Directions for use and doses
Inside. Therapy with Dopegit® requires individual dosage selection. The drug can be taken both before and after meals.
Adult patients. The recommended initial dose of Dopegit® in the first 2 days of therapy is 250 mg 2-3 times a day. Then the dose can be gradually increased or decreased (depending on the degree of blood pressure reduction). The duration of the intervals between increasing and decreasing the dose of Dopegit® should be at least 2 days. Since side sedative effects of the drug may be observed within 2-3 days after the start of therapy, as well as with subsequent increases in the dose, it is recommended to first increase the evening dose of the drug.
The standard maintenance dose of Dopegit® is 500–2000 mg/day. This dose is divided into 2–4 doses. The maximum daily dose of the drug should not exceed 3000 mg. In cases where an insufficiently effective reduction in blood pressure levels is observed while taking the drug at a dose of 2000 mg/day, it is recommended to combine Dopegit® with other antihypertensive drugs.
After 2–3 months of therapy, tolerance to methyldopa may develop. Effective reduction of blood pressure can be achieved by increasing the dose of the drug or concomitant use of diuretics.
48 hours after stopping therapy with Dopegit®BP, blood pressure usually returns to its original level. The rebound effect is not observed.
Dopegit® can be prescribed to patients who are already receiving therapy with other antihypertensive drugs, provided that these drugs are gradually withdrawn. In such cases, the initial dose of Dopegit® should not exceed 500 mg/day. The dose is increased as needed, at intervals of at least 2 days.
When using Dopegit® in addition to previously prescribed antihypertensive therapy, dose adjustment of antihypertensive drugs may be required to ensure a smooth transition.
Elderly patients. For elderly patients, the drug is prescribed in a minimum initial dose, which should not exceed 250 mg/day. If necessary, the dose can be gradually increased. The duration of the intervals between increasing the dose of the drug is at least 2 days. The maximum daily dose of Dopegit® should not exceed 2000 mg.
Older patients are more likely to experience fainting. This may be due to increased susceptibility to the drug and severe atherosclerotic vascular damage. The development of fainting can be avoided by reducing the dose of Dopegit®.
Children over 3 years old. For children, the initial dose of the drug is 10 mg/kg/day. The daily dose is divided into 2–4 doses. If necessary, the dose can be gradually increased until the desired effect is achieved. An interval of at least 2 days must be maintained between increasing the dose of the drug. The maximum daily dose of Dopegit® is 65 mg/kg/day, but not more than 3 g/day.
Renal dysfunction. Methyldopa is excreted primarily by the kidneys, therefore, when treating patients with impaired renal function, the dose of Dopegit® must be reduced. For mild renal failure (glomerular filtration rate (GFR) 60–89 ml/min/1.73 m2), the interval between doses of the drug is recommended to be increased to 8 hours, for moderate renal failure - to 8–12 hours (GFR 30–59 ml /min/1.73 m2), and in severe renal failure - up to 12–24 hours (GFR <30 ml/min/1.73 m2).
Methyldopa is removed from the body during dialysis, so it is recommended to use an additional dose of 250 mg to prevent an increase in blood pressure after a hemodialysis session.
Dopegit 250 mg No. 50 tablet.
Instructions for medical use of the drug DOPEGITâ Trade name Dopegitâ International nonproprietary name Methyldopa Dosage form Tablets 250 mg Composition One tablet contains the active substance - methyldopa anhydrous 250 mg (equivalent to methyldopa sesquihydrate 282 mg), excipients: corn starch, ethylcellulose, talc, sodium starch glycolate (type A), stearic acid, magnesium stearate. Description White or grayish-white round flat tablets with a bevel, smooth on one side, engraved with DOPEGYT on the other side, odorless or almost odorless. Pharmacotherapeutic group Antihypertensive drugs. Central agonists. Methyldopa (levorotatory). ATC code C02A B01 Pharmacological properties Pharmacokinetics Absorption of methyldopa from the gastrointestinal tract is variable. After oral administration, bioavailability is 25%. Maximum plasma concentration is achieved after 2-3 hours. Binding to plasma proteins is less than 20%. The site of the main and intensive metabolism of methyldopa is the liver. The drug's active metabolite, alpha-methylnorepinephrine, originates from central adrenergic neurons. In addition, many other metabolites are known to be excreted in urine. Approximately 2/3 of methyldopa is excreted in the urine as methyldopa or sulfate conjugate, and the remaining amount is excreted unchanged in the feces. Removal is biphasic. With normal renal function, the half-life is 1.8 ± 0.2 hours. The active component of the drug is completely eliminated from the body within 36 hours. Methyldopa is eliminated during hemodialysis. Six-hour hemodialysis can remove 60% of the absorbed dose of methyldopa from the circulating blood, and peritoneal dialysis within 20-30 hours removes approximately 22-39%. Methyldopa crosses the placental barrier and is excreted into breast milk. The maximum reduction in blood pressure occurs 4 - 6 hours after taking one dose orally and lasts 12 - 24 hours. After repeated administration, the maximum hypotensive effect develops within 2 to 3 days. After discontinuation of the drug, blood pressure returns to its original level within 1 to 2 days. In renal failure, the elimination of methyldopa slows down in accordance with the degree of decline in renal function. In severe cases (without hemodialysis), the half-life of methyldopa is extended by 10 times. Pharmacodynamics The active substance of the drug, methyldopa, is a centrally acting antihypertensive agent. The mechanism of its action is currently still completely unknown. The active metabolite (α-methylnorepinephrine) formed in the central nervous system stimulates central inhibitory presynaptic α2-adrenoreceptors, reducing sympathetic tone; replaces endogenous dopamine in dopaminergic nerve endings as a false neurotransmitter; reduces plasma renin activity and reduces peripheral vascular resistance; inhibits the enzyme dopa decarboxylase, thereby reducing the synthesis of norepinephrine, dopamine, serotonin and the concentration of norepinephrine and adrenaline in tissues. Dopegit has no direct effect on cardiac function, does not reduce cardiac output, does not cause reflex tachycardia, and does not reduce glomerular filtration rate, renal blood flow, or filtered fraction. In some cases, the heart rate decreases. The drug reduces blood pressure when the patient is lying down or standing and only in rare cases causes orthostatic hypotension. Indications for use: arterial hypertension. Method of administration and dosage: Tablets for oral administration. The tablets can be taken before or after meals. The recommended starting dose is 250 mg 2-3 times a day for the first two days. The daily dose may then be increased or decreased, depending on the degree of blood pressure reduction, at two-day intervals. To reduce the severity of sedation, which is possible at the beginning of the course of treatment and when increasing the dose, first increase the evening dose. Maintenance dose - 500-2000 mg 2-4 times a day. If the drug is insufficiently effective at a dose of 2 g/day, it is recommended to use a combination with other antihypertensive drugs. After 1 to 3 months of treatment, tolerance may develop. Effective blood pressure control can be restored by adding a diuretic or increasing the dose of methyldopa. After discontinuation of Dopegyt, blood pressure returns to the initial level after 48 hours without the phenomenon of reverse effects. Dopegit can also be used in patients who are already taking other antihypertensive drugs, gradually withdrawing the previous drug. In such cases, the recommended starting dose is 500 mg per day. To achieve the desired therapeutic effect, the dose can be increased at intervals of at least two days. If Dopegit is used as an addition to existing antihypertensive therapy, it may be necessary to change the dose of the antihypertensive drug so that the transition to combination therapy occurs without complications. In elderly patients, the initial dose should be lower and not exceed 500 mg/day. If necessary, the dose can be gradually increased every 2 days to a maximum dose of 2 g/day, which cannot be exceeded. Syncope (loss of consciousness), which is more often observed in elderly patients, probably associated with the increased sensitivity of elderly patients and with a pronounced narrowing of the lumen of blood vessels, can be avoided by using lower doses. If renal function is impaired, reduced doses should be used. In case of mild renal failure (glomerular filtration rate GFR > 50 ml/min), an interval of 8 hours should be maintained between doses, in case of moderate renal failure (GFR = 10-50 ml/min) with an interval of 8-12 hours, and in case of severe renal failure (GFR < 10 ml/min) 12-24 hours. Since methyldopa is removed by hemodialysis, the patient should be given an additional dose of 250 mg after this procedure to avoid an increase in blood pressure. Children and adolescents under 18 years of age The recommended initial dose in children is 10 mg/kg body weight per day in 2 to 4 doses. If necessary, the daily dose can be gradually increased (up to 65 mg/kg body weight) at intervals of at least two days. The daily dose should not exceed 3000 mg. The dose of the drug and duration of treatment are determined by the doctor individually depending on the clinical condition of the patient. Side effects Very common (≥ 1/10) - positive Coombs test Rare (≥ 1/10,000 and <1/1000) - hemolytic anemia, leukopenia, granulocytopenia, thrombocytopenia Very rare (<1/10,000) - myocarditis, pericarditis - parkinsonism - increased angina - pancreatitis - hepatitis, liver necrosis Not known (frequency cannot be estimated from available data) - bone marrow suppression, positive test for antinuclear antibodies, LE cells, rheumatoid factor - hyperprolactinemia, gynecomastia, galactorrhea, amenorrhea - nightmares, usually unexpressed, transient psychosis or depression, decreased libido - peripheral paresis of the facial nerve, lethargy, involuntary choreoathetotic movements, symptoms of cerebrovascular insufficiency (possibly associated with hypotension), headache, sedation (usually transient), apathy, weakness, dizziness, paresthesia - congestive heart failure, sinus bradycardia, edema, weight gain. Edema and weight gain usually respond well to diuretics. If edema becomes more pronounced, as well as when symptoms of heart failure appear, treatment with the drug should be discontinued - increased sensitivity of the carotid sinus, orthostatic hypotension (a dose reduction is recommended) - nasal congestion - colitis, vomiting, inflammation of the salivary glands, soreness or blackening of the tongue, nausea , constipation, flatulence, dry mouth - cholestasis, jaundice, liver function test disorders - toxic epidermal necrolysis, eczema, lichenoid eruptions - impotence, ejaculation disorders - increased residual blood nitrogen Contraindications - hypersensitivity to the active or other components of the drug - liver dysfunction associated with previous use of methyldopa - active stage of liver disease (active hepatitis or active cirrhosis) - concomitant therapy with monoamine oxidase inhibitors - depression - pheochromocytoma - children under 18 years of age. Drug interactions Dopegit should not be used simultaneously with monoamine oxidase inhibitors. Concomitant use with the following drugs requires special caution: Drugs that reduce the hypotensive effect of Dopegit: - sympathomimetics - tricyclic antidepressants - phenothiazines (at the same time, an additive hypotensive effect is possible) - oral iron preparations (ferrous sulfate and gluconate/II) (may reduce the bioavailability of methyldopa) - non-steroidal anti-inflammatory drugs - estrogen drugs · Drugs that enhance the hypotensive effect of the drug Dopegit: - other antihypertensive drugs (summation of hypotensive effects is possible) - anesthetics Dopegit and the following drugs can change the effects of each other: - lithium preparations (possible development of lithium intoxication ) - levodopa (reduced antiparkinsonian effect and increased undesirable effect on the central nervous system) - ethanol and other drugs that depress the central nervous system (increased depression of the central nervous system) - anticoagulants (increased anticoagulant effect, risk of bleeding) - bromocriptine (possibly undesirable effect on concentration of prolactin) - haloperidol (possible impairment of cognitive functions - disorientation and confusion). Special instructions During treatment with drugs containing methyldopa, hemolytic anemia may develop in rare cases. If symptoms indicating hemolytic anemia develop, it is necessary to determine the hematocrit and hemoglobin level. If anemia is confirmed, further studies should be performed to confirm hemolysis. If hemolytic anemia is confirmed, methyldopa should be discontinued immediately. After discontinuation of the drug, hemolytic anemia quickly resolves without or with the help of corticosteroid treatment. In rare cases, fatalities have been observed. If hemolytic anemia is caused by taking methyldopa, the patient should not continue to receive this drug. In some patients, with long-term use of Dopegyt, a positive Coombs test may be observed. A positive Coombs test, according to the literature, can occur in 10 - 20% of patients receiving this drug. A positive Coombs test is rarely observed during the first 6 months of treatment. If it does not develop within 12 months, then its development is unlikely with further use of this drug. A positive Coombs test is dose-dependent and is unlikely to develop at doses less than 1 g/day. A positive Coombs test that developed during treatment with Dopegyt may become negative only a few weeks or months after discontinuation of the drug. Before starting the course of treatment, as well as at 6 and 12 months of treatment with Dopegyt, the number of blood cells should be examined and a direct Coombs test should be performed. The mere presence of a previous positive Coombs test or its occurrence in a patient during treatment is not a contraindication to Dopegyt therapy. If the Coombs test becomes positive during treatment with Dopegyt, the presence of hemolytic anemia and the degree of clinical significance of a positive Coombs test should be checked. Information about the presence of a positive Coombs test helps in the evaluation of cross-blood compatibility testing. If a blood transfusion is necessary in a patient receiving Dopegyt, direct and indirect Coombs tests should be performed. In the absence of hemolytic anemia, only the direct Coombs test is usually positive. The direct Coombs test itself does not affect blood typing or crossmatching. If the indirect Coombs test is also positive, consultation with a hematologist or transfusiologist is necessary. During treatment, rare cases of leukopenia, granulocytopenia and thrombocytopenia are possible. Typically, the granulocyte count normalizes after discontinuation of methyldopa. Thrombocytopenia is also reversible. In some cases, fever may occur, accompanied by eosinophilia and liver dysfunction. Jaundice may also develop with or without fever. These symptoms usually develop in the 2nd – 3rd month of treatment. In some cases, the symptoms were found to be due to cholestasis. Biopsies were taken from some patients with liver dysfunction. Histological examination revealed focal necrosis, characteristic of a hypersensitivity reaction. Before starting treatment with Dopegyt and during the first 6–12 weeks of treatment, as well as at any time with the development of fever of unknown etiology, tests to determine liver function, as well as qualitative and quantitative blood tests are recommended. Therefore, if fever, changes in the activity of liver enzymes or jaundice occur, the course of treatment with Dopegyt should be stopped immediately. If this condition is caused by a hypersensitivity reaction, the increase in temperature and changes in laboratory parameters disappear after discontinuation of the drug. Such patients should not be prescribed Dopegit in the future. This drug should be given with extreme caution to patients with a history of liver disease or impairment. Patients receiving Dopegyt may require reduced doses of anesthetics. If hypotension occurs during anesthesia, vasoconstrictor drugs can be administered to correct it. Adrenergic receptors remain sensitive when using methyldopa. Some patients may experience swelling or weight gain while taking Dopegyt; in these conditions, diuretics should be prescribed. Treatment with Dopegyt should not be continued if edema increases or symptoms of heart failure develop. Methyldopa is eliminated by dialysis. Therefore, after this procedure, blood pressure in patients on hemodialysis may increase. In rare cases, involuntary choreoathetotic movements may occur in patients with severe bilateral cerebral vascular disease. In this case, treatment should be discontinued. Extreme caution is required when prescribing Dopegyt to patients with hepatic porphyria or their close relatives. Dopegit can change the results of the analysis of uric acid in urine using the phosphotungstic acid method, the determination of serum creatinine by the alkaline picrate method, and the colorimetric determination of the AST enzyme. To date, there is no evidence that methyldopa changed the results of spectrophotometric determination of AST. Since methyldopa fluoresces at the same wavelength as catecholamines, the use of Dopegyt may give pseudo-positive results; high concentrations of catecholamines may be detected in the urine, which interferes with the diagnosis of pheochromocytoma. However, methyldopa does not affect the results of measurements of VMA (vanillyl mandelic acid) in urine. Drinking alcohol is not recommended during treatment. Pregnancy and lactation For arterial hypertension in pregnant women, the drug should be prescribed after careful medical supervision. Available data showed no evidence of harm to the fetus or newborn. The drug can be prescribed to pregnant women, women planning pregnancy and women who have the possibility of pregnancy, only in cases where the expected benefit of treatment outweighs the possible risk. Methyldopa passes through the placenta and is detected in the blood of the umbilical cord and in breast milk. Dopegit can be prescribed to nursing mothers only after careful comparison of the expected benefits of treatment and the possible risks. Features of the effect of the drug on the ability to drive a vehicle and potentially dangerous mechanisms Dopegit may have a sedative effect, which is usually transient and can be observed either at the beginning of treatment or when the dose is increased. If patients develop symptoms indicating the development of sedation, they are prohibited from driving a vehicle or performing work that requires concentration. Overdose Symptoms: severe arterial hypotension, bradycardia, drowsiness, weakness, dizziness, nausea, vomiting, intestinal atony, flatulence, constipation, diarrhea. Treatment: symptomatic treatment - gastric lavage, stimulation of vomiting (if the drug has been taken recently). After absorption of the drug, its excretion through the kidneys can be stimulated by administering fluids. Monitoring of heart rate, cardiac output and blood volume, electrolyte balance, bowel and renal function, and brain function is required. According to indications, sympathomimetics (for example, adrenaline) are prescribed. If a chronic overdose is suspected, the drug Dopegit should be discontinued. Release form and packaging 50 tablets are placed in brown glass bottles with polyethylene caps, with first-opening control and equipped with an accordion shock absorber. One bottle each along with instructions for medical use in the state and Russian languages in a cardboard pack. Storage conditions Store at a temperature not exceeding 25°C. Keep out of the reach of children! Shelf life: 5 years Do not use after expiration date. Conditions for dispensing from pharmacies By prescription 1106 BUDAPEST, st. Keresturi, 30-38 Hungary Phone: (36-1) 803-5555, fax: (36-1) 803-5529 Registration certificate owner JSC "EGIS Pharmaceutical Plant", Hungary Address of the organization accepting claims from consumers on the territory of the Republic of Kazakhstan quality of products (goods) Representative office in the Republic of Kazakhstan CJSC "EGIS Pharmaceutical Plant" 050060, Almaty, st. Zharokova 286 G tel: +, +, fax: + 7 (727) 247 61 41 e-mail
Side effects of the drug Dopegit
From the cardiovascular system: peripheral edema, orthostatic hypotension, bradycardia. From the side of the central nervous system: headache, dizziness, weakness, drowsiness, rarely - parkinsonism syndrome, hallucinations. From the gastrointestinal tract: nausea, vomiting, dry mouth, diarrhea, constipation, pancreatitis, liver dysfunction, jaundice, colitis. From the hematopoietic system: rarely - leukopenia and thrombocytopenia, autoimmune hemolytic anemia. From the endocrine system: gynecomastia, galactorrhea, decreased libido, impotence. Allergic reactions: exanthema. Rarely - fever, myalgia, arthralgia, lupus syndrome.
Pharmacological properties of the drug Dopegit
A drug that acts on the central mechanisms of blood pressure regulation. Penetrates the blood-brain barrier; metabolized to form alpha-methylnorepinephrine, which stimulates postsynaptic alpha-adrenergic receptors of brain stem neurons in the central nervous system, which leads to inhibition of the vasomotor center. The hypotensive effect with long-term use of the drug is mainly associated with a decrease in peripheral vascular resistance, while the minute blood volume does not change. Increases glomerular filtration rate and renal circulation, reduces the level of renin in blood plasma. It also causes a moderate decrease in cardiac output and heart rate. The effect of the drug appears 2 hours after use and lasts 24–48 hours. After oral administration, about 50% of the drug is absorbed into the gastrointestinal tract. Protein binding - up to 20%. Up to 10% of the dose taken is metabolized to form alpha-methyldopa and alpha-methylnorepinephrine. It is excreted mainly by the kidneys. About 70% of the absorbed drug is excreted in the urine in the form of methyldopa and its sulfoconjugates. With long-term use, the drug can accumulate in the body. The half-life is no more than 8 hours; with renal failure - increases. After oral administration, complete elimination of the drug occurs after 36 hours. It is removed by hemodialysis and peritoneal dialysis.
Overdose of the drug Dopegit, symptoms and treatment
Symptoms: severe arterial hypotension, tremor, bradycardia, gastric atony, vomiting, mental retardation. Treatment: gastric lavage (if the drug was taken recently); if detoxification is carried out with a significant delay, the use of hemodialysis is more effective than the method of forced diuresis. According to indications, plasma-substituting solutions and adrenomimetics (for example, epinephrine) are prescribed. In case of an overdose of Dopegyt tablets, you should immediately consult a doctor at the nearest emergency room or hospital.
Special instructions for the use of the drug Dopegit
The drug should be used with extreme caution in patients with cerebrovascular accidents; history of depression; Parkinson's disease (possible exacerbation). If you have kidney disease, before using Dopegyt, you should conduct an examination to determine the presence of renal failure. During the first 1–3 months of treatment, it is recommended to periodically monitor the hemogram and the level of hepatic transaminases in the blood serum. After the first 6–10 weeks of treatment, it is necessary to exclude the possibility of autoimmune hemolytic anemia (Coombs test), which during long-term treatment must be repeated every 6 months–1 year. When treated with methyldopa, a positive catecholamine test may appear, indicating the possibility of developing pheochromocytoma. Administration of Dopegyt at a dose of ≥750 mg/day can also lead to a positive porphobilinogen test. Due to the effect of the drug on water balance, peripheral edema may occur, which sometimes requires the use of diuretics. Since edema is the most common side effect when using the drug Dopegit, during the treatment period it is necessary to ensure control of the patients’ body weight, drinking and dietary regimen. With general anesthesia, the narcotic effect may be enhanced. During pregnancy, women taking Dopegit do not have to stop taking it. The use of Dopegit in this case should be carefully weighed taking into account the balance of benefits for the mother with the potential risk for the child. Methyldopa passes into breast milk, therefore, when prescribing Dopegyt, the patient must stop breastfeeding. During the treatment period, you should avoid drinking alcoholic beverages. It is necessary to refrain from potentially hazardous activities that require concentration, including driving.
Drug interactions Dopegit
Caution should be exercised when taking Dopegit in combination with any of the following drugs:
- levodopa, levadopa/cardipopa - may enhance the antihypertensive effect;
- drugs belonging to the group of MAO inhibitors (for example, phenelzine, transcipromine) - may increase hypotension or hypertension with psychomotor agitation;
- drugs for the treatment of patients with depression (for example, tricyclic antidepressants) - decreased antihypertensive effect, the appearance of tachycardia, agitation, headache;
- diuretics, apressin, calcium antagonists, ACE inhibitors, β-adrenergic receptor blockers, α-adrenergic receptor blockers or other antihypertensive drugs, as well as anesthetics enhance the effect of Dopegit;
- digoxin - possible appearance of bradycardia, asystole;
- Iron supplements weaken the effect of Dopegit;
- indomethacin and other NSAIDs reduce the antihypertensive effect of Dopegit;
- lithium - increased toxicity of lithium is possible;
- alcohol and drugs that cause central nervous system depression increase the depressive effect;
- anticoagulants derivatives of coumarin and indadione increase the anticoagulant effect;
- anorexigenic drugs weaken the effect of Dopegit;
- sympathomimetics dopamine, mesaton enhance the effect of Dopegit.
The combination of Dopegyt with tranquilizers increases the antihypertensive effect. With urine alkylation, the concentration of Dopegyt in the blood increases, with acidolization, the effect decreases. The use of Dopegit in combination with any of these drugs may change their effect on the body or be dangerous to the body.
