Composition, form of production and packaging
Tablets are white or grayish-white, round, flat, chamfered, engraved "DOPEGYT" on one side, without or almost odorless.
1 tab.
methyldopa sesquihydrate 282 mg,
which corresponds to the content of methyldopa 250 mg
Excipients: ethyl cellulose - 8.8 mg, magnesium stearate - 1 mg, corn starch - 45.7 mg, stearic acid - 3 mg, sodium carboxymethyl starch - 3.5 mg, talc - 6 mg.
50 pcs. - bottles of brown glass with PE cover, with the control of the first opening and a shock absorber-accordion (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
Antihypertensive drug of central action. Metabolized with the formation of alpha-methylnoradrenaline, which has an antihypertensive effect through several mechanisms:
- reduction of sympathetic tone by stimulation of central inhibitory presynaptic ones? 2- receptors;
- Substitution of endogenous dopamine on dopaminergic nerve endings (as a false neurotransmitter);
- decrease in plasma renin activity and a decrease in OPSS;
- suppression of the synthesis of noradrenaline, a decrease in the concentration of dopamine, serotonin, noradrenaline and epinephrine in tissues due to inhibition of the activity of the enzyme dopa decarboxylase.
Methyldopa has no direct effect on heart function, does not reduce cardiac output, does not cause reflex tachycardia, and also does not reduce the glomerular filtration rate, renal blood flow, the filtered fraction. In some cases, the heart rate decreases. Effectively reduces blood pressure in both a prone position and a standing position.Rarely causes postural hypotension.
After taking a single oral dose, the maximum effect develops within 4-6 hours and lasts approximately 12-24 hours. With repeated use of the drug, the maximum decrease in blood pressure is achieved on day 2-3. After discontinuation of therapy, the blood pressure level returns to the initial values ​​within 1-2 days.
PHARMACOKINETICS
Suction
Absorption of methyldopa from the gastrointestinal tract is approximately 50%. After oral administration, the bioavailability of methyldopa is about 25%. C max in blood plasma is achieved in 2-3 hours.
Distribution
Binding to plasma proteins is less than 20%. Methyldopa penetrates the placental barrier and is excreted in breast milk.
Metabolism
Metabolism of methyldopa occurs intensively. Methyldopa is metabolized predominantly in the liver. Active metabolite of methyldopa - alpha-methylnoradrenaline, is formed in adrenergic neurons of the central nervous system. There are also some other methyldopa derivatives that are excreted from the body by the kidneys.
Excretion
Approximately two-thirds of the absorbed methyldopa is excreted from the body by the kidneys in unchanged form, as well as in the form of sulfate compounds. The rest of the drug is excreted through the intestine (also in the unmodified state). The excretion of methyldopa has a two-phase character. With preserved kidney function, T 1/2 of the drug is 1.8 В± 0.2 h. The active substance is completely eliminated from the body within 36 hours. Methyldopa is removed from the body by dialysis. A six-hour hemodialysis session results in the excretion of approximately 60% of the absorbed dose, whereas as a result of 20-30-hour peritoneal dialysis, approximately 22-39% of the drug is removed.
Pharmacokinetics in special clinical cases
When the function of the nights is disturbed, excretion of methyldopa slows in proportion to the severity of renal failure. In severe renal failure (without hemodialysis), T 1/2 of the drug increases approximately 10-fold.
INDICATIONS
- arterial hypertension.
DOSING MODE
Tablets are taken orally before or after meals. The dosage regimen is set individually.
Adult patients
The recommended initial dose of Dopegit В® in the first 2 days of therapy is 250 mg 2-3 times / day. Then the dose can be gradually increased or decreased (depending on the degree of BP reduction). The duration of intervals between increasing and decreasing the dose of Dopegit В® should be at least 2 days. Since 2-3 days after the start of therapy, as well as with a subsequent increase in the dose, there may be an adverse sedative effect of the drug, it is recommended first to increase the evening dose of the drug.
The standard maintenance dose of Dopegit В® is 0.5-2 g / day. This dose is divided into 2-4 admission. The maximum daily dose of the drug should not exceed 3 g. In cases when against the background of taking the drug at a dose of 2 g / day, there is not enough effective reduction in blood pressure, it is recommended to combine Dopegit В® with other antihypertensive drugs. After 2-3 months of therapy, tolerance to methyldopa may develop. Effective reduction in blood pressure can be achieved by increasing the dose of the drug or concomitant use of diuretics. After 48 hours after discontinuation of therapy with Dopyrite В® , the blood pressure usually returns to the baseline level. "Ricochet effect" is not observed.
Dopegit В® can be administered to patients who are already receiving therapy with other antihypertensive drugs, subject to gradual withdrawal of these drugs. In such cases, the initial dose of Dopegit В® should not exceed 500 mg / day. The dose is increased as needed, with intervals of at least 2 days.
When using Dopegit В® in addition to the previously prescribed antihypertensive therapy, in order to guarantee a smooth transition, it may be necessary to adjust the doses of antihypertensive drugs.
Elderly patients
Elderly patients are prescribed a minimum initial dose, which should not exceed 250 mg / day. If necessary, the dose can be gradually increased. The duration of intervals between increasing the dose of the drug is at least 2 days. The maximum daily dose of Dopegit В® should not exceed 2 g.
Fainting is common in elderly patients. This may be due to increased susceptibility to the drug and pronounced atherosclerotic vascular lesions. The development of fainting can be avoided by reducing the dose of Dopegit В® .
Children over 3 years old
For children, the initial dose of the drug is 10 mg / kg body weight / day. The daily dose is divided into 2-4 admission. If necessary, the dose can be gradually increased until the desired effect is achieved. Between the increase in the dose of the drug should be observed interval of at least 2 days. The maximum daily dose of Dopegit В® is 65 mg / kg body weight / day, but not more than 3 g / day.
Renal impairment
Methyldopa is excreted mainly by the kidneys, so when treating patients with impaired renal function, the dose of Dopegit В® should be reduced. For mild renal failure (glomerular filtration rate is 60-89 ml / min / 1.73 m 2 ), the interval between doses of the drug should be increased to 8 hours, with renal failure of moderate severity (glomerular filtration rate is 30-59 ml / min / 1.73 m 2 ) - up to 8-12 hours, and with severe renal failure (glomerular filtration rate - <30 ml / min / 1.73 m 2 ) - up to 12-24 hours.
Methyldopa is removed from the body during dialysis, therefore it is recommended to use an additional dose of 250 mg to prevent the increase in blood pressure after a hemodialysis session.
SIDE EFFECT
At the beginning of therapy with Dopegit В® , as well as increasing the dose of the drug, transient sedation, headache, general weakness and increased fatigue can be observed.
Classification of adverse reactions depending on frequency: very often (> 1/10), often (> 1/100 to <1/10), infrequently (from> 1/1000 to <1/100), rarely (> 1/10 000 to <1/1000), very rarely (<1/10 000), isolated cases.
In each of these categories, undesirable effects are presented in descending order of severity.
From the cardiovascular system: very rarely - the progression of angina pectoris, myocarditis, pericarditis; individual cases - congestive heart failure, prolonged hypersensitivity of the carotid sinus, orthostatic hypotension (recommended dose reduction), peripheral edema, weight gain, sinus bradycardia.
Peripheral edema and weight gain usually regress with diuretic therapy. If swelling builds up or signs of heart failure appear, the drug should be discontinued.
From the side of the central nervous system: very rarely - parkinsonism; individual cases - peripheral paralysis of the facial nerve (Bell's paralysis), loss of intelligence, involuntary choreoathetotic motor activity, symptoms of cerebral circulatory insufficiency (possibly as a consequence of hypotension), mental disorders, (including nightmarish dreams, usually reversible mild psychosis and depression), headache , sedation (usually transient), general weakness or increased fatigue, dizziness, paresthesia, decreased libido.
On the part of the respiratory system: individual cases - nasal congestion.
From the side of the digestive system: very rarely - pancreatitis; individual cases - colitis, vomiting, diarrhea, inflammation of the salivary glands, pain or dark staining of the tongue, nausea, constipation, bloating, flatulence, dry mouth, hepatitis, necrotic hepatitis; cholestasis, jaundice.
On the part of the skin: individual cases - toxic epidermal necrolysis, eczema or a rash, resembling lichen.
From the musculoskeletal system: individual cases - mild pain in the joints with or without edema, myalgia.
On the part of the endocrine system: isolated cases - hyperprolactinaemia, gynecomastia, galactorrhea, amenorrhea.
From the immune system: individual cases - vasculitis, lupus syndrome, drug fever, eosinophilia.
Laboratory indicators: very often - a positive test of Coombs; rarely - hemolytic anemia, leukopenia, granulocytopenia, thrombocytopenia; individual cases - depression of bone marrow function, positive results of tests for antinuclear antibodies, LE cells and rheumatoid factor, increased activity of hepatic transaminases, increased urea concentration in the blood.
Other: individual cases - impotence, ejaculation disorders.
CONTRAINDICATIONS
- Acute hepatitis, cirrhosis of the liver;
- liver disease in the history (on the background of methyldopy);
- concomitant therapy with MAO inhibitors;
- Depression;
- hemolytic anemia;
acute myocardial infarction;
- pheochromocytoma;
- Children's age up to 3 years (for this dosage form);
- Hypersensitivity to the drug.
With caution should prescribe the drug for kidney failure (requires dose adjustment), diencephalic syndrome, elderly patients and children over the age of 3 years.
PREGNANCY AND LACTATION
According to the results of clinical studies after the application of methyldopa in the II and III trimesters of pregnancy, no signs of damage to the fetus or newborn have been revealed. Since adequate and strictly controlled studies in the III trimester of pregnancy have not been conducted, the drug is recommended only after a careful comparison of the expected benefit of therapy for the mother and the potential risk to the fetus.
The study of children born to mothers who took methyldopa after the 26th week of pregnancy did not reveal any undesirable effects of the drug. In pregnant women who took the drug in the third trimester, the condition of the fetus was better than in women who do not take the drug.
Methyldopa is excreted in breast milk, so it is recommended to prescribe the drug during lactation only after careful comparison of the expected benefit for the mother and the potential risk to the child.
APPLICATION FOR FUNCTIONS OF THE LIVER
Methyldopa is excreted mainly by the kidneys, so when treating patients with impaired renal function, the dose of Dopegit В® should be reduced. For mild renal failure (glomerular filtration rate is 60-89 ml / min / 1.73 m 2 ), the interval between doses of the drug should be increased to 8 hours, with renal failure of moderate severity (glomerular filtration rate is 30-59 ml / min / 1.73 m 2 ) - up to 8-12 hours, and with severe renal failure (glomerular filtration rate - <30 ml / min / 1.73 m 2 ) - up to 12-24 hours.
Methyldopa is removed from the body during dialysis, therefore it is recommended to use an additional dose of 250 mg to prevent the increase in blood pressure after a hemodialysis session.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in acute hepatitis, cirrhosis, patients who have a history of liver disease, developed against the background of methyldopa.
Patients with a history of liver disease or a history of liver function should be given this medication with extreme caution.
APPLICATION FOR CHILDREN
Children over 3 years old
For children, the initial dose of the drug is 10 mg / kg body weight / day. The daily dose is divided into 2-4 admission. If necessary, the dose can be gradually increased until the desired effect is achieved. Between the increase in the dose of the drug should be observed interval of at least 2 days. The maximum daily dose of Dopegit В® is 65 mg / kg body weight / day, but not more than 3 g / day.
Contraindicated in children under 3 years.
APPLICATION IN ELDERLY PATIENTS
Elderly patients are prescribed a minimum initial dose, which should not exceed 250 mg / day. If necessary, the dose can be gradually increased. The duration of intervals between increasing the dose of the drug is at least 2 days. The maximum daily dose of Dopegit В® should not exceed 2 g.
Fainting is common in elderly patients. This may be due to increased susceptibility to the drug and pronounced atherosclerotic vascular lesions. The development of fainting can be avoided by reducing the dose of Dopegit В® .
SPECIAL INSTRUCTIONS
In rare cases, patients taking methyldopa developed hemolytic anemia. When signs of anemia appear, it is necessary to determine the concentration of hemoglobin and hematocrit. If anemia is confirmed, the degree of hemolysis should be further assessed. If hemolytic anemia develops, Dopegit В® should be discontinued. After discontinuation of therapy (with or without corticosteroids), it is usually possible to quickly achieve remission. Nevertheless, in rare cases, lethal outcomes were observed. Dopegit В® is contraindicated in patients with hemolytic anemia, which has developed against the background of therapy with this drug.
In some patients who have been taking Dopegit В® for a long time, a positive Coombs test is determined. According to reports of various researchers, the prevalence of this reaction varies from 10 to 20%. A positive Coombs test is rarely seen during the first 6 months of therapy. If this phenomenon does not develop during the first 12 months of therapy, then it is unlikely to reveal it in the future. The prevalence of a positive Coombs test is dose-dependent. Most rarely this phenomenon is observed in patients taking the drug at a dose of 1000 mg / day or less. The Coombs test, positive for methyldopa, becomes negative after a few weeks or months after discontinuation of therapy with the drug. Before starting treatment, and also at the 6th and 12th month of therapy, it is recommended to perform a general blood test and a direct Coombs test.
The identification of a positive Coombs test in the past or against the background of the therapy itself is not a contraindication to taking Dopegit В® . In cases where the positive direct Coombs test is detected against the background of the drug, it is necessary to exclude the presence of hemolytic anemia in the patient and to determine the clinical significance of this phenomenon.
Information on previous positive results from the Coombs test helps in assessing blood for cross-compatibility before transfusion. If, in the treatment of a patient taking Dopegit В® , there is a need for transfusion, then before the blood transfusion it is necessary to perform both a direct and an indirect Coombs test. In the absence of hemolytic anemia, only the direct Coombs test is usually positive. Positive direct Coombs test does not affect the determination of the blood group and the result of the sample for cross-compatibility. If the indirect Coombs test is also positive, then there may be difficulties in assessing cross-compatibility. In such cases, a consultation of a hematologist or transfusiologist is necessary.
In rare cases, against the background of methyldopa therapy, reversible leukopenia and granulocytopenia were observed. After cessation of therapy, the amount of granulocytes returned to normal. In addition, patients who took methyldopa had rare cases of reversible thrombocytopenia.
Some patients experienced fever during the first three weeks of therapy with the drug, which was sometimes accompanied by eosinophilia or increased hepatic transaminase activity. In addition, the reception of methyldopa may be accompanied by the development of jaundice. Jaundice usually appears during the first 2-3 months of therapy. In some cases, against a background of jaundice, cholestasis was confirmed. Very rarely, patients developed fatal necrotizing hepatitis. A liver biopsy performed in several patients with impaired function of this organ showed microscopic focal necrosis, characteristic of drug hypersensitivity. Before taking the drug dopegit В® , 6 and 12 weeks of treatment, as well as at any time when a unexplained fever recommended to determine the activity of hepatic transaminases and CBC with leukocyte formula.
When fever, jaundice or increases in liver transaminases, the drug dopegit В® must be immediately stopped. If the appearance of symptoms associated with hypersensitivity to methyldopa, after discontinuation fever disappears, and liver function tests return to normal values. Such patients are not recommended to renew the drug. Patients with a history of liver disease therapy with dopegit В® should be carried out with extreme caution.
Patients receiving dopegit В® , may require dose reduction anesthetics. With the development of hypotension during general anesthesia is recommended vasopressor therapy. Adrenergic receptors do not lose their sensitivity to the background of methyldopa therapy.
Some patients taking methyldopa, there are peripheral edema, and increased body weight. These side effects are easily eliminated by diuretics. With an increase in swelling and the appearance of symptoms of heart failure therapy with dopegit В® must stop.
Since methyldopa removed from the body by dialysis, blood pressure level increase may occur after the session ends.
Patients with bilateral lesions of cerebral vessels (cerebrovascular disease) receiving methyldopa may be accompanied by involuntary movements horeoatetoticheskimi. In these cases, drug therapy should be discontinued.
The drug dopegit В® must be applied with great caution in treating patients with hepatic porphyria, and their close relatives.
Drug therapy dopegit В® can affect the results of measurement of uric acid concentration (using phosphotungstic reagent), creatinine (using the alkaline picrate) and AST (colorimetric method) in serum. The effect of methyldopa therapy on spectrophotometric analysis of the concentration of AST have been reported.
On the background of methyldopa therapy can be obtained false positive results of the determination of catecholamines in urine fluorescence method, which complicates the diagnosis of pheochromocytoma. At the same time, methyldopa has no effect on the assessment vanillylmandelic acid concentration in urine.
In rare cases, the air urine of patients taking methyldopa, may darken. This effect is associated with the decomposition of methyldopa and its metabolites. During the reception of the drug dopegit В® should not drink alcoholic beverages.
Impact on the ability to drive vehicles and manage mechanisms
Drug therapy dopegit В® may be accompanied by a sedative effects which are usually transient and developed at the beginning of treatment, or at higher dosage. With the development of these effects, patients should not undertake activities that require attention, such as driving vehicles or machinery.
OVERDOSE
Symptoms: marked reduction of blood pressure, dizziness, severe drowsiness, weakness, bradycardia, lethargy, tremors, intestinal atony, constipation, bloating, flatulence, diarrhea, nausea, vomiting.
Treatment: gastric lavage, vomiting stimulation may reduce the amount of the drug has grown deep. Necessary to monitor heart rate, bcc, water and electrolyte balance, bowel and kidney function as well as the brain. If necessary, can be administered sympathomimetics (e.g., epinephrine). There is no specific antidote.
DRUG INTERACTION
Dopegit В® can not be used simultaneously with MAO inhibitors.
The simultaneous use of the following drugs requires special care.
Drugs that reduce the antihypertensive effect dopegit preparation В® : sympathomimetics (increase pressor effect), tricyclic antidepressants, phenothiazines (at the same time they can have an additive antihypertensive effect), iron preparations for oral administration (they may reduce the bioavailability of methyldopa), NSAID, estrogen preparations .
Formulations reinforcing antihypertensive effect dopegit preparation В®: Other antihypertensives, beta blockers (increased antihypertensive effect), levodopa + carbidopa (development of orthostatic hypotension, in this case, after the patients taking the drugs must be in a horizontal position within 1-2 h), general anesthetics, antianxiety drugs (tranquilizers).
Methyldopa and the following drugs may change Effects of each other: Li (danger amplification lithium toxicity), levodopa (reduction antiparkinson effect and increased unwanted actions on the CNS), ethanol and other drugs, CNS depressants (increased depression), anticoagulants (increased anticoagulant effect, bleeding risk), bromocriptine (possibly adverse effect on prolactin), haloperidol (possibly cognitive impairment - disorientation and confused state of mind).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of reach of children at a temperature of from 15 В° to 25 В° C. Shelf life - 5 years.
