Instructions for Levocom tablets 250 mg + 25 mg blister No. 100
Composition
active ingredients: levodopa, carbidopa;
1 tablet contains levodopa 250 mg, carbidopa 25 mg;
Excipients: corn starch, pregelatinized starch, Indigo carmine dye (E 132), magnesium stearate, microcrystalline cellulose.
Dosage form
Pills.
Main physicochemical properties: blue tablets with inclusions, round shape, with a score.
Pharmacotherapeutic group
Antiparkinsonian drugs. Dopaminergic drugs. DOPA and derivatives. Levodopa with decarboxylase inhibitor. ATX code N04B A02.
Pharmacological properties
Pharmacodynamics
Levocom is a combined antiparkinsonian drug that includes levodopa, a metabolic precursor of dopamine, and a peripheral neurotransmitter inhibitor.
dopa decarboxylase – carbidopa.
The symptoms of Parkinson's disease are thought to be related to a lack of dopamine. Normally, dopamine functions as a neurotransmitter and is produced in certain brain cells that control muscle activity. The movement disorders are thought to be a result of dopamine deficiency.
The antiparkinsonian effect of levodopa is due to its conversion into dopamine by decarboxylation directly in the central nervous system (CNS), which eliminates the dopamine deficiency in nerve cells.
Carbidopa, which does not penetrate the blood-brain barrier, prevents the extracerebral decarboxylation of levodopa, thereby increasing the delivery of levodopa to the brain and its conversion to dopamine in the CNS, which helps reduce the symptoms of Parkinson's disease in many patients.
Pharmacokinetics
Levodopa is rapidly absorbed from the gastrointestinal tract and metabolized. It is mainly converted to dopamine, adrenaline and noradrenaline and ultimately to hydroxyphenylacetic, homovanillic and vanillylmandelic acids. 3-O-methyldopa is found in blood plasma and cerebrospinal fluid. The half-life of levodopa from blood plasma is approximately 50 minutes. With the combined use of carbidopa and levodopa, the half-life of levodopa increases to 1.5 hours. All metabolites of carbidopa and levodopa are excreted in the urine.
Indication
Parkinson's disease. Parkinson's syndrome.
Contraindication
Known hypersensitivity to any of the components of the drug.
Concomitant use of non-selective monoamine oxidase (MAO) inhibitors (these drugs should be discontinued at least 2 weeks before starting treatment with Levok). The drug can only be used with selective MAO-B inhibitors at recommended doses (e.g. selegiline HCl).
Severe psychoses.
Severe hepatic and renal insufficiency. Severe heart failure. Severe cardiac arrhythmia. Acute stroke. Conditions in which adrenergic agents are contraindicated (e.g. pheochromocytoma, hyperthyroidism, Cushing's syndrome). Suspicious undiagnosed skin lesions (dermatoses) or history of melanoma. Angle-closure glaucoma.
Interaction with other medicinal products and other types of interactions
Caution should be exercised when using Levocom with other medications.
Antihypertensive drugs.
When used simultaneously with some antihypertensive agents, levodopa/carbidopa may cause symptoms of orthostatic hypotension, which requires dose adjustment of antihypertensive agents at the beginning of treatment with the drug.
Antidepressants.
Adverse reactions, including hypertension and dyskinesia, are possible when levodopa/carbidopa is co-administered with tricyclic antidepressants. Levocom should only be used under supervision with selective MAO-B inhibitors at recommended doses (e.g., selegiline HCl).
Anticholinergic drugs.
May act synergistically with levodopa to reduce tremor, but may increase uncontrolled movements. In high doses, they may also reduce the beneficial effects of levodopa by slowing its absorption.
Iron.
A decrease in the bioavailability of the active ingredients of Levocom has been recorded when used together with ferrous sulfate or ferrous gluconate.
Anesthetics.
Concomitant use of anesthetics may cause arrhythmia.
Other medicines.
Dopamine D2 receptor antagonists (e.g. phenothiazines, butyrophenones and risperidone) and isoniazid may reduce the therapeutic effect of levodopa.
The positive effect of Levocom in Parkinson's disease may be reversed by the use of phenytoin and papaverine. Therefore, patients using these drugs in combination with levodopa/carbidopa should be closely monitored due to the possibility of loss of therapeutic effect.
The use of levodopa/carbidopa with drugs that block dopamine uptake (e.g., tetrabenazine) or with other drugs that may suppress monoamine levels is not recommended.
Concomitant therapy with selegiline may lead to severe orthostatic hypotension, which is not typical for Levocom.
The effect on the bioavailability of levodopa has not been studied when used simultaneously with antacids.
It is possible to use Levocom simultaneously with products containing vitamin B6 (pyridoxine hydrochloride).
Application features
The drug should not be used to treat extrapyramidal reactions caused by medication.
Patients previously treated with levodopa as monotherapy may be treated with Levocom. However, levodopa should be discontinued at least 12 hours before starting Levocom. The daily dose should provide approximately 20% of the previous daily levodopa dose (see section 4.2).
Melanoma. Epidemiological studies have shown that patients with Parkinson's disease have an increased risk (approximately 2-6 times) of developing melanoma. However, it is not known whether the increased risk of melanoma is due to Parkinson's disease or to other factors, such as the use of medications prescribed for the treatment of Parkinson's disease. Therefore, regular skin monitoring is recommended when using Levocom. Ideally, periodic skin examinations should be performed by qualified specialists (e.g. dermatologists).
Dopamine dysregulation syndrome (DDS) is an addictive disorder resulting from excessive drug use and has been observed in some patients taking carbidopa/levodopa. Before starting treatment, patients and their caregivers should be warned about the potential risk of developing DDS (see also section “Adverse reactions”).
Impulse control disorders.
Patients should be closely monitored for the development of impulse control disorders. Patients and their caregivers should be warned about possible changes in behavior that indicate impulse control disorders, such as pathological gambling, increased libido, hypersexuality, impulsive buying, binge eating, impulsive eating, when using dopamine agonists and/or dopaminergic treatment, including Levocom. In this case, the treatment should be adjusted.
Dyskinesia may occur in patients previously treated with levodopa alone, as carbidopa improves the transport of levodopa into the brain tissue, resulting in increased dopamine production. If dyskinesia occurs, a dose reduction may be necessary.
Levocom, like other levodopa preparations, may cause involuntary movements and mental disorders. These reactions are probably due to an increase in dopamine concentration in the brain after levodopa administration. A dose reduction may be necessary.
Patients should be closely monitored for the development of depression with concomitant suicidal thoughts. Patients with psychosis (including a history) require special attention. Patients who are taking psychoactive drugs concomitantly also require special attention.
The drug should be prescribed with caution to patients with severe diseases of the cardiovascular system and lungs, bronchial asthma, diseases of the kidneys, liver and endocrine system, with peptic ulcer (due to the risk of bleeding in the upper intestinal tract) or seizures in history. Levok is also prescribed with caution to patients who have recently suffered a myocardial infarction, in the presence of atrial, nodal or ventricular arrhythmia. It is necessary to monitor the condition of the cardiovascular system of such patients, especially during the initial dose of the drug.
Patients with chronic open-angle glaucoma should be prescribed the drug with caution, subject to constant monitoring of intraocular pressure and careful observation of its changes during treatment.
A complex of symptoms similar to neuroleptic malignant syndrome has been observed with abrupt withdrawal of the drug, with manifestations of muscle rigidity, hyperthermia, mental changes and increased serum creatine phosphokinase levels. Careful monitoring of the condition of patients who are being reduced in dose or discontinued is necessary, especially if the patient is taking neuroleptics at the same time.
Levodopa may cause drowsiness and sudden sleep onset. Sudden onset of sleep onset during daytime activities is rare. However, patients should be advised of the possibility of such symptoms and consideration should be given to reducing the dose or discontinuing treatment if they occur.
During long-term treatment, it is necessary to periodically monitor the functional state of the liver, kidneys, cardiovascular system and hematopoietic system.
If surgery is required under general anesthesia, the drug should be discontinued the day before. The drug should be resumed after surgery as soon as the patient is able to take it.
Carbidopa and levodopa preparations may cause a false-positive reaction for ketone bodies in urine when using a dipstick to detect ketonuria. This reaction is not altered by boiling urine samples.
False-negative results may be obtained when using the glucose oxidase method of testing for glycosuria.
Ability to influence reaction speed when driving vehicles or other mechanisms
Considering that adverse reactions (dizziness, hallucinations, uncontrolled movements, drowsiness, sudden sleep onset, visual disturbances) may occur when using the drug, you should refrain from driving vehicles and performing other work that requires concentration of attention while taking the drug.
Use during pregnancy or breastfeeding
The effect of the drug on pregnancy is unknown, however, both levodopa and its combination with carbidopa have caused malformations of the internal organs and skeleton of the fetus in animal experiments. Therefore, the drug should not be used during pregnancy.
If it is necessary to use the drug in breastfeeding women, breastfeeding should be discontinued for the period of treatment.
Method of administration and doses
Levocom is administered orally to adults. The dosage regimen is set by the doctor individually depending on the severity of the disease, concomitant pathology and therapeutic effect for adult patients who have previously been treated with the drug. To achieve the optimal effect, it is best to take the drug daily, without taking a break in use.
Patients not receiving levodopa: For patients starting treatment with Levok, the initial dose is ½ tablet 1 or 2 times a day after meals. If necessary, the dose should be increased gradually by ½ tablet daily or every other day until the optimal therapeutic effect is obtained. Therapeutic response to the drug is observed within one day, and sometimes after a single dose. The full effective dose of the drug is achieved within 7 days compared to weeks and months of levodopa alone.
Patients receiving levodopa: Levodopa should be discontinued at least 12 hours (24 hours for slow-release) before starting Levok. The dose should be approximately 20% of the previous daily dose of levodopa.
Initial dose: For patients receiving less than 1500 mg of levodopa per day, the initial daily dose should be 75-100 mg of carbidopa and 300-400 mg of levodopa (use a drug with a dosage ratio of 1:4 carbidopa/levodopa) per
3–4 doses per day. Patients receiving more than 1500 mg of levodopa per day should start with a dose of 1 tablet 3–4 times a day.
Maintenance therapy: therapy with the combined drug Levocom should take into account the individual characteristics of patients, the dosage can be gradually changed depending on the therapeutic effect.
If a larger amount of levodopa is needed, the dose of the drug can be increased by ½ or 1 tablet each subsequent day to the maximum daily dose of 200 mg of carbidopa and 2 g of levodopa (8 tablets in 3-4 doses) for patients weighing 70 kg.
When transferring a patient from levodopa to Levocom in combination with other decarboxylase inhibitors, their use should be discontinued at least 12 hours before starting Levocom.
For patients taking other antiparkinsonian drugs concomitantly with Levok, the dose of these drugs may need to be adjusted.
The combination of the drug with MAO inhibitors type B (MAO-B) can increase the effectiveness of the drug in controlled cases of akinesia and/or dyskinesia.
Elderly patients: This drug should be used in elderly patients.
Children
The safety and effectiveness of the drug in children have not been established, so it should not be used in patients under 18 years of age.
Overdose
Precautions for Levocom overdose are the same as for levodopa overdose, however, pyridoxine is not effective in reducing the effects of Levocom.
Symptoms: involuntary movements, blepharospasm, hypertension, increased heart rate, heart rhythm disturbances, confusion, anxiety, insomnia, restlessness.
Treatment: artificially induce vomiting, emergency gastric lavage.
Symptomatic therapy: infusions should be administered with caution, attention should be paid to airway patency; if arrhythmia occurs, appropriate treatment should be applied with ECG monitoring. The value of dialysis for the treatment of overdose has not been studied.
Adverse reactions
When using levodopa/carbidopa, the most common side effects are caused by the central neuropharmacological activity of dopamine: dyskinesias (including choreic), dystonic and other involuntary movements, nausea. Muscle twitching and blepharospasm may be early signs for reducing the dose of the drug. They disappear when the dose of the drug is reduced or during treatment.
Other serious side effects include mental changes, including paranoid thinking and psychosis, depression with or without suicidal tendencies, and dementia. There have been reports of pathological excitement, increased libido, and hypersexuality among patients, especially at high doses; these symptoms resolve with dose reduction or discontinuation of therapy.
Nervous system: dyskinesia, including chorea, dystonia, bradykinesia, bradykinetic episodes ("on-off" phenomenon), (may occur several months or even years after the start of levodopa treatment and is probably associated with disease progression (in such cases, dose and interval adjustment may be necessary)), ataxia, asthenia, disorientation, numbness, blepharospasm, trismus, dizziness/vertigo, drowsiness, including very rarely - excessive daytime sleepiness and sudden episodes of falling asleep, paresthesia, syncope, dementia, hand tremor, extrapyramidal and motor disorders, impaired motor coordination, fatigue, headache, activation of latent Horner's syndrome, fainting, respiratory depression, falls, gait disturbance, irritability. Very rarely - convulsions.
Psychiatric: sleep disturbances, psychotic episodes including delusions, nightmares, hallucinations, and paranoid thinking, decreased thinking ability, depression with or without suicidal ideation, confusion, insomnia, anxiety, mental status changes including mania, impulse control disorders such as pathological gambling, increased libido, hypersexuality, possible symptoms of impulse control disorder and compulsive behavior (binge eating, oniomania (impulsive buying)) have been observed in patients receiving dopamine agonists, including carbidopa/levodopa, especially at high doses. These undesirable effects were mostly reversible upon dose reduction or discontinuation of treatment. Fear, euphoria, dopamine dysregulation syndrome.
Benign, malignant and other neoplasms (including cysts and polyps): benign, malignant and undiagnosed neoplasms, including cysts and polyps, malignant melanoma.
From the blood system: leukopenia, hemolytic and non-hemolytic anemia, thrombocytopenia, agranulocytosis.
Immune system disorders: angioedema.
Metabolic disorders: anorexia, weight gain or loss, edema.
On the part of the organs of vision: diplopia, mydriasis, oculomotor crisis (tonic spasms of the external muscles of the eyeball), blurred vision.
Cardiovascular system: heart rhythm disturbances/palpitations, orthostatic effects, including hypotension, hypertension, chest pain, phlebitis, tendency to faint, syncope, flushing, flushing.
Respiratory: shortness of breath, hoarseness, abnormal breathing, dyspnea.
On the part of the digestive tract: nausea, vomiting, diarrhea, constipation, abdominal pain, dark saliva, dyspepsia, dryness and bitter taste in the mouth, hypersalivation, dysphagia, bruxism, hiccups, gastrointestinal bleeding, flatulence, burning sensation of the tongue, development of duodenal ulcer.
Skin and subcutaneous tissue disorders: hypersensitivity reactions, including angioedema, urticaria, puritis, Henoch-Schönlein disease, hair loss, rash, dark sweat, itching, increased sweating, activation of malignant melanoma.
Musculoskeletal system: muscle cramps, muscle spasm.
From the urinary system: urinary retention, urinary incontinence, dark urine, priapism.
Others: edema, general weakness and malaise, feeling of irritation, neuroleptic malignant syndrome.
Laboratory indicators: increased liver function tests such as alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase, bilirubin, blood urea nitrogen, creatinine, uric acid, positive Coombs test.
Rarely, decreased hemoglobin and hematocrit, increased serum glucose levels, leukocytosis, bacteriuria, and hematuria were observed.
Description of some adverse reactions.
DDS is an addictive disorder that has occurred in some patients taking carbidopa/levodopa. Patients have experienced compulsive behavior as a result of drug abuse, which in some cases may have led to tardive dyskinesia.
Expiration date
3 years.
Storage conditions
Store out of the reach of children, in the original packaging at a temperature not exceeding 25 °C.
Packaging
10 tablets in a blister; 10 blisters in a cardboard pack.
Vacation category
According to the recipe.
Producer
"Pharma Start" LLC.
Location of the manufacturer and its business address
Ukraine, 03124, Kyiv, Vaclav Havel Boulevard, 8.
