DOPEGIT

Active material: Methyldopa
When ATH: C02AB01
CCF: Stimulant of the central alpha₂-adrenoreceptorov. Antihypertensive drugs
ICD-10 codes (testimony): I10
When CSF: 01.09.01.01
Manufacturer: EGG PHARMACEUTICALS Plc (Hungary)

Pharmaceutical form, composition and packaging

Pills white or grayish-white, round, flat, chamfered, smooth on one side, on the other side – etching “DOPEGYT”, with little or no odor.

Excipients: ethyl cellulose, magnesium stearate, corn starch, stearic acid, sodium carboxymethyl (Type A), talc.

50 PC. – brown glass vials (1) – packs cardboard.

Pharmacological action

Antihypertensive medications central action. It is metabolized to form alpha-metilnoradrenalina, which has a hypotensive effect through several mechanisms:

- Decrease in sympathetic tone by stimulating the central inhibitory presynaptic α₂-receptors;

- Replacement of endogenous dopamine in the dopaminergic nerve terminals – as a false neurotransmitter;

- Decrease in plasma renin activity and PR;

- Suppression of the enzyme dopa decarboxylase, which leads to a decrease in the synthesis of noradrenaline, dopamine, serotonin and noradrenaline and adrenaline in the tissues.

Methyldopa has no direct effect on cardiac function, It does not reduce cardiac output, It does not cause reflex tachycardia, and does not reduce the rate of glomerular filtration, renal blood flow, filterable fraction. In some cases, reduced heart rate. It reduces blood pressure in the supine position, and standing, only in rare cases it causes orthostatic hypotension.

The maximum reduction in blood pressure occurs within 4-6 hours after ingestion and continues 12-24 no. After repeated administration the maximum antihypertensive effect develops within 2-3 days. After discontinuation of blood pressure returned to baseline within 1-2 days.

Pharmacokinetics

Absorption

After ingestion absorbed about 50% alpha-methyldopa.

Distribution

Insignificantly (less 20%) bound to plasma proteins. Methyldopa crosses the placental barrier and is excreted in breast milk.

Metabolism

It is metabolized in the liver to the active metabolite – alpha and other metabolites metilnoradrenalina.

Deduction

Write mainly in the urine. About 70% of absorbed active substance is excreted in the urine as methyldopa and its sulfokonyugatov, the remainder is excreted in the feces in the form of methyldopa.

In normal kidney function T_1/2 is equal to 1.7 no. The active ingredient of the drug is completely eliminated from the body within 36 no.

Pharmacokinetics in special clinical situations

In renal insufficiency excretion dopegyt slows down according to the degree of renal impairment. In severe renal dysfunction (hemodialysis) T_1/2 methyldopa increases 10 time.

Methyldopa appear in hemodialysis. 6-hour hemodialysis may withdraw from the circulating blood 60% suck dose methyldopa, for peritoneal dialysis 20-30 h brings about 22-39%.

Testimony

- Arterial hypertension.

Dosage regimen

The tablets are taken orally before or after food. The mode set individually.

Adults appointed in the first 2 the day on 250 mg (1 tab.) 2-3 times / day, then the daily dose is gradually increased or decreased (every 2 of the day on 250 mg) depending on the severity of BP reduction. To reduce the severity of sedation at first increase the evening dose. The maintenance dose is 0.5-2 g / day 2-4 admission.

The maximum daily dose is 2 g. If you are taking the drug at a dose of 2 g / day have not been effective blood pressure reduction, recommended dopegit^® in combination with other antihypertensives.

After 1-3 months of treatment may develop tolerance. Effective control of blood pressure can be restored by the addition of a diuretic or increasing the dose Dopegita^®.

To patients Seniors initial dose should be as low as possible, no more 250 mg 2 times / day, tk. they often arises sedation. If necessary, the dose may be increased every 2 day to a maximum daily dose 2 g, which may not be exceeded.

Patients with impaired renal function Dosage adjustment. At renal failure mild (glomerular filtration rate (SKF) > 50 ml / min) should withstand the interval between doses 8 no, at renal failure moderate (SKF = 10-50 ml / min) the interval should be 8-12 no, and when severe renal insufficiency (SKF < 10 ml / min) – 12-24 no.

Since methyldopa removed by hemodialysis, After this procedure, the patient must take an additional dose 250 mg in order to avoid increase blood pressure.

The recommended starting dose Dopegita^® in children is 10 mg / kg body weight / day 2-4 admission. If necessary, the daily dose can be gradually increased (up to a maximum 65 mg / kg body weight) at intervals of no less than two days.

Side effect

From the central and peripheral nervous system: at the beginning of treatment or after dose escalation – transient sleepiness, headache, and weakness; perhaps – paresthesia, dizziness, anxiety, depression, psychosis (mild and transient), nightmares, rarely – parkinsonizm, Choreoathetosis, symptoms of cerebrovascular insufficiency (perhaps, associated with hypotension), peripheral facial nerve paresis.

Cardio-vascular system: increased angina pectoris, worsening symptoms of congestive heart failure, sinusovaya bradycardia, reducing the sensitivity of the carotid sinus, orthostatic hypotension, peripheral edema, weight gain, rarely – miokardit, perikardit.

From the digestive system: pancreatitis, colitis, vomiting, diarrhea, inflammation of the salivary glands, ulceration or blackening language, nausea, constipation, flatulence, dry mouth, jaundice, hepatitis, cholestasis, increase in liver enzymes.

From the side of hematopoiesis: bone marrow depression, leukopenia, agranulocytosis, thrombocytopenia, gemoliticheskaya anemia, a positive test for antinuclear antibody, LE cells, rheumatoid factor, Coombs test positive; rarely – obratimaya leykopeniya and thrombocytopenia, gemoliticheskaya anemia.

Allergic reactions: vasculitis, symptoms, resembling SLE, fever, eozinofilija, toxic epidermal necrolysis (Lyell's syndrome), rash.

On the part of the endocrine system: hyperprolactinemia, gynecomastia, galactorrhea.

On the part of the reproductive system: amenorrhea, reduced potency and / or libido.

On the part of the musculoskeletal system: arthralgia, myalgia.

The respiratory system: nasal congestion.

Other: increase in residual nitrogen of blood.

Contraindications

- Acute hepatitis, cirrhosis of the liver;

- History of liver disease (while taking methyldopa);

- Concomitant therapy MAO inhibitors;

- Depression;

- Gemoliticheskaya anemia;

- Acute myocardial infarction;

- Pheochromocytoma;

- Hypersensitivity to the drug.

FROM caution should be prescribed in patients with renal insufficiency (Dosage adjustment), diencephalic syndrome, elderly patients and children.

Pregnancy and lactation

According to the results of clinical trials after application of methyldopa in the II and III trimester of pregnancy showed no evidence of damage to the fetus or newborn. As adequate and well-controlled studies in III trimester of pregnancy has not been carried out, it is recommended to use the drug only after a careful comparison of the expected benefit of therapy for the mother and the potential risk to the fetus.

A study of children, born to mothers, Accepted methyldopa after 26 weeks of gestation, showed no adverse effects of the drug. Pregnant, taking the drug in the III trimester, the fetus was better, than in women, not taking medication.

Methyldopa is excreted in breast milk, therefore prescribed the drug during lactation is recommended only after careful comparison of the expected benefit to the mother and the potential risk for the baby.

Cautions

European and Russian guidelines for treatment of high blood pressure as the drug methyldopa considered the first-line treatment of hypertension in pregnant women, tk. it is characterized by the best security and does not cause adverse reactions in the mother and fetus.

Extreme care is required when assigning Dopegita^® patients with hepatic porphyria, or their close relatives.

During treatment requires monitoring of liver function and pattern of peripheral blood.

Before starting treatment Dopegitom^® should investigate the number of blood cells, and during the first 6-10 weeks of therapy, perform direct Coombs test, which then must be repeated every six months or a year. A positive Coombs test can have 10-20% patients, receiving the drug, especially after receiving a 1 Mr. Dopegita^® daily for six months, or one year. Less than 5% These patients may develop hemolytic anemia. In this case, it is necessary to immediately stop taking Dopegita^®. After discontinuation hemolytic anemia stops. If this does not occur, It requires the use of corticosteroids or analysis of other possible causes of hemolytic anemia. If hemolytic anemia is caused by taking Dopegita^®, patient should continue to receive the drug. A positive Coombs test is negative after a few weeks or months after discontinuation of the drug.

The existence of a positive Coombs' test or the appearance of the patient is not a contraindication to therapy Dopegitom^®. If Coombs test becomes positive during treatment Dopegitom^®, It should establish the presence of hemolytic anemia and the extent of the clinical significance of a positive test Coombs. For Example, in addition to the positive direct Coombs test rarely observed a positive indirect Coombs test, which may affect the blood crossmatch. If necessary, a blood transfusion to a patient, receiving dopegit^®, should be made direct and indirect Coombs test. In the absence of hemolytic anemia is usually only positive direct Coombs test. By itself, the direct Coombs test does not affect the typing or crossmatch blood. If the indirect Coombs test is also positive, should consult a specialist haematologist or TRANSFUSIOLOGY.

During the first 6-12 weeks of treatment, as well as in the event of fever of unknown etiology, should conduct monitoring of liver function. If you change the activity of liver transaminases or jaundice should assume the appearance of hypersensitivity reactions, at which a cholestasis, damage to liver cells or hepatitis. In very rare cases, it may be lethal liver necrosis. Therefore, a change in liver enzymes or symptoms of liver failure occurs treatment Dopegitom^® should cease immediately. Such patients should not be prescribed in the future dopegit^®.

Patients with a disease or disorder of the liver in the history of the drug should be used with extreme caution.

During treatment possibilities are very rare cases of agranulocytosis and thrombocytopenia. They usually disappear after canceling Dopegita^®.

In some patients, while receiving Dopegita^® may develop edema or weight gain; in these conditions should appoint diuretics. Treatment Dopegitom^® you can not continue with an increase in the development of edema or heart failure symptoms.

Methyldopa appears in dialysis. Therefore, after this procedure can increase blood pressure.

Since methyldopa has fluorescence in the same wavelength, as catecholamines, in the urine can be detected high concentrations of catecholamines, which hinders the diagnosis of pheochromocytoma. However, methyldopa does not affect the results of measurements of the WFC (vanillylmandelic acid).

Patients, receiving dopegit^®, should reduce the dose of drugs for general anesthesia. If during general anesthesia hypotension occurs, for its correction can be administered decongestants. Adrenergic receptors retain sensitivity treatment methyldopa.

In patients with severe bilateral lesions of cerebral vessels can rarely occur involuntary movements horeoatetoznye.

During the reception Dopegita^® Avoid drinking alcohol.

Effects on ability to drive vehicles and management mechanisms

In the initial, individually defined period of application Dopegita^® It is not allowed to drive a vehicle and engaging in other potentially hazardous activities, requiring quickness of psychomotor reactions. During the further treatment of the degree of limitation is determined depending on the individual patient response to the drug.

Overdose

Symptoms: severe hypotension, vыrazhennaya bradycardia, weakness, drowsiness, lethargy, tremor, dizziness, constipation, flatulence, diarrhea, nausea, vomiting, bowel atony.

Treatment: gastric lavage, stimulation of vomiting, taken shortly after taking the drug, can reduce the amount of the drug has grown deep. Necessary to control heart rate, OCK, electrolyte balance, intestinal and kidney function, and brain. If necessary, you can enter sympathomimetic (eg, epinephrine).

Drug Interactions

Dopegit^® should not be used in combination with MAO inhibitors due to increased adverse effects.

The combined use of Dopegita^® with sympathomimetics, tricyclic antidepressants, fenotiazinami, iron preparations for oral administration, NSAIDs, estrogen requires caution, since there is a reduction of antihypertensive action Dopegita^®.

In an application Dopegita^® with other antihypertensive agents, beta-blockers, General anesthetics, anxiolytics (trankvilizatorami) It is enhanced hypotensive effect Dopegita^®.

If concomitant use of levodopa Dopegitom^® may reduce protivoparkinsonicheskogo action of levodopa and strengthening undesirable effects on the central nervous system, and the joint application Dopegita^® combined with levodopa and carbidopa may develop orthostatic hypotension. In this case, after taking the drugs for patients should 1-2 h in a horizontal position.

In an application Dopegita^® with lithium may increase the toxicity of lithium.

In an application Dopegita^® with anticoagulants is intensified their actions, and there is a risk of bleeding.

In an application Dopegita^® with bromocriptine possible adverse effect on prolactin.

In an application Dopegita^® haloperidol may impair cognitive functions – disoriented and confused state of mind.

In an application Dopegita^® ethanol and other drugs, CNS depressants, there is a strengthening of depression.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at temperature from 15 ° to 25 ° C. Shelf life – 5 years.