Index of drugs

Hypertension.

1 tabl contains 250 mg of methyldopa.

Antihypertensive drug with central effect. After penetrating to o.u.n. exerts its hypotensive effect through its active metabolite (alphamethylradadrenaline) by: reducing the sympathetic nervous system (by stimulating central, presynaptic α-inhibitory receptors₂), acting as a false neurotransmitter replacing endogenous Dopamine on dopaminergic nerve endings, reducing plasma renin activity and peripheral vascular resistance, inhibiting the enzyme DOPA decroxylase (reducing the synthesis of noradrenaline, Dopamine, serotonin and concentrations of noradrenaline and adrenaline in tissues). It lowers blood pressure in both lying and standing position. Bioavailability is about 25%. The maximum effect occurs after 4-6 h and lasts for approx. 12-24 h. To a small extent (<20%) is associated with plasma proteins, it is extensively metabolised in the liver. The active alphamethyl adrenaline metabolite is formed in adrenergic neurone centers. About 1/3 of absorbed methyldopa is excreted unchanged in the urine or in the form conjugated with sulphate, the rest is removed with faeces as methyldopa. T_0,5 is 1.8 + 0.2 hours.

Hypersensitivity to methyldopa or other components of the drug. Active liver disease (eg acute hepatitis, liver cirrhosis). Methyldopa-induced liver disease history. Simultaneous treatment with MAO inhibitor. Depression. Phaeochromocytoma.

If haemolytic anemia is diagnosed, the drug should be discontinued. Discontinuation of therapy usually led to rapid remission. However, there have rarely but been fatal cases. Methyldopa must never be administered to a patient if methyldopa has previously been found to induce hemolytic anemia. A positive Coombs test rarely occurs during the first 6 months of therapy and if it does not appear within 12 months, it is unlikely to occur during further therapy. The Coombs positive test is related to the size of the dose, which is the least common for patients taking ≤1g per day. A positive Coombs test result that occurred during therapy becomes negative after a few weeks or months after the end of treatment. Before starting the therapy, and then at its 6th and 12th month, it is recommended to perform a morphology and a direct Coombs test. Previous positive results or obtaining a positive result in a direct Coombs test are not a contraindication for further methyldopa therapy. If the positive Coombs test result appears during methyldopa therapy, it should be verified if there is hemolytic anemia and if the Coombs test positive is important in the treatment. Prior knowledge of a positive Coombs test result will help in the assessment of the cross-check required for transfusion. If you need a blood transfusion in a methyldopa-treated patient, you must have both a direct and indirect Coombs test before the procedure. In the absence of haemolytic anemia, only a direct Coombs test will be positive. The positive result of the Coombs direct test does not in itself interfere with the determination of the blood group or the cross-over test. A positive result of an indirect Coombs test may cause difficulties in the cross-over evaluation; in this case, a hematologist or transfusionist will be needed. Very rarely, liver necrosis can lead to death. Liver function tests and morphology with complete and differentiated white blood cell picture are recommended before initiation of methyldopa therapy and during the 6th and 12th weeks of treatment, as well as in the case of unexplained fever. In the event of fever, abnormal liver function or jaundice, treatment should be discontinued immediately. Methyldopa should not be re-used in these patients. In patients with a history of hepatic disease and dysfunction, methyldopa should be used with extreme caution. In patients taking methyldopa, lower doses of anesthetics should be used. If hypotension occurs during anesthesia, vasopressants should be used.Adrenergic receptors remain susceptible during treatment with methyldopa. Some patients may experience swelling and weight gain when taking methyldopa, which can be treated with diuretics. Do not continue treatment with methyldopa if the edema worsens or if you develop symptoms of heart failure. Methyldopa is removed during dialysis and therefore high blood pressure may occur again after the procedure. Patients with bilateral cerebrovascular disease may occasionally have involuntary choreoathetotic movements. In this case, methyldopa treatment should be discontinued. Take special care with methyldopa in patients with hepatic porphyria and their close relatives. Do not consume alcoholic beverages during therapy.

Methyldopa has been used under strict medical supervision to treat hypertension during pregnancy. No clinical evidence was found suggesting its harmful effects on the fetus or newborn. Published reports on the use of methyldopa in all trimesters indicate that fetal harm associated with the use of this medicine is unlikely. Methyldopa passes through the placental barrier and appears in umbilical cord blood and breast milk. Although no teratogenic effects have been identified, the possibility of fetal damage can not be excluded. Therefore, the drug should not be used by pregnant women who may become pregnant, plan to become pregnant or breastfeeding, if the expected benefits of treatment do not outweigh the potential risks.

Very often: a positive Coombs test. Rare: hemolytic anemia, leukopenia, granulocytopenia, thrombocytopenia. Very rare: myocarditis, pericarditis, parkinsonism, exacerbation of angina pectoris, congestive heart failure, hypersensitivity of the carotid sinus, orthostatic hypotension (dose reduction recommended), sinus bradycardia, edema, weight gain, pancreatitis, hepatitis. Not known: bone marrow depression, positive results for antinuclear antibodies, LE cells and rheumatoid factor, vasculitis, lupus-like syndrome, drug-induced fever, eosinophilia, hyperprolactinaemia, gynaecomastia, galactorrhea, amenorrhea, spontaneous facial nerve palsy, choreathetical movements, cerebral circulation disorders , mental disorders (nightmares, mild psychoses, depression), headache or dizziness, sedation, asthenia or asthenia, paresthesia, decreased libido, nasal congestion, enteritis, diarrhea, salivary glands, pain or black tongue, nausea, constipation, flatulence, gases, dry mouth, toxic skin necrosis, eczema or lichen, cholestasis, jaundice, hepatic enzyme disorders, mild joint pain with or without edema, muscle pain, impotence, ejaculation disorders, increase in blood urea nitrogen. At the beginning of treatment or when increasing the dose may occur: transient drowsiness, headache and weakness.

Orally. Dosage is determined individually for each patient. Adults: The initial dose is usually 250 mg 2-3 times a day during the first 2 days. The dose can be gradually increased or decreased, depending on the degree of reduction of blood pressure, at intervals of not less than 2 days. Because a sedative effect may occur, it is recommended to increase the evening dose first for 2-3 days at the beginning of treatment and during dose escalation. Typically, the maintenance dose is 500-2 g per day, administered in 2-4 doses. The maximum daily dose is 3 g. If the reduction in blood pressure is unsatisfactory after using 2 g methyldopa daily, combination therapy with other antihypertensives is recommended. After 2 or 3 months of treatment, tolerance may develop. Effective pressure control can be restored by increasing the dose of methyldopa or by adding a diuretic. Blood pressure generally returns to the original pre-therapy level after discontinuing methyldopa within 48 h without a withdrawal reaction. Methyldopa therapy can be started in patients already during treatment with other antihypertensive agents, gradually reducing the dose of antihypertensive drugs. In such cases, the initial daily dose should not exceed 500 mg and should be increased if necessary at intervals of not less than 2 days.Elderly patients: treatment should be started with the lowest possible dose, not exceeding 250 mg daily. If necessary, the dose can be gradually increased at intervals of not less than 2 days. Fainting that occurs more frequently in the elderly and which may be associated with increased sensitivity and advanced atherosclerosis can be prevented by using smaller doses. Patients with impaired renal function: lower doses are needed. In mild renal failure (GFR 60-89 ml / min / 1.73 m²) the dose interval should be extended to 8 hours; in moderate renal failure (GFR 30-59 ml / min / 1.73 m²) up to 8-12 hours; in severe renal failure (GFR <30 ml / min / 1.73 m²) up to 12-25 h. Methyldopa is removed during dialysis, therefore, after the procedure, to avoid increased blood pressure should be given a supplemental dose of 250 mg. Children: the initial daily dose is 10 mg / kg. in 2-3 doses. If necessary, the daily dose may be gradually increased at intervals of not less than 2 days until an adequate response is obtained. The maximum daily dose is 65 mg / kg, with no more than 3 g per day. The tablets can be taken before or after a meal.