Tidomette forte - instructions for use, dose, side effects, contraindications

Composition:Active substances: levodopa 250 mg, carbidopa 25 mg; Excipients: povidone K-30 9 mg, talc 6 mg, magnesium stearate 5.5 mg, starch (dry) 12 mg, silicon dioxide colloid 5 mg, cellulose microcrystalline 85.5 mg.

Description:Kaya tablet from white to almost white with a risk on one side of the tablet.

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

ATX: & nbsp

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

Pharmacodynamics:Levodopa is an amino acid derived from L-tyrosine. Dopamine is formed directly from levodopa with the participation of the cytoplasmic enzyme-decarboxylase of aromatic L-amino acids.The end result of dopamine is the inhibition of neuronal activity in the striatum of the brain. Levodopa rapidly decarboxylated in peripheral tissues under the influence of aromatic L-amino acids, dependent on pyridoxine decarboxylase, turning into dopamine, which, however, does not penetrate the blood-brain barrier. Carbidopa inhibits the decarboxylation of levodopa in peripheral tissues, without penetrating the blood-brain barrier and does not affect the conversion of levodopa to dopamine in the central nervous system. Thus, the combination of carbidopa and levodopa increases the amount of levodopa that enters the brain. When combined ingestion of carbidopa doubles the bioavailability of levodopa. The introduction of carbidopa never leads to complete inhibition of decarboxylase of aromatic L-amino acids.

Pharmacokinetics:

a. 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.Barrier on the way of absorption of levodopa is the presence of decarboxylase of aromatic L-amino acids in the intestinal wall. From the stomach levodopa is absorbed in a limited amount. The rate of gastric emptying plays a key role in the absorption of levodopa. Factors slowing the emptying of the stomach (food, m-holinoblokiruyuschie means), delay passage of levodopa into the duodenum and slow its absorption. The maximum concentration of levodopa in the blood is noted 1-2 hours after the administration.

Distribution: The volume of distribution of levodopa is 0.9-1.6 l / kg. While maintaining the activity of decarboxylase aromatic L-amino acids, the total clearance of levodopa in blood plasma is 0.5 l / kg / h. Levodopa penetrates the blood-brain barrier by facilitated diffusion. The endothelium of the capillaries of the brain also contains aromatic L-amino acid decarboxylases as the second potential barrier to the passage of levodopa into the brain, however, in these capillaries an insignificant part of the injected dose of levodopa is decarboxylated. Metabolism: Approximately 70-75% of the administered levodopa is metabolized in the intestinal wall (the "first pass" effect). Liver in the metabolism of the first passage of participation is almost not accepted.With increasing dose, the amount of levodopa, which undergoes decarboxylation in the intestine, decreases. Levodopa does not bind to blood plasma proteins. Decarboxylation of levodopa with decarboxylase of aromatic L-amino acids is the main way to form dopamine from levodopa. A large amount of this enzyme is found in the intestines, liver and kidneys. Methoxylation of levodopa under the influence of catechol-O-methyltransferase to form 3-O-methyldopa is the second way of metabolizing levodopa. With long-term treatment, this metabolite can accumulate. Transamination is an additional way of metabolizing levodopa. The final product of this route is vanilly pyruvate, vanilla acetate and 2,4,5-trihydroxyphenylacetic acid. All metabolic pathways, with the exception of transamination, are irreversible.

Excretion: In combination with carbidopa, the half-life of levodopa increases to 3 hours. Up to 69% of levodopa can be found in the urine of a person in the form of dopamine and its metabolites - vinilinmindalic acid, noradrenaline, homovanilic acid, dihydrophenylacetic acid.

b. Carbidopa

In recommended doses, carbidopa does not penetrate the blood-brain barrier. The maximum concentration in the blood plasma is achieved in 2-4 hours. Approximately 50% of carbidopa is excreted in urine and feces. 35% of carbidopa, excreted by the kidneys, is excreted unchanged.

Indications:Parkinson's disease; Parkinson's syndrome (postencephalitic parkinsonism, parkinsonism due to intoxication with carbon monoxide and (or) manganese).

Contraindications:Hypersensitivity to any component of the drug-closure glaucoma, severe neurosis or psychosis, melanoma or suspected it, skin disease of unknown etiology, Huntington's disease, essential tremor, concomitant use of non-selective inhibitors of monoamine oxidase (MAO). It should not be used for the treatment of secondary parkinsonism caused by the use of antipsychotics (neuroleptics). It is not recommended for use in children under the age of 18 due to insufficient data on efficacy and safety.

Carefully:The drug is administered with caution in case of erosive and ulcerative lesions of the stomach and / or duodenum,epileptic seizures in the anamnesis, myocardial infarction with heart rhythm disorders in the anamnesis, heart failure, endocrine system diseases (including diabetes mellitus), bronchial asthma, mental disorders, as well as severe violations of the liver and kidneys.

Pregnancy and lactation:

The effect of the drug on the course of pregnancy in women is unknown. In experimental studies, it was found that the combination of levodopa and carbidopa causes visceral and skeletal changes in animals. Therefore, the use of the drug is possible only if the expected benefit of therapy for the mother exceeds the potential risk to the fetus.

It is not known whether they are excreted in breast milk levodopa and carbidopa. There is one report on 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 the therapy for the mother, if the drug is needed during lactation, it should either stop breastfeeding or cancel the drug.

Dosing and Administration:

Inside, with a small amount of food or after a meal, washing down with water and not chewing. Since there is competition between aromatic amino acids and levodopa during absorption, during the use of the drug, the consumption of a large number of proteins should be avoided.

The average daily dose of carbidopa, necessary to suppress peripheral conversion of levodopa, is 70-100 mg. Excess of 200 mg of carbidopa does not entail a further increase in the therapeutic effect. The daily dose of levodopa should not exceed 2000 mg.

The initial dose - 1/2 tablets 2 times a day, if necessary, you can increase the number of tablets per day. As a rule, at the beginning of replacement therapy, the daily dose should not exceed 3 tablets per day (1 tablet 3 times a day). The 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 can be increased with monotherapy, but should not exceed 8 tablets (1 tablet 8 times a day). Use in quantities of more than 6 tablets per day should be done with great care.

Tidometh Forte when replacing levodopa

Pig levodopa is discontinued 12 hours before treatment with Tidometh Forte, and in the case of prolonged forms of levocarbidopa - for 24 hours. The dose of Tidometh Forte in this case should not exceed 20% of the previous dose of levodopa. The maintenance dose is 3-6 tablets per day for most patients.

Side effects:

Most often - dyskinesia, including involuntary movements (including choreiform, dystonic), and nausea.

Early signs on the basis of which a decision can be made to abolish the drug are muscle twitchings and blepharospasm.

Other side effects:

From the nervous system: psychotic reactions, including delirium, hallucinations and paranoid thinking, malignant neuroleptic syndrome (see "Special instructions"), episodes of bradykinesia ("on-off" syndrome), agitation, paresthesia, dizziness, drowsiness, sleep disturbance, including nightmares, insomnia ; confusion, headache, depression (including with suicidal intentions), dementia, pathological predilections, increased libido.It was reported about the development of seizures, but the cause-and-effect relationship with taking the drug is not established.

From the digestive system: vomiting, anorexia, diarrhea, constipation, dyspepsia, dryness of the oral mucosa, taste change, saliva darkening, gastrointestinal bleeding, duodenal ulcer. From the cardiovascular system: arrhythmia and / or palpitations, orthostatic reactions, including a decrease or increase in blood pressure, blood pressure; phlebitis.

On the part of the hematopoiesis system: leukopenia, thrombocytopenia, anemia (including hemolytic), agranulocytosis.

Allergic reactions: angioedema, urticaria, pruritus, hemorrhagic vasculitis (purpura Shenlaine-Henoch), bullous eruptions (including reactions similar to pemphigus).

From the respiratory system: shortness of breath, upper respiratory tract infection. From the skin: skin rash, excessive sweating, darkening sweat, alopecia.

From the urinary system: urinary tract infections, frequent urination, darkening of urine.

Change in laboratory indicators: decrease in hemoglobin and hematocrit, increased activity of alanine aminotransferase (AJIT), aspartate aminotransferase (ACT), lactate dehydrogenase, alkaline phosphatase, hyperbilirubinemia, increased urea nitrogen, positive Coombs test, hyperglycemia, leukocyturia, bacteriuria and hematuria.

Other: pain in the chest, asthenia.

Below are listed other adverse reactions that were observed with the use of levodopa alone, which means that they can be observed with Tidomette Forte:

From the cardiovascular system: myocardial infarction.

From the digestive system: gastrointestinal pain, dysphagia, salivation, flatulence, bruxism, a burning sensation of the tongue, heartburn, hiccups.

From the side of metabolism: edema, decreased or increased body weight.

From the nervous system: ataxia, extrapyramidal disorders, falls, anxiety, gait disturbance, nervousness, decreased thinking, memory loss, disorientation, euphoria, blepharospasm, trisus, tremor aggravation, stupor, muscle twitching, activation of Horner's latent syndrome, peripheral neuropathy.

From the respiratory system: pain in the throat, cough.

From the skin: Malignant melanoma, "hot flashes" of blood.

From the sense organs: oculogic crisis, diplopia, impaired vision, mydriasis. From the genitourinary system: urinary retention, urinary incontinence, priapism.

Other: abdominal pain, fatigue, weakness, pain in the lower extremities, dyspnea, malaise, hoarseness of voice, agitation.

From the laboratory indicators: leukopenia, hypokalemia, hypercreatininaemia and hyperuricemia, proteinuria and glucosuria.

Overdose:Treatment: gastric lavage, close observation and ECG monitoring for the timely detection of arrhythmia; if necessary, antiarrhythmic therapy.

Interaction:

- simultaneous use with antihypertensive drugs requires special attention in connection with the danger of postural hypotension;

- while simultaneous application of levodopa with monoamine oxidase (MAO) inhibitors (with the exception of MAO-B inhibitors), circulatory disorders are possible (administration of MAO inhibitors should be discontinued in 2 weeks). This is due to the accumulation under the influence of levodopa dopamine and norepinephrine,metabolism of which is inhibited by MAO inhibitors, and a high probability of agitation, increased blood pressure (BP), tachycardia, facial flushing and dizziness;

- when combined with tricyclic antidepressants, arterial hypertension and dyskinesia may occur, as well as a decrease in the bioavailability of levodopa;

- when combined with D2-dopamine receptor agonists (phenothiazine, butyrophenone derivatives), as well as with isoniazid, the therapeutic effect of levodopa may be reduced;

- can increase the effect of adrenomimetics, in connection with which it is recommended to reduce their dose. With the simultaneous use of levodopa with β-adrenomimetics, the means for inhalation anesthesia may increase the risk of heart rhythm disturbances;

- when using amantadine with levodopa, there is a potentiating effect;

- methyldopa and levodopa can potentiate side effects of each other;

- pyridoxine is a cofactor of the decarboxylase of aromatic L-amino acids, the enzyme responsible for the peripheral decarboxylation of levodopa and the formation of dopamine.When he is prescribed to patients receiving levodopa (without inhibitors of decarboxylase of aromatic L-amino acids), there is an increase in peripheral metabolism of levodopa and a smaller amount of it penetrates the blood-brain barrier. In this way, pyridoxine reduces the therapeutic effect of levodopa, unless additional inhibitors of peripheral decarboxylase of aromatic L-amino acids are prescribed;

- with the additional administration 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, thioxanthene derivatives, papaverine, reserpine, m-cholinergic blockers, a decrease in the antiparkinsonian effect is possible;

- while simultaneous use with lithium (Li +) drugs increases the risk of dyskinesias and hallucinations;

- iron salts can reduce the bioavailability of levodopa and carbidopa; the clinical significance of such an interaction is unknown;

- although metoclopramide increases the bioavailability of levodopa, accelerating the emptying of the stomach, nevertheless,it can adversely affect the control of the disease due to its antagonism with dopamine receptors.

Special instructions:It should not be used in cases of secondary parkinsonism (Parkinson's syndrome) caused by the use of antipsychotics (neuroleptics). Discontinue treatment should be gradual, because with a sudden discontinuation of the drug may develop a symptom complex that resembles a malignant neuroleptic syndrome (muscle rigidity, fever, increased activity of creatine phosphokinase (CK) in the blood serum). It is necessary to monitor patients who suddenly needed to lower the dose of the drug or interrupt its reception. Absorption of levodopa in elderly patients is higher than in young patients. These data confirm the information on the decrease in the activity of aromatic L-amino acid decarboxylase in tissues with age, as well as with the long-term use of levodopa. With erosive and ulcerative lesions of the stomach and / or duodenum, epileptic seizures in the anamnesis, myocardial infarction with a history of rhythm disturbances, heart failure, diabetes, bronchial asthma,diseases of the endocrine system, mental disorders, as well as severe violations of the liver or kidneys should be taken with caution. In such cases, patients should be under close supervision of the doctor. As well as levodopa, Tidometh Forte can cause mental disorders. The development of such reactions is associated with an increase in dopamine in the brain with levodopa. All patients taking the drug should be monitored in connection with the possibility of developing a depressive state with suicidal tendencies. Patients in whom psychoses were observed require a cautious approach in the selection of therapy.

Patients who underwent myocardial infarction, who had atrial, nodal and ventricular arrhythmias, needed a thorough preliminary examination. Such patients need to monitor cardiac activity, with particular care - with the appointment of the first dose and during the selection of doses. Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (approximately 2-6 fold higher) of developing melanoma than the general population.It connected whether the observed increased risk of melanoma with Parkinson's disease or other factors, such as taking medicines to treat Parkinson's disease, is unclear. Therefore, patients and doctors, who often and on a regular basis use the drug Tidomet Forte for the necessary indications, it is recommended to monitor the development of melanoma. Ideally, periodic examinations of the skin 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 increased urea concentration in the blood plasma, ALT, ACT, lactate dehydrogenase (LDH), bilirubin. When using Tidometh Forte, there may be a false positive result of determining ketones in the urine with a litmus test; this reaction does not change when urine is boiled. When determining glucose in urine using a method based on the enzymatic reaction of glucose oxidase, there may be a false-negative result. With prolonged treatment, periodic monitoring of liver function, kidney function, hematopoiesis and cardiovascular system is necessary, as well as monitoring of the patient's mental status.

With general anesthesia during surgery, Tidometh Forte is prescribed without lowering the dose, if the patient is able to take drugs and liquid inside. When using halothane and cyclopropane, the drug is discontinued at least 8 hours before the operation. Treatment continues after the operation in the same dose. Patients with open-angle glaucoma should be appointed Tidometh Forte with caution. During treatment, it is necessary to regularly monitor the intraocular pressure.

The use of the drug may cause drowsiness and, in rare cases, sudden falling asleep. Patients should be informed about this and the need to exercise caution when driving or operating machinery.

Effect on the ability to drive transp. cf. and fur:When appointing Tidometh Forte, it is recommended to refrain from driving a car and controlling mechanisms that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Pills.

Packaging:

10 tablets per strip of aluminum foil. For 5 or 10 strips together with instructions for use in a cardboard pack.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012502 / 01

Date of registration:12.01.2012

The owner of the registration certificate:Torrent Pharmaceuticals Co., Ltd.Torrent Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

TORRENT PHARMACEUTICALS, Ltd. India

Representation: & nbspTORRENT PHARMACEUTICALS LTD. TORRENT PHARMACEUTICALS LTD. India

Information update date: & nbsp23.08.2015

Illustrated instructions

Instructions

Tidomet forte (Tidomet forte)