Tidomet forte pills 250mg 25mg N100
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Active ingredients
Levodopa + Carbidopa
Release form
Pills
Composition
Levodopa 250 mg; carbidopa 25 mg
Pharmacological effect
Levodopa is an amino acid derived from L-tyrosine. Dopamine is formed directly from levodopa with the participation of the cytoplasmic enzyme - aromatic L-amino acid decarboxylase. The end result of the effect of dopamine is the inhibition of neuronal activity in the striatum of the brain. Levodopa is rapidly decarboxylated in peripheral tissues under the influence of pyridoxine-dependent decarboxylase aromatic L-amino acids, turning into dopamine, which, however, does not penetrate through the blood-brain barrier .; Carbidopa inhibits the process of decarboxylation of levodopa in peripheral tissues, while not penetrating the blood-brain barrier and does not affect the conversion of levodopa into dopamine in the central nervous system. Thus, the combination of carbidopa and levodopa allows you to increase the amount of levodopa entering the brain. When taken together, carbidopa doubles the bioavailability of levodopa. The introduction of carbidopa never leads to the complete inhibition of the decarboxylase of aromatic L-amino acids.
Pharmacokinetics
Levodopa; Suction; Levodopa is absorbed by active transport from the gastrointestinal tract, its passage through the blood-brain barrier is also carried out through active mechanisms. A barrier to the absorption of levodopa is the presence of aromatic L-amino acid decarboxylase in the intestinal wall. From the stomach, levodopa is absorbed in limited quantities. The rate of gastric emptying plays a key role in the absorption of levodopa. Factors that slow gastric emptying (food, M-anticholinergic drugs), delay the passage of levodopa into the duodenum and slow down its absorption. Cmax of levodopa in the blood is noted after 1-2 h after injection .; Distribution; Vd of levodopa is 0.9-1.6 l / kg. While maintaining the activity of aromatic L-amino acid decarboxylase, the total clearance of levodopa in the blood plasma is 0.5 l / kg / h. Levodopa penetrates the blood-brain barrier by facilitated diffusion. The capillary endothelium of the brain also contains aromatic L-amino acid decarboxylases as a second potential barrier to the entry of levodopa into the brain, however,in these capillaries a small part of the administered dose of levodopa is decarboxylated .; Metabolism; Approximately 70-75% of ingested levodopa is metabolized in the intestinal wall (“first pass” effect). The liver in the metabolism of the first passage practically does not accept. With increasing doses, the amount of levodopa undergoing decarboxylation in the intestine decreases. Levodopa does not bind to plasma proteins. Decarboxylation of levodopa by aromatic L-amino acid decarboxylase is the main route for the formation of dopamine from levodopa. A large amount of this enzyme is found in the intestines, liver and kidneys. The methoxylation of levodopa under the influence of catechol-O-methyltransferase to form 3-O-methyldopa is the second pathway of levodopa metabolism. With prolonged treatment, this metabolite may accumulate. Transamination is an additional pathway for levodopa metabolism. The final product of this pathway is vanilpyruvate, vanilla acetate and 2,4,5-trihydroxyphenyl acetic acid. All metabolic pathways, with the exception of transamination, are irreversible .; Withdrawal; In combination with carbidopa, T1 / 2 of levodopa is increased up to 3 hours. Up to 69% of levodopa can be detected in the urine in humans in the form of dopamine and its metabolites - vinilindoic acid, norepinephrine, homovanillic acid, dihydrophenylacetic acid; Carbidopa; does not penetrate the blood-brain barrier. Cmax in plasma is achieved in 2-4 hours. Approximately 50% of carbidopa is excreted in the urine and feces. 35% of carbidopa excreted by the kidneys is excreted unchanged.
Indications
- Parkinson's disease; - Parkinson's syndrome (post-encephalitic parkinsonism, parkinsonism due to carbon monoxide and (or) manganese intoxication).
Contraindications
- angle-closure glaucoma; - severe psychosis or neurosis; - melanoma or suspicion of it; - skin diseases of unknown etiology; - Huntington's disease; - Essential tremor; - simultaneous use of non-selective MAO inhibitors; - should not be used to treat secondary parkinsonism caused by the use of antipsychotics (neuroleptics); - not recommended for use in children under 18 years of age due to insufficient data on efficacy and safety; - hypersensitivity to any of the components of the drug .; With caution, the drug is prescribed with caution when erosive and ulcerative lesions of the stomach and / or duodenum, epileptic seizures in history,myocardial infarction with cardiac arrhythmias in history, heart failure, diseases of the endocrine system (including diabetes), bronchial asthma, mental disorders, as well as severe violations of liver and kidney function.
Use during pregnancy and lactation
The effect of the drug on the course of pregnancy in women is unknown. In experimental studies revealed that the combination of levodopa and carbidopa causes visceral and skeletal changes in animals. Therefore, the use of the drug is possible only when the expected benefit of therapy for the mother outweighs the potential risk to the fetus .; It is not known whether levodopa and carbidopa are excreted in breast milk. There is one report on the excretion of levodopa with breast milk in a nursing mother with Parkinson's disease. Therefore, due to the possible serious adverse effects of the drug on the child and taking into account the importance of conducting therapy for the mother, if you need to use the drug during lactation, you should either stop breastfeeding or stop the drug.
Dosage and administration
Inside, with a small amount of food or after food, washing down with water and not chewing. Since there is a competition between aromatic amino acids and levodopa during absorption, the consumption of large amounts of proteins should be avoided while using the drug .; The average daily dose of carbidopa needed to suppress the peripheral transformation of levodopa is 70-100 mg. Exceeding 200 mg of carbidopa does not entail a further enhancement of the therapeutic effect. The daily dose of levodopa should not exceed 2000 mg. Initial dose - 1/2 tab. 2 times / day, if necessary, can be increased by 1/2 tab. 2 times / day. As a rule, at the beginning of replacement therapy the daily dose should not exceed 3 tab./day (1 tab. 3 times / day). Use in this dose is recommended at the beginning of treatment of severe cases of parkinsonism. The daily dose of the drug as an exception may be increased with monotherapy, but should not exceed 8 tab. (1 tab. 8 times / day). Use in quantities of more than 6 tab./day should be carried out with great care .; Tidomet Forte when replacing levodopa; Levodopa is stopped 12 hours before treatment with Tidomet Forte, and in case of taking prolonged forms of levocarbidopa - 24 hours. The dose of Tidomet Forte should not exceed 20% of the previous dose of levodopa. Maintenance dose is 3-6 pills / day for most patients.
Side effects
The most common are dyskinesias, including involuntary movements (including choreiform, dystonic), as well as nausea .; The early signs on which a decision can be made to discontinue the drug are muscle twitching and blepharospasm .; Nervous system disorders: psychotic reactions, including delirium, hallucinations and paranoid thinking, neuroleptic malignant syndrome, bradykinesia episodes (on-off syndrome), agitation, paresthesia, dizziness, drowsiness, sleep disturbances, including nightmares, sleeplessness; confusion, headache, depression (including suicidal intent), dementia, pathological addictions, increased libido. It was reported about the development of seizures, but a causal relationship with taking the drug has not been established .; On the part of the digestive system: vomiting, anorexia, diarrhea, constipation, dyspepsia, dryness of the oral mucosa, change in taste, darkening of saliva, bleeding from the gastrointestinal tract, duodenal ulcer .; On the part of the cardiovascular system: arrhythmia and / or sensation of heartbeat, orthostatic reactions, including reduction or increase in blood pressure, fainting; phlebitis.; On the part of the hematopoietic system: leukopenia, thrombocytopenia, anemia (including hemolytic), agranulocytosis .; Allergic reactions: angioedema, urticaria, pruritus, hemorrhagic vasculitis (Shenlein-Genoch purpura), bullous eruptions (including reactions similar to the pemphigus) .; On the part of the respiratory system: shortness of breath, infections of the upper respiratory tract .; On the part of the skin: skin rash, excessive sweating, darkening of sweat, alopecia .; Urinary system disorders: urinary tract infections, frequent urination, darkening of urine .; Changes in laboratory parameters: decrease in hemoglobin and hematocrit, increased activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT), lactate dehydrogenase, alkaline phosphatase, hyperbilirubinemia, elevation of urea nitrogen, a positive Coombs test, hyperglycemia, leukocyte, lymphocyte, a human culture, an increase in urea nitrogen, an increase in uranium nitrogen, a positive Coombs test, hyperglycemia, leukocytemia Others: chest pain, asthenia .; The following are the other side reactions that were observed when using only levodopa, which meansthey can be noted when using the drug Tidomet Forte:; From the side of the cardiovascular system: myocardial infarction .; On the part of the digestive system: gastrointestinal pain, dysphagia, drooling, flatulence, bruxism, burning sensation of the tongue, heartburn, hiccups .; On the part of the metabolism: edema, weight loss or increase .; Nervous system disorders: ataxia, extrapyramidal disorders, falls, anxiety, gait disturbance, nervousness, decreased thinking acuity, memory loss, disorientation, euphoria, blepharospasm, trismism, tremor enhancement, torpor, muscle twitching, activation of Horner's latent syndrome, peripheral neuropathy. ; On the part of the respiratory system: pain in the pharynx, cough .; On the part of the skin: malignant melanoma, "tides" of blood .; From the senses: oculogy crisis, diplopia, blurred vision, mydriasis .; On the part of the genitourinary system: urinary retention, urinary incontinence, priapism .; Others: abdominal pain, fatigue, weakness, pain in the lower limbs, shortness of breath, indisposition, hoarseness, agitation .; On the part of laboratory parameters: leukopenia, hypokalemia, hypercreatininemia and hyperuricemia, proteinuria and glucosuria.
Overdose
Treatment: gastric lavage, careful observation and ECG monitoring for the timely detection of arrhythmias; if necessary - antiarrhythmic therapy.
Interaction with other drugs
Simultaneous use with antihypertensive drugs requires special attention due to the danger of postural hypotension .; With simultaneous use of levodopa with monoamine oxidase (MAO) inhibitors (with the exception of MAO-B inhibitors), circulatory disorders are possible (the use of MAO inhibitors should be discontinued within 2 weeks). This is due to the accumulation of dopamine and iorepinephrine under the influence of levodopa, whose metabolism is slowed down by MAO inhibitors, and a high probability of developing agitation, increasing blood pressure, tachycardia, facial flushing and dizziness .; When used together with tricyclic antidepressants, arterial hypertension and dyskinesia may occur, as well as a decrease in the bioavailability of levodopa .; When used together with D2-dopamine receptor agonists (phenothiazine derivatives, butyrophenone), as well as with isoniazid, the therapeutic effect of levodopa can be reduced .; May enhance the action of adrenomimetics, and therefore it is recommended to reduce their dose.With simultaneous use of levodopa with beta-adrenomimetics, means for inhalation anesthesia may increase the risk of developing heart rhythm disorders .; When using amantadine with levodopa, a potentiating effect is observed .; Methyldopa and levodopa can potentiate one another’s side effects .; Pyridoxine is a cofactor of the aromatic L-amino acid decarboxylase enzyme, which is responsible for the peripheral decarboxylation of levodopa and the formation of dopamine. When administered to patients receiving levodopa (without aromatic L-amino acid decarboxylase inhibitors), peripheral metabolism of levodopa is enhanced and less of it penetrates the blood-brain barrier. Thus, pyridoxine reduces the therapeutic effect of levodopa, if inhibitors of peripheral decarboxylase aromatic L-amino acids are not additionally prescribed .; With the additional appointment of aromatic L-amino acid decarboxylase inhibitors, the daily dose of levodopa can be reduced by 70-80% while maintaining the same clinical result .; When combined with diazepam, phenytoin, clonidine, derivatives of thioxanthene, papaverine, reserpine, M-anticholinergics, a decrease in anti-Parkinsonian action is possible .; With simultaneous use with lithium preparations increases the risk of dyskinesia and hallucinations .; Iron salts can reduce the bioavailability of levodopa and carbidopa; the clinical significance of this interaction is unknown .; Although metoclopramide increases the bioavailability of levodopa by accelerating gastric emptying, it can nevertheless adversely affect the control of the disease due to its antagonism with dopamine receptors.
special instructions
Should not be used in cases of secondary parkinsonism (Parkinson’s syndrome) caused by the use of antipsychotics (neuroleptics) .; It is necessary to stop treatment gradually, since with a sudden discontinuation of the drug, it is possible to develop a symptom complex resembling a malignant neuroleptic syndrome (muscle rigidity, increased body temperature, increased serum creatine phosphonokinase (CPK) activity).It is necessary to monitor patients who need to suddenly reduce the dose of the drug or stop taking it .; Levodopa absorption in older patients is higher than in younger ones. These data confirm the information about a decrease in the activity of aromatic L-amino acid decarboxylase in tissues with age, as well as with prolonged use of levodopa .; With erosive and ulcerative lesions of the stomach and / or duodenum, epileptic seizures in history, myocardial infarction with rhythm disturbances in history, heart failure, diabetes, bronchial asthma, diseases of the endocrine system, mental disorders, as well as in severe violations of the function of the liver, hepatic asthma, diseases of the endocrine system, mental disorders, as well as in severe violations of the function of the liver, hepatic asthma, diseases of the endocrine system, mental disorders, as well as in severe violations of the function of the liver, hepatic asthma, diseases of the endocrine system, mental disorders, as well as in severe violations of the function of the liver, hepatic asthma, endocrine disorders, mental disorders, as well as in severe violations of the function of the liver, liver, asthma, endocrine disorders, mental disorders, as well as in severe violations of the function of the liver, liver, asthma, endocrine disorders, mental disorders, as well as in severe disorders of the liver, hemorrhage asthma, endocrine disorders, mental disorders, as well as in severe disorders of the liver, hereditary asthma, and endocrine disorders take the drug with caution. In such cases, patients should be under close medical supervision .; Like levodopa, Tidomet Forte can cause mental disorders. The development of such reactions is associated with an increase in the content of dopamine in the brain during the use of levodopa. All patients taking the drug should be supervised in connection with the possibility of developing a depressive state with suicidal tendencies. Patients who have had psychosis, require a careful approach in the selection of therapy .; Patients who have suffered a myocardial infarction with atrial, nodular and ventricular arrhythmias, need a thorough preliminary examination. In such patients, cardiac activity should be monitored, with particular care when prescribing the first dose and during the dose selection period .; Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (about 2-6 times higher) of developing melanoma than the general population. Whether the observed increase in the risk of melanoma is associated with Parkinson's disease or other factors, such as medication for the treatment of Parkinson's disease, is unclear. Therefore, patients and physicians who frequently and regularly use the drug Tidomet Forte according to the required indications are advised to monitor the development of melanoma. Ideally, periodic skin examinations should be performed by qualified specialists (for example, dermatologists) .; Laboratory indicators: usually the level of creatinine and urea is lower than when using levodopa.Transient changes include an increase in plasma urea concentration, ALT, ACT, lactate dehydrogenase (LDH), bilirubin. When using the drug Tidomet Forte can be false positive result of the determination of ketones in the urine with the help of a litmus test; This reaction does not change when boiling urine. When determining glucose in the urine using a method based on the enzymatic reaction of glucose oxide, there may be a false negative result .; With prolonged treatment, it is necessary to periodically monitor the function of the liver, kidney, hematopoietic system and cardiovascular system, and the patient’s mental status must be monitored; In case of general anesthesia during surgical operations, Tidomet Forte is prescribed without reducing the dose, if the patient is able to take drugs and liquid inside. When using halothane and cyclopropane, the prescription of the drug is stopped at least 8 hours before the operation. The treatment is continued after the operation in the same dose .; Patients with open-angle glaucoma should be prescribed Tidomet Forte with caution. During treatment, it is necessary to regularly monitor intraocular pressure .; Influence on ability to drive motor transport and control mechanisms; Use of the drug can cause drowsiness and in rare cases, sudden sleep. Patients should be informed about this and the need to exercise caution when driving or driving machinery .; When prescribing Tidomet Forte, it is recommended to refrain from driving a car and controlling mechanisms that require increased attention and speed of psychomotor reactions.