dose Madopara), hypertension.
From the nervous system and psychic sphere: agitation, anxiety, insomnia, hallucinations, delirium, temporary disorientation (especially in elderly patients and patients who have observed these symptoms in history), depression, headache, dizziness, in the later stages of treatment sometimes — spontaneous movements (such as chorea or atetoz), episodes of "freezing", the weakening effect by the end of the period of dose (the phenomenon of "exhaustion"), the phenomenon of "on-off", severe drowsiness, episodes of sudden sleepiness, the increasing incidence of the syndrome "restless legs".
From the body as a whole: febrile infection, rhinitis, bronchitis.
The laboratory parameters: sometimes — transient increase in liver transaminases and alkaline phosphatase, increase in urea nitrogen of the blood, change the color of urine to red, darkening upon standing.
Drug interactions:
Pharmacokinetic interaction
Trihexyphenidyl (anticholinergic medication) reduces the rate but not the extent of absorption of levodopa. The appointment of trigexifenidila with Modparam GHS "125" it does not affect other pharmacokinetic parameters of levodopa.
Antacids reduce the extent of levodopa absorption by 32% in the appointment with Modparam GHS "125".
Ferrous sulfate reduces Cmax and AUC of levodopa in plasma by 30-50%, which is a clinically significant change in some patients.
Metoclopramide increases the rate of absorption of levodopa.
Levodopa does not enter into the pharmacokinetic interaction with bromocryptine, amantadine, selegiline, and domperidone.
Pharmacodynamic interaction
Neuroleptics, opioids and antihypertensive medications containing reserpine inhibit the action of Madopar.
MAO inhibitors. If Madopar is prescribed to patients receiving non-selective irreversible MAO inhibitors, discontinuation of MAO inhibitor before you start taking Madopar must be at least 2 weeks (see "Contraindications"). However, a selective MAO inhibitors (like selegiline or rasagiline) and selective inhibitors of MAO-A (such as moclobemide) can be assigned to patients taking Madopar. It is recommended to correct a levodopa dose depending on individual patient's needs in terms of efficacy and tolerability. The combination of the inhibitors of MAO-A and MAO-b is equivalent to receiving nonselective MAO inhibitor, therefore this combination should not be administered concurrently with Modparam.
Sympathomimetic (epinephrine, norepinephrine, isoproterenol, amphetamine). Madopar should not be administered concurrently with sympathomimetic agents, as levodopa may potentiate their action. If concomitant use is still mandatory, is very important to carefully control the state of the cardiovascular system and, if necessary, a dose reduction of the sympathomimetic.
Antiparkinsonian funds. Perhaps a combination of the drug with other antiparkinsonian agents (anticholinergics, amantadine, dopamine agonists), but it can enhance not only desirable but also undesirable effects. You may need to decrease the dose of Madopar or the other drug. If treatment for add is an inhibitor of catechol-o-methyltransferase /COMT/, you may need to decrease the dose of Madopar. At the beginning of therapy Modparam anticholinergic drugs should not be abolished abruptly, since levodopa is not effective immediately.
Levodopa can affect results of laboratory definition of catecholamines, creatinine, uric acid and glucose, possible false positive sample Kumbsa.
Patients receiving Madopar, the drug simultaneously with protein-rich food can disrupt the absorption of levodopa from the gastrointestinal tract.
General anesthesia with halothane. Welcome Madopara should be abolished for 12-48 h before operational intervention as the patient, receiving Madopar, during galotanovogo narcosis may experience fluctuations AD and arrhythmia.
Method of application and dose:
Inside, at least 30 minutes before or 1 hour after a meal.
Capsules (Madopar "125" or Madopar GSS "125") should be swallowed whole, without chewing. Capsules Madopar GHS "125" it is impossible to open before use, otherwise the effect of modified release of the active substance is lost.
Tablets (Madopar "250") may be crushed for easier swallowing.
Dispersible tablets (Madopar fast-acting tablets (dispersible) "125") must be dissolved in 1/4 Cup water (25-50 ml) tablet dissolves completely in a few minutes with formation of a suspension milky-white color, which should be taken no later than 30 minutes after dissolution of the tablet. As quickly, a precipitate may form before you accept the solution it is recommended to mix.
Parkinson's Disease
The standard dosing regimen
Treatment should begin gradually, individually selecting dose to the optimum effect.
Initial therapy
In the early stages of Parkinson's disease, it is recommended to start treatment with Modparam receive 62.5 mg (50 mg levodopa + 12.5 mg benserazide) 3-4 times a day. If portability of the scheme initial dosing, the dose should be slowly increased depending on patient response.
Optimal effect is usually achieved at a daily dose of 300-800 mg levodopa + 75-200 mg benserazida taken 3 or more receptions. To achieve the optimal effect may take 4 to 6 weeks. If necessary, a further increase in the daily dose of this should be done within 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 receptions (at least 3) and their distribution throughout the day should provide optimal effect.
To optimize the effect, you can replace the capsule Madopar "125" and tablets of Madopar "250" fast acting Madopar tablets (dispersible) capsule or Madopar GHS "125".
Syndrome "restless legs"
The maximum permissible dose of 500 mg/day Madopar (400 mg levodopa + 100 mg benserazida). For 1 h before bedtime, with a small amount of food.
Idiopathic syndrome "restless legs" violations of falling asleep
It is recommended to assign capsules Madopar "125" or tablets Madopar "250".
Initial dose: 62.5 mg (50 mg levodopa + 12.5 mg benserazide)-125 mg (100 mg levodopa + 25 mg benserazide) to Madopar. In case of insufficient effect increase the dose to 250 mg (200 mg levodopa + 50 mg benserazide) to Madopar.
Idiopathic syndrome "restless legs" impaired sleep and sleep
Initial dose: 1 caps. Madopar GSS "125" and 1 caps. Madopar "125" for 1 hour before sleep. At insufficient effect it is recommended to increase the dose Madopara GHS "125" 250 mg (2 caps.).
Idiopathic syndrome "restless legs" impaired sleep and sleep and disorders during the day
Optional: 1 table. dispersible or 1 caps. Madopar "125", maximum daily dose of 500 mg (400 mg levodopa + 100 mg benserazida).
Syndrome "restless legs" in patients with chronic renal insufficiency receiving dialysis
Madopar 125 mg (1 table. dispersible or 1 caps. Madopar "125") for 30 min before the initiation of dialysis.
Dosing in special cases
Parkinson's Disease
Madopar can be combined with other antiparkinsonian agents, as further treatment may be necessary to reduce the dose of other drugs or their gradual abolition.
Fast acting madopar tablets (dispersible) "125" — special dosage form for patients with dysphagia or akinesia in the early morning hours and in the afternoon, or when phenomena of "depletion of the effect of single dose" or "increasing the latent period before the onset of the clinical effect of the drug".
If during the day the patient there is a pronounced motor fluctuations (the phenomenon of "depletion of the effect of a single dose" phenomenon "on-off"), recommended a more frequent reception of correspondingly smaller doses, or — better still — use Madopara GHS "125".
The transition to Madopar GHS "125" it is best to start with the morning dose, keeping the daily dose and dosage regimen of Madopara "125" or Madopar "250".
After 2-3 days, gradually increase the dose by about 50%. The patient should be warned that his condition may temporarily deteriorate. Because of their pharmacological properties Madopar GSS "125" begins to act later. Clinical effect can be achieved faster by assigning Madopar GSS "125" together with capsules Madopar "125", or dispersible tablets. This can be especially useful in the case of the first morning dose, which should be slightly higher than the next. Individual dose Madopara GHS "125" it is necessary to pick up slowly and carefully, and the interval between changes in dose should be at least 2-3 days.
Patients with night symptoms were positive effect was achieved by gradually increasing the evening dose Madopara GHS "125" 250 mg (2 caps.) before going to sleep.
To correct a pronounced effect Madopar GSS "125" (dyskinesia) more efficiently increase the intervals between doses than the decrease dose.
If Madopar GSS "125" sufficiently effective even at a daily dose corresponding to 1500 mg of levodopa, it is recommended to return to previous treatment with Madopar "125", Madopar "250" and a fast acting Madopar tablets (dispersible) "125".
In patients with renal insufficiency mild or moderate severity dose adjustment is not required.
Madopar is well tolerated by patients, receiving hemodialysis sessions.
With long-term therapy may cause episodes of "freezing", "the phenomenon of depletion" phenomenon "on-off". In the episodes "pour point" and "the phenomenon of depletion" is used to crushing the dose (reduce dose or decrease interval between doses of the drug), and the emergence of the phenomenon of "on-off" — increase dose by reducing the number of techniques. Later you can try again to increase the dose to enhance the effect of the treatment.
Syndrome "restless legs"
To prevent the onset of symptoms of syndrome of "restless legs" (early appearance during the day, increased severity and the 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 benserazida) to Madopar.
With an increase of clinical symptoms should reduce the dose of levodopa or levodopa gradually lift and to appoint other therapy.
Overdose:
Symptoms: cardiovascular system — arrhythmias mental sphere — the mental confusion, insomnia gastrointestinal — nausea and vomiting pathological involuntary movements (mentioned in the section "Side effects", but in more severe form).
If capsules are modified-release (Madopar GSS "125") symptoms of an overdose may occur later due to delayed absorption of the active substances in the stomach.
Treatment: it is necessary to monitor vital functions, symptomatic therapy — the appointment of respiratory analeptics, antiarrhythmic drugs, in appropriate doses.
In the application of dosage forms with modified release of active substances (Madopar GSS "125") should be to prevent further drug absorption.
Special instructions:
In persons with hypersensitivity to the drug may develop appropriate responses.
Patients with open-angle glaucoma it is recommended to regularly measure the intraocular pressure, as theoretically, levodopa may increase intraocular pressure.
Side effects from the gastrointestinal tract, possible at the initial stage of treatment, can largely be eliminated, if taking Madopar with a small amount of food or liquid, and if you increase the dose slowly.
During treatment necessary to monitor liver function and kidney function, blood formula.
Patients with diabetes must frequently monitor the level of glucose in the blood and adjust the dose of hypoglycemic drugs.
If necessary, surgery with General anesthesia Modparam therapy should be continued until surgery, with the exception of General anesthesia with halothane. Because the patient, receiving Madopar, during galotanovogo narcosis may experience fluctuations AD and arrhythmia, welcome Madopara should be abolished for 12-48 h before operational intervention. After surgery resume treatment, gradually increasing the dose to the previous level.
Madopar cannot be canceled abruptly. Abrupt withdrawal of the drug can cause "neuroleptic malignant syndrome" (fever, muscle rigidity, and possible mental changes and increased serum creatine phosphokinase), which can be a life-threatening form. In the event of such symptoms, the patient should be under medical supervision (if necessary, need to be hospitalized) and to receive the corresponding symptomatic therapy. It may include redesignation Madopar after evaluation of the patient's condition.
Depression can be a clinical manifestation of the underlying disease (parkinsonism, a syndrome of "restless legs"), and arise on the background of therapy Modparam. The patient should be carefully monitored in terms of the possible occurrence of psychiatric adverse reactions.
The possibility of drug dependence and abuse
Some patients with Parkinson's disease marked the emergence of behavioral and cognitive disorders due to uncontrolled application of increasing doses of the drug, despite the recommendations of the doctor and a significant excess of therapeutic doses of the drug.
The effect on driving vehicles and working with machinery and mechanisms
If you experience drowsiness, including sudden episodes of sleepiness, should abandon driving or working with machines and mechanisms. If you encounter these symptoms, consider dose reduction or discontinuation of therapy.
