Stalevo - Instructions For Use, Price, Reviews Of Tablets, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Stalevo

Stalevo: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Drug interactions
14. 14. Analogs
15. 15. Terms and conditions of storage
16. 16. Terms of dispensing from pharmacies
17. 17. Reviews
18. 18. Price in pharmacies

Latin name: Stalevo

ATX code: N04BA03

Active ingredients: Levodopa + Entacapone + Carbidopa (Levodopa + Entacapone + Carbidopa)

Producer: Orion Corporation Orion Pharma (Finland)

Description and photo update: 2020-01-03

Prices in pharmacies: from 2959 rubles.

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Stalevo is a combined antiparkinsonian drug (dopamine precursor + peripheral decarboxylase inhibitor + catechol-O-methyltransferase inhibitor).

Release form and composition

Dosage form Stalevo - film-coated tablets: dark grayish-red or brownish-red color, without risks, with an embossing on one side: at a dosage of 50 mg / 12.5 mg / 200 mg - round biconvex tablets, code " LCE 50 "; at a dosage of 100 mg / 25 mg / 200 mg - oval tablets, code "LCE 100"; at a dosage of 150 mg / 37.5 mg / 200 mg - oblong-ellipsoidal tablets, code "LCE 150"; in a dosage of 200 mg / 54.1 mg / 200 mg - oblong, ellipsoidal, biconvex tablets, code "LCE 200" (in vials of 10, 30, 100 or 250 tablets with a dosage of 50 mg / 12.5 mg / 200 mg, 100 mg / 25 mg / 200 mg, 150 mg / 37.5 mg / 200 mg, or 10, 30, 100, 130 or 175 tablets at a dosage of 200 mg / 54.1 mg / 200 mg; in a pack of cardboard 1 bottle and instructions for use of Stalevo).

Composition for 1 tablet at a dosage of 50 mg / 12.5 mg / 200 mg, 100 mg / 25 mg / 200 mg, 150 mg / 37.5 mg / 200 mg or 200 mg / 54.1 mg / 200 mg, respectively:

• active substances: levodopa - 50; 100; 150 or 200 mg; carbidopa monohydrate - 13.5 mg; 27 mg; 40.5 mg or 54.1 mg (in terms of carbidopa 12.5 mg; 25 mg; 37.5 mg or 50 mg; entacapone (for all dosages) - 200 mg;
• auxiliary components: magnesium stearate, povidone K-30, sodium croscarmellose, mannitol, corn starch;
• film shell: glycerin 85% (glycerol 85%); polysorbate 80, magnesium stearate, iron oxide red, iron oxide yellow, titanium dioxide, sucrose, hypromellose (200 mg / 54.1 mg / 200 mg tablet coating does not contain the iron oxide yellow dye).

Pharmacological properties

Pharmacodynamics

In accordance with modern concepts, the manifestations of Parkinson's disease are associated with depletion of dopamine in the striatum. Dopamine does not cross the blood-brain barrier, and its precursor, levodopa, crosses the blood-brain barrier and relieves signs of pathology.

Since levodopa is actively metabolized in peripheral organs, when used without inhibitors of metabolic enzymes, only a small part of the prescribed dose reaches the central nervous system.

Carbidopa is a peripheral DOPA decarboxylase inhibitor that decreases the metabolism of levodopa. At the same time, dopamine is formed in the peripheral organs, which becomes more accessible to the brain. Decarboxylation of levodopa is reduced when it is used in combination with a DOPA-decarboxylase inhibitor, so it can be prescribed in lower doses, which reduces the incidence of adverse events, for example, nausea.

Against the background of suppression of decarboxylase by a DOPA-decarboxylase inhibitor, catechol-O-methyltransferase becomes the most important peripheral metabolic enzyme. It catalyzes the conversion of levodopa to its potentially harmful metabolite, 3-O-methyldopa.

Entacapone is a specific, reversible and mainly peripheral inhibitor of catechol-O-methyltransferase. It is intended for combined use with levodopa, slowing its clearance from the bloodstream, which increases the area under the concentration-time curve, which characterizes the pharmacokinetic profile of levodopa. Because of this, the clinical response to each dose of the latter is prolonged and enhanced.

Pharmacokinetics

The absorption of entacapone, levodopa and carbidopa is characterized by significant intra- and intervariability of individual values. Entacapone and levodopa undergo rapid absorption and excretion, while carbidopa is absorbed and excreted somewhat more slowly. The bioavailability of levodopa when used separately without the other two active ingredients of Stalevo varies from 15 to 33%. The bioavailability of carbidopa is from 40 to 70%, and entacapone at a dose of 200 mg is 35%.

Foods high in neutral amino acids may delay and reduce the absorption of levodopa. The regimen and diet do not affect the absorption of entacapone.

There are no data on the volume of distribution of carbidopa. The volumes of distribution of levodopa and entacapone are quite low, they are, respectively, 0.36-1.6 liters per 1 kg and 27 liters per 1 kg.

The connection with blood plasma proteins of levodopa is minimal (from 10 to 30%), while for carbidopa this figure is almost 36%. Entacapone binds to plasma proteins extensively, almost 98%, mainly with serum albumin. At therapeutic concentrations, entacapone does not displace other active components extensively associated with protein (for example, diazepam, phenylbutazone, salicylic acid or warfarin). At the same time, it is not displaced by these substances when they are used in therapeutic doses or higher concentrations.

Levodopa metabolism is active. In this case, various metabolites are formed. The most important pathways are O-methylation with catechol-O-methyltransferase and decarboxylation with DOPA decarboxylase.

The metabolism of carbidopa takes place with the formation of two metabolites, which are excreted in the urine in the form of unconjugated substances and glucuronides. From the total excretion of carbidopa in the urine, its excretion in unchanged form is 30%.

Entacapone is almost completely metabolized before excretion in the urine (10–20%) and feces / bile (80–90%). The main metabolic pathway is glucuronidation of both entacapone and its active metabolite (cis isomer). The content of the latter in blood plasma is approximately 5% of the total entacapone. The total clearance of entacapone is 0.7 liters per 1 kg per hour, for levodopa - from 0.55 to 1.38 liters per 1 kg per hour. The half-life (when taken separately): entacapone is from 0.4 to 0, 7 hours; carbidopes - from 2 to 3 hours; levodopa - from 0.6 to 1.3 tsp.

Since entacapone and levodopa have a short half-life, there is no true accumulation with repeated doses.

According to in vitro studies using microsomal preparations of human liver, entacapone inhibits cytochrome P450 2C9 enzymes (PK50 ~ 4 μM). Other isoenzymes of cytochrome P450 (CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP3A and CYP2C19) entacapone weakly inhibits or does not interact with them at all.

Levodopa therapy in elderly patients without entacapone and carbidopa increases its absorption, and slows its excretion, in comparison with younger patients. However, with the combined treatment with levodopa and carbidopa, the absorption of the first in the body of elderly and younger patients is carried out in a similar way, although in elderly subjects the area under the concentration-time curve is 1.5 times higher than that in young patients. This is due to a decrease in DOPA decarboxylase activity and levodopa clearance with age. There were no significant differences in the area under the concentration-time curve of entacapone or carbidopa in elderly (65 to 75 years old) and younger (45 to 64 years old) subjects.

In the body of men, the bioavailability of levodopa is significantly lower than in women. In pharmacokinetic studies of Stalevo, the bioavailability of levodopa in men was lower than in women, mainly due to the difference in weight, while there were no gender differences in the bioavailability of entacapone and carbidopa.

With mild to moderate hepatic failure (according to Child-Pugh classification - class A and B), entacapone metabolism slows down, which is accompanied by an increase in its content in plasma at the stage of absorption and excretion. Special studies of the pharmacokinetics of levodopa and carbidopa in liver failure have not been conducted, however, Stalevo must be used with caution in patients with mild to moderate hepatic failure.

The pharmacokinetics of entacapone in the presence of renal failure does not change. Special studies of the pharmacokinetics of levodopa and carbidopa in renal failure have not been carried out, however, it is recommended to consider the feasibility of increasing the interval between doses when prescribing the drug to patients on dialysis.

Indications for use

Stalevo is prescribed for the treatment of Parkinson's disease and parkinsonism in cases where the use of a combination of levodopa with carbidopa is ineffective. An exception is drug parkinsonism.

Contraindications

Absolute:

• angle-closure glaucoma;
• severe liver failure;
• neuroleptic malignant syndrome and / or nontraumatic rhabdomyolysis in history;
• pheochromocytoma;
• glucose-galactose malabsorption, fructose intolerance, sucrase / isomaltase deficiency;
• simultaneous administration with selective inhibitors of monoamine oxidase-A and selective inhibitors of monoamine oxidase-B;
• pregnancy (with the exception of individual situations where the expected therapeutic effect for the mother outweighs the potential risk for fetal development);
• period of breastfeeding;
• children under the age of 18;
• individual intolerance to the components of the drug.

Relative (Stalevo tablets are used under medical supervision):

• kidney and liver diseases;
• severe pulmonary and cardiovascular insufficiency;
• bronchial asthma;
• a history of convulsions;
• diabetes mellitus and other decompensated endocrine pathologies;
• erosive and ulcerative lesions of the gastrointestinal tract;
• a history of myocardial infarction with residual ventricular or atrial (atrial) nodal arrhythmias (throughout the entire period of initial regulation of the dosage regimen of the drug, it is necessary to monitor cardiac function);
• antisocial behavior, depression with suicidal tendencies, a history of psychosis or that occurred during the period of taking Stalevo;
• open-angle glaucoma (careful monitoring of intraocular pressure is required);
• simultaneous use with antipsychotics that block dopamine receptors, especially D2 receptors (therapy should be carried out under close medical supervision in order to stop the antiparkinsonian effect of the drug or enhance the manifestations of pathology);
• combination therapy with drugs metabolized by catechol-O-methyltransferase (paroxetine), warfarin, venlafaxine, maprolitine, desipramine, tricyclic antidepressants, substances that can cause orthostatic hypotension.

Stalevo, instructions for use: method and dosage

Stalevo tablets are taken orally, regardless of the diet. They cannot be broken or divided into pieces.

Through careful selection, on an individual basis for each patient, the optimal daily dose of the drug is established.

It is recommended to take only 1 tablet at any dosage as a single dose. The maximum daily dose of the active components of the drug is: levodopa - 1500 mg; entacapone - 2000 mg; carbidopa - 375 mg (equivalent to 7 Stalevo tablets with a dosage of 200 mg / 200 mg / 50 mg).

Patients receiving entacapone and levodopa / carbidopa in standard release dosage forms in doses corresponding to those in Stalevo tablets can be immediately switched to the drug in the appropriate dosage. For example, when taking 1 tablet of carbidopa / levodopa 50 mg / 200 mg and 1 tablet of entacapone 200 mg 4 times a day, it is possible to transfer the patient to the use of 1 tablet of a drug with a dose of 200 mg / 200 mg / 50 mg 4 times a day. day.

If the patient takes entacapone and levodopa / carbidopa in doses not equivalent to those for the active ingredients of Stalevo 200 mg / 200 mg / 50 mg (50 mg / 12.5 mg / 200 mg, 100 mg / 25 mg / 200 mg or 150 mg / 37.5 mg / 200 mg), the dose of the latter must be carefully titrated to obtain an optimal clinical response. Initially, it is adjusted in such a way as to achieve the maximum correspondence to the previously used daily dose of levodopa.

In cases of previous administration of entacapone and levodopa / benserazide in standard-release dosage forms, the use of levodopa / benserazide should be canceled the night before. It is necessary to initiate the use of Stalevo the next morning, starting with tablets, which contain a similar amount of levodopa or more by 5-10%.

In cases where the use of a combination of levodopa with a DOPA decarboxylase inhibitor is ineffective, the possibility of using Stalevo in appropriate doses in some patients with Parkinson's disease and motor fluctuations at the end of the dose may be considered. However, direct transfer of patients with dyskinesias (or using levodopa in a daily dose exceeding 800 mg) from a combination of levodopa with a DOPA-decarboxylase inhibitor to the drug is not recommended. In such patients, separate therapy with entacapone (in the form of tablets) should be carried out and the dose of levodopa should be adjusted before switching to the drug (if necessary).

The effect of levodopa is enhanced in the presence of entacapone, and therefore may require (especially with dyskinesias) a decrease in its dose by 10-30% in the first few days or weeks at the beginning of Stalevo therapy.

A decrease in the daily dose of levodopa can be achieved by lengthening the interval between taking the pills and / or reducing a single proportion of the substance, in accordance with the clinical condition of the patient.

If it is necessary to use a higher dose of levodopa, increase the frequency of use and / or prescribe a different dosage of the drug containing it in the recommended dose range. If, on the contrary, lower doses of levodopa are required, the total daily dose of the substance is reduced by decreasing the frequency of its administration or decreasing the dosage.

With the combined use of Stalevo with other levodopa drugs, it is important not to exceed the maximum daily dose.

If the drug is discontinued and the patient is transferred to therapy with a combination of levodopa with a DOPA-decarboxylase inhibitor without entacapone, the dose of anti-Parkinsonian drugs, in particular levodopa, should be adjusted to adequately control the manifestations of parkinsonism.

Correction of the dosage regimen in elderly patients is not carried out.

It is important to be careful when using the drug for mild to moderate hepatic impairment. In such cases, a lower dose may be required.

The pharmacokinetics of entacapone is independent of renal failure. Since no special studies of the pharmacokinetics of carbidopa and levodopa in renal failure have been carried out, the antiparkinsonian drug Stalevo should be administered under medical supervision to patients with severe renal failure, including patients on dialysis.

Side effects

During the period of Stalevo therapy, the development of the following undesirable phenomena is most often noted:

• dyskinesia (about 19% of cases);
• symptomatology of pathologies of the gastrointestinal tract, including diarrhea and nausea (in 12 and 15% of cases);
• pain in connective tissue and muscles, musculoskeletal pain (in 12% of cases);
• staining of urine in red-brown color (in 10% of cases).

According to the results of clinical studies of the drug or taking entacapone with a combination of levodopa and a DOPA-decarboxylase inhibitor, serious side effects such as Quincke's edema (rare) and gastrointestinal bleeding (infrequent) were noted.

Despite the lack of evidence from the results of clinical studies, during Stalevo therapy, malignant neuroleptic syndrome, rhabdomyolysis, and severe forms of hepatitis, often cholestatic, may appear.

Possible adverse reactions [more than 10% - very common; (> 1% and 0.1% and 0.01% and <0.1%) - rarely; (<0.01%, including isolated reports) - very rare], compiled from pooled data from 11 double-blind clinical trials (3230 volunteers participated in them) and post-marketing observations:

• blood and lymphatic system: often - anemia; infrequently - thrombocytopenia;
• metabolism and nutrition: often - decreased appetite ¹, weight loss ¹;
• psychiatric disorders: often - insomnia, anxiety, nightmares ¹, confusion ¹, hallucinations, depression; infrequently - agitation ¹, psychosis; frequency not established - suicidal behavior;
• nervous system: very often - dyskinesia ¹; often - headache, dizziness ¹, drowsiness, brain disorders (dementia, amnesia), dystonia, on-off phenomenon, tremor, exacerbation of signs of parkinsonism (for example, bradykinesia ¹); frequency not established - neuroleptic malignant syndrome ¹;
• organs of vision: often - blurred vision;
• cardiac activity: often - a violation of the heart rhythm, symptoms of ischemic heart disease, except for myocardial infarction (angina pectoris ²); infrequently - myocardial infarction ²;
• vessels: often - hypertension, orthostatic hypotension; infrequently - gastrointestinal bleeding;
• respiratory system, organs of the chest and mediastinum: often - shortness of breath;
• gastrointestinal tract: very often - nausea ¹, diarrhea ¹; often - dry mouth ¹, abdominal discomfort and pain ¹, dyspepsia, vomiting ¹, constipation ¹; infrequently - dysphagia, colitis ¹;
• hepatobiliary system: infrequently - abnormal liver function tests ¹; frequency not established - hepatitis, often cholestatic ¹;
• skin and subcutaneous fat: often - hyperhidrosis, rash ¹; infrequently - staining of sweat ¹, hair, nails and skin (except for the color of urine); rarely - Quincke's edema; frequency not established - urticaria ¹;
• skeletal muscles and connective tissue: very often - pain in muscles and connective tissue, musculoskeletal pain; often - joint pain ¹, muscle spasms; frequency not established - rhabdomyolysis ¹;
• kidneys and urinary tract: very often - chromaturia ¹; often - urinary tract infections; infrequently - urinary retention;
• general disorders and disorders at the injection site: often - fatigue, asthenia, gait disturbance, possibly accompanied by a fall, peripheral edema, chest pain; infrequently - malaise.

Notes

¹ Adverse reactions attributed to the influence of entacapone or occurring more often (according to the results of clinical studies, the difference in the incidence is 1%) during treatment with entacapone compared with therapy only with a combination of levodopa with a DOPA-decarboxylase inhibitor.

² The incidence rates of myocardial infarction - 0.43% and other heart diseases due to ischemia - 1.54%, are taken from the results of 13 double-blind studies, in which 2082 patients took part, taking entacapone for motor fluctuations associated with the end of action dose.

Some of the side effects of Stalevo are associated with increased dopaminergic activity (vomiting, dyskinesia, nausea), and usually appear at the beginning of therapy. Lower doses of levodopa reduce the degree and frequency of these dopaminergic reactions. Certain adverse events (including red-brown urine staining, diarrhea) are due to the properties of entacapone. There have been reports of staining of sweat, hair, nails and skin with entacapone.

In some cases, treatment with carbidopa in combination with levodopa is accompanied by seizures. However, a causal relationship between these phenomena has not been established.

During the period of use of dopamine agonists and / or dopaminergic drugs that include levodopa, including Stalevo, impulse control disorders such as compulsive hunger satisfaction, gluttony, urge to buy and spend money, hypersexuality, increased libido or gambling addiction may occur.

There have been isolated reports of extreme daytime sleepiness and episodes of sudden onset of sleep with the combined use of entacapone with levodopa.

Overdose

According to post-marketing data, there are reports of isolated cases of Stalevo overdose with maximum doses of levodopa and entacapone of at least 10,000 mg and 40,000 mg per day, respectively. Overdose manifestations and acute symptoms in these cases included chromaturia, staining of the conjunctiva and tongue, pallor of the skin, Cheyne-Stokes breathing, ventricular tachycardia, bradycardia, confused and agitated consciousness, coma.

The measures to be taken in case of an acute overdose of the drug are similar to those for an acute overdose of levodopa. Pyridoxine is ineffective as a drug antidote.

In such cases, hospitalization of the patient, general detoxification measures, gastric lavage and repeated use of activated carbon are important. These measures are necessary to accelerate the elimination of entacapone from the body, including by reducing the absorption / reabsorption of the substance from the gastrointestinal tract.

In turn, it is recommended to carry out procedures that maintain the normal functioning of the cardiovascular and respiratory systems, as well as the kidneys. If required, measures are taken to support these body systems. Prescribe monitoring of the electrocardiogram in order to detect arrhythmias. Antiarrhythmic therapy is started if necessary. It is important to take into account the possibility that the patient could have taken drugs other than Stalevo. The effectiveness of the use of dialysis in the treatment of overdose has not been established.

special instructions

The drug is not recommended for the treatment of drug-induced extrapyramidal reactions. It is used with caution in case of a history of convulsions, stomach ulcers, pathologies of the kidneys or the endocrine system, bronchial asthma, severe forms of pulmonary diseases or pathologies of the cardiovascular system, ischemic heart disease.

Patients who have had myocardial infarction, and have lesions of the atrial node or ventricular arrhythmias, should be assigned to monitor the work of the heart, especially when selecting the initial doses.

All patients receiving Stalevo should be carefully monitored for depression with suicidal tendencies, mental changes, and other significant antisocial reactions. The drug is used under medical supervision for psychosis (including a history).

Combined use with antipsychotics (dopamine receptor blockers, especially D2 receptor antagonists) should be used with caution. Patients are closely monitored in order to identify the loss of Stalevo's antiparkinsonian effect or worsening of the symptoms of the disease.

The drug is prescribed with caution against the background of chronic open-angle glaucoma. In these cases, careful monitoring of intraocular pressure and recording of all changes in blood pressure is necessary.

Stalevo can serve the development of orthostatic hypotension. It should be used under medical supervision in patients receiving drugs / drugs that can cause orthostatic hypotension.

Entacapone in combination with levodopa may cause episodic instant sleep and drowsiness associated with Parkinson's disease.

Clinical studies have confirmed the more frequent development of dopaminergic adverse reactions (for example, dyskinesia) when treated with amantadine, selegiline, dopamine agonists (bromocriptine), complex therapy with entacapone when compared with people who received placebo in combination with these drugs.

It may be necessary to adjust the doses of all antiparkinsonian drugs taken by the patient when prescribing the drug to patients who have not previously taken entacapone.

In rare cases, individuals with Parkinson's disease have rhabdomyolysis with dyskinesias or neuroleptic malignant syndrome. It is important to control the sudden cancellation of levodopa or a sharp decrease in its dose, especially with the combined use of antipsychotics.

Hyperthermia, rhabdomyolysis, and neuroleptic malignant syndrome are characterized by motor manifestations (tremor, myoclonus, muscle stiffness), changes in mental state (coma, confusion, agitation), autonomic dysfunctions (drops in blood pressure, tachycardia), as well as an increase in serum creatine phosphokinase concentration. There are isolated reports of the development of these symptoms and signs. Early detection of pathology is extremely important for effective treatment of neuroleptic malignant syndrome.

A condition similar to neuroleptic malignant syndrome has been reported, characterized by changes in mental health, fever, muscle rigidity, and an increase in serum creatine phosphokinase concentration, also associated with sudden withdrawal of antiparkinsonian drugs.

Of the studies conducted, in the course of which entacapone was suddenly discontinued, cases of rhabdomyolysis or neuroleptic malignant syndrome due to its cancellation were not identified. Since the advent of entacapone on the market, isolated episodes of neuroleptic malignant syndrome have been recorded, especially when the doses of it and concomitant dopaminergic drugs are reduced or when the drug is suddenly withdrawn. Based on this, if it is necessary to change the drug therapy regimen to levodopa and DOPA-decarboxylase inhibitors, it is important to carry it out gradually. An increase in levodopa dose is likely to be necessary.

When planning general anesthesia, Stalevo is used as long as the patient is allowed to take liquids and drugs inside. The resumption of the use of the drug in the previously prescribed doses is possible after general anesthesia, as soon as the patient is able to take the pills on his own.

With prolonged therapy, it is recommended to periodically monitor the functions of the kidneys and liver, as well as the cardiovascular and hematological systems.

When diarrhea occurs, it is important to monitor the patient's weight to avoid excess weight loss. Prolonged, persistent diarrhea caused by entacapone use may be a sign of colitis. Prolonged persistent diarrhea is the basis for discontinuing treatment, prescribing appropriate therapy and identifying the cause of its occurrence.

It is important to establish close observation of patients in order to identify impulse control disorders. Patients and persons involved in their treatment should be warned about the possible onset of symptoms of impulse control disorders - compulsive hunger satisfaction, gluttony, gambling addiction, hypersexuality, the desire to buy and spend money, and increased libido. These manifestations can appear during treatment with dopamine agonists and / or dopaminergic drugs, which include levodopa (including Stalevo). If such pathologies are detected, the therapy regimen should be revised.

Liver function tests and general medical examinations are required in patients with asthenia, progressive anorexia, and weight loss, especially in a relatively short time.

There may be false positive results on urine acetone test strips caused by carbidopa and levodopa. In this case, the resulting reaction does not change the boiling of the urine analysis. When checking glycosuria, a false negative result can be given by the glucose oxidase method.

Since the composition of Stalevo tablets contains sucrose, their use is contraindicated in patients with glucose-galactose malabsorption, lactose deficiency and galactose intolerance.

Influence on the ability to drive vehicles and complex mechanisms

Patients during the period of taking Stalevo should be careful when driving vehicles and conducting potentially hazardous activities, the implementation of which requires an increased concentration of attention and speed of psychomotor reactions, since the combination of levodopa, carbidopa and entacapone can cause dizziness and symptomatic orthostatic hypotension.

If the patient has episodes of instant falling asleep and / or drowsiness, he is advised to refrain from driving and performing work that requires increased attention, in order to avoid serious injury or even death (until these symptoms are eliminated).

Application during pregnancy and lactation

Stalevo is not prescribed during pregnancy / lactation.

There is no evidence of levodopa / carbidopa / entacapone therapy during pregnancy. Animal studies have revealed the toxicity of some components of the drug to the fetus. The possible risks to the human body are unknown. Stalevo is not recommended for use during pregnancy, except in cases where the benefits to the mother are higher than the possible risks to the fetus.

It is known that levodopa is excreted in breast milk, and there is also evidence that the substance suppresses lactation. Carbidopa and entacapone are excreted in animal milk, but there is no evidence that these substances are excreted in human milk. The safety of levodopa, carbidopa and entacapone for breastfed infants is unknown.

Preclinical studies of the use of entacapone, carbidopa and levodopa separately did not reveal their negative effect on the reproductive system. There have been no studies of the effect of a combination of these drugs on reproductive function in animals.

Pediatric use

Stalevo is not prescribed for children and adolescents under the age of 18, since the safety and efficacy of its use in patients of this age group has not been established.

With impaired renal function

The drug Stalevo is used with caution in patients with kidney disease.

For violations of liver function

• use is contraindicated: severe liver failure;
• the appointment requires medical supervision: liver pathology.

Drug interactions

Currently, there is no evidence of the incompatibility of Stalevo with the usual antiparkinsonian drugs. It is known that high doses of entacapone can alter the absorption of carbidopa. However, when it was used as part of the recommended therapy regimen (0.2 g of entacapone up to 10 times a day), no interaction with carbidopa was found. According to studies of the effect of multiple doses on patients with Parkinson's disease using levodopa drugs in combination with DOPA-decarboxylase inhibitors, entacapone and selegiline do not interact with each other. The dosage of selegiline for combined treatment with Stalevo should not exceed 0.01 g.

Drugs / substances, the use of which is combined with levodopa requires caution include:

• antihypertensive drugs: therapy with these drugs can lead to symptomatic orthostatic hypotension. In such cases, the dose of the antihypertensive agent is adjusted;
• antidepressants: against the background of the use of carbidopa / levodopa with tricyclic antidepressants, undesirable effects in the form of dyskinesia and hypertension may develop.

Pharmacodynamic interactions between entacapone and imipramine, as well as entacapone and moclobemide, were not identified in studies conducted on healthy volunteers.

A significant number of patients with Parkinson's disease were followed up during the use of combined preparations of levodopa, carbidopa and entacapone with various active components [norepinephrine reuptake inhibitors (venlafaxine, maprotiline, desipramine), tricyclic antidepressants, substances metabolized by methyl catechol-O- structural compounds of catechol), inhibitors of monoamine oxidase-A]. These studies did not reveal pharmacodynamic interactions, however, caution is advised when prescribing these drugs in combination with Stalevo.

The therapeutic effect of levodopa may be reduced when taken simultaneously with papaverine, phenytoin, dopamine receptor antagonists, including some antiemetics and antipsychotics. It is important to carefully monitor the condition of patients receiving such a combination for a decrease in response to therapy.

Due to the affinity between the cytochrome P450 CYP2C9 enzyme and entacapone in vitro, the drug can potentially interact with active components, the metabolism of which depends on this isoenzyme, for example, with S-warfarin. The conducted studies of the interaction of these substances in healthy volunteers did not reveal the effect of entacapone on the change in the levels of S-warfarin in the blood plasma, while the line under the "concentration-time" curve of R-warfarin increased on average by 18%. The international normalized ratio values increased by 13% on average. It is recommended to monitor this indicator in patients who receive Stalevo while being treated with warfarin.

Because levodopa competes with some amino acids, absorption of the drug may be impaired if a high protein diet is followed. Since levodopa and entacapone are capable of chelating with iron in the gastrointestinal tract, the medication with iron-containing drugs should be taken at intervals of 2 to 3 hours.

According to in vitro studies, entacapone binds to a second binding site for human albumin, which also binds other substances, including ibuprofen and diazepam. Significant shifts in therapeutic concentrations when using such combinations are unlikely. According to the current information available, such interactions have not been recorded.

Analogs

Stalevo's analogues are Confundus Trio, Madopar, Izikom, Sinemet, etc.

Terms and conditions of storage

Store in a place protected from light and moisture at temperatures up to 25 ° C. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Stalevo

The described three-component drug of a new generation has been used for the treatment of Parkinson's disease and parkinsonism since 2003, including more than 10 years in Russia. During this time, according to experts, thanks to the combined composition, which includes levodopa, carbidopa and the catechol-O-methyltransferase inhibitor entacapone, the drug has proved to be the best. It provides more stable, close to physiological, stimulation of dopamine receptors, allowing you to maintain the most uniform level of levodopa in the blood plasma.

According to the results of international controlled clinical trials, the appointment of Stalevo to patients with Parkinson's disease from the moment the first signs of early fluctuations appear increases the effectiveness of the current treatment and may have a positive effect on the subsequent course of the disease.

In addition, there are few reviews of Stalevo from patients, which also indicate its high efficiency.

Price for Stalevo in pharmacies

The approximate price for Stalevo for a package of 30 tablets, depending on the dosage, is: 100 mg / 25 mg / 200 mg - from 2982 to 3119 rubles; 150 mg / 37.5 mg / 200 mg - from 2816 to 3119 rubles; 50 mg / 12.5 mg / 200 mg - from 1753 to 3058 rubles.

Stalevo: prices in online pharmacies

Drug name Price Pharmacy

Stalevo 100 mg / 25 mg / 200 mg film-coated tablets 30 pcs. 2959 RUB Buy

Stalevo tablets p.p. 150mg + 37.5mg + 200mg 30 pcs. RUB 3089 Buy

Stalevo 150 mg / 37.5 mg / 200 mg film-coated tablets 30 pcs. RUB 3089 Buy

Stalevo 50 mg / 12.5 mg / 200 mg film-coated tablets 30 pcs. 3399 RUB Buy

Stalevo 200 mg / 200mg / 50mg film-coated tablets 30 pcs. 3670 RUB Buy

Stalevo tablets p.p. 100mg + 25mg + 200mg 30 pcs. 3761 RUB Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!