Dopegit, tablets 250 mg 50 pcs

Pharmgroup:

Hypertensive drug of central action.

Pharm Action:

Dopegit is an antihypertensive drug of central action. It is metabolized to form alpha-methylnoradrenaline, which has a hypotensive effect through several mechanisms:

reduction of sympathetic tone by stimulation of central inhibitory presynaptic α2-receptors;

substitution of endogenous dopamine at dopaminergic nerve endings-as a false neurotransmitter;

reduction of plasma renin activity and OPPS;

suppression of the enzyme dopa decarboxylase, which leads to decreased synthesis of noradrenaline, dopamine, serotonin and tissue concentrations of noradrenaline and adrenaline.

Methyldopa 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, filtered fraction. In some cases the HR is reduced. It reduces BP both when lying and standing, only rarely causes orthostatic hypotension.
Maximum BP reduction occurs 4-6 hours after oral administration and lasts 12-24 hours. After repeated use, the maximum hypotensive effect develops within 2-3 days. After discontinuation of the drug BP returns to the initial level within 1-2 days.

Pharmacokinetics:

Intake

About 50% of alpha-methyldopa is absorbed after oral administration.

Distribution

Little (less than 20%) is bound to plasma proteins. Methyldopa penetrates the placental barrier and is excreted with breast milk.

Metabolism

Metabolized in the liver to form the active metabolite alpha-methylnoradrenaline and other metabolites.

Elimination

Extracted mainly with the urine. About 70% of the absorbed active ingredient is excreted in the urine as methyldopa and its sulfoconjugates, the remainder is excreted in the feces as methyldopa.

In normal renal function the T1/2 is 1.7 h. The active component of the drug is completely eliminated from the body within 36 hours.
Pharmacokinetics in special clinical cases

In renal failure, excretion of methyldopa is slower according to the degree of renal impairment. In severe renal impairment (without hemodialysis) the T1/2 of methyldopa is increased by a factor of 10.

Methyldopa is excreted by hemodialysis. A 6-hour hemodialysis can eliminate 60% of the absorbed dose of methyldopa from the circulating blood; peritoneal dialysis for 20-30 h eliminates approximately 22-39%.

Indications

Arterial hypertension.

Pharmacological effect

Pharmaceutical group:

centrally acting antihypertensive agent.

Pharmaceutical action:

Dopegit is a centrally acting antihypertensive drug. Metabolized to form alpha-methylnorepinephrine, which has a hypotensive effect through several mechanisms:

reduction of sympathetic tone by stimulation of central inhibitory presynaptic α2 receptors;

replacement of endogenous dopamine at dopaminergic nerve endings – as a false neurotransmitter;

decreased plasma renin activity and peripheral vascular resistance;

suppression of the enzyme dopa decarboxylase, which leads to a decrease in the synthesis of norepinephrine, dopamine, serotonin and the concentration of norepinephrine and adrenaline in tissues.

Methyldopa does not have a direct effect on cardiac function, does not reduce cardiac output, does not cause reflex tachycardia, and does not reduce the glomerular filtration rate, renal blood flow, or filtered fraction. In some cases, heart rate decreases. Reduces blood pressure both in the supine and standing positions, only in rare cases causing orthostatic hypotension.
The maximum decrease in blood pressure occurs 4-6 hours after oral administration and lasts 12-24 hours. After repeated administration, the maximum hypotensive effect develops within 2-3 days. After discontinuation of the drug, blood pressure returns to its original level within 1-2 days.

Pharmacokinetics:

Suction

After oral administration, approximately 50% of alpha-methyldopa is absorbed.

Distribution

Slightly (less than 20%) binds to blood plasma proteins. Methyldopa crosses the placental barrier and is excreted in breast milk.

Metabolism

Metabolized in the liver to form an active metabolite – alpha-methylnorepinephrine and other metabolites.

Removal

It is excreted mainly in the urine. About 70% of the absorbed active substance is excreted in the urine in the form of methyldopa and its sulfoconjugates, the rest is excreted in the feces in the form of methyldopa.

With normal renal function, T1/2 is 1.7 hours. The active component of the drug is completely eliminated from the body within 36 hours.
Pharmacokinetics in special clinical situations

In renal failure, the elimination of methyldopa slows down according to the degree of renal dysfunction. In case of severe renal impairment (without hemodialysis), T1/2 of methyldopa increases 10 times.

Methyldopa is eliminated during hemodialysis. 6-hour hemodialysis can remove 60% of the absorbed dose of methyldopa from the circulating blood, peritoneal dialysis for 20-30 hours removes approximately 22-39%.

Active ingredient

Methyldopa

Composition

1 tablet contains methyldopa sesquihydrate 250 mg.

Pregnancy

The results of clinical studies did not reveal signs of damage to the newborn or fetus when using the drug in the second and third trimesters of pregnancy.

However, it is recommended to prescribe the drug Dopegit to pregnant women only under strict indications.

Contraindications

– acute hepatitis, cirrhosis of the liver;
– history of liver disease (while taking methyldopa);
– concomitant therapy with MAO inhibitors;
— depression;
– hemolytic anemia;
— acute myocardial infarction;
— pheochromocytoma;
– hypersensitivity to the drug Dopegit.
The drug should be prescribed with caution in case of renal failure (dose adjustment required), diencephalic syndrome, elderly patients and children.

Side Effects

When using Dopegit, the following may occur:

– lethargy, drowsiness, lethargy, facial nerve paralysis, parkinsonism, paresthesia, spontaneous chorioathetoid movements, staggering when walking, dizziness, headache;
– orthostatic hypertension, peripheral edema, bradycardia, hyperemia of the upper half of the body, worsening heart failure, increased angina, in rare cases – pericarditis, myocarditis;
– glossalgia, dryness of the oral mucosa, vomiting, nausea, diarrhea, colitis, hepatotoxicity, pancreatitis, jaundice, increased activity of liver transaminases;
– leukopenia, hemolytic anemia, agranulocytosis, thrombocytopenia;
– arthralgia, myalgia;
– galactorrhea, gynecomastia, hyperprolactinemia;
– decreased libido, decreased potency, amenorrhea;
– fever, rash, exanthema, toxic epidermal necrolysis (Lyell’s syndrome);
– inflammation of the salivary glands, nasal congestion;
– positive direct Coombs test (when taking the drug for more than 6 months at a daily dosage of >1 g).

Interaction

The combination of the drug with MAO inhibitors can lead to increased side effects: arterial hypotension or hypertensive crisis with psychomotor agitation.

Combination with tricyclic antidepressants can reduce the hypotensive effect of the drug and provoke the appearance of headaches, tachycardia, and agitation.

Combined use with levodopa can lead to an increase in the antiparkinsonian effect, which is due to the inhibition of peripheral decarboxylation of levodopa under the influence of methyldopa and an increase in the concentration of levodopa in the central nervous system. In cases where inhibition of decarboxylation predominates in the central nervous system, the antiparkinsonian effect of levodopa decreases.

The combination of Dopegyt with drugs that contain levodopa + carbidopa can lead to the development of orthostatic hypotension. In such cases, patients are recommended to remain in a horizontal position for 1-2 hours after taking the drugs.

The combination of Dopegit with haloperidol leads to an increased likelihood of developing dementia; combination with digoxin in elderly patients can lead to an increased likelihood of developing SSSS.

To increase the hypotensive effect of the drug, it is advisable to combine it with diuretics, hydralazine and nifedipine.
Concomitant use of the drug with beta-blockers can lead to the development of orthostatic hypotension.

Simultaneous use with adrenomimetics, indomethacin and other NSAIDs leads to a decrease in the severity of the hypotensive effect of the drug.

The combination of Dopegit with anxiolytics (tranquilizers) enhances the hypotensive effect of the drug.

Alkalinization of urine during methyldopa therapy leads to an increase in its effect, acidification of urine leads to a decrease in effect.
The drug should be stopped 7-10 days before general anesthesia to avoid the development of a collapsoid state.

Drugs for general anesthesia (sodium thiopental or halothane) should be used cautiously in patients taking methyldopa. The use of diethyl ether is contraindicated.

Dopegit increases the hepatotoxicity of oral contraceptives and lithium salts.

The drug is incompatible with reserpine.

Caution should be exercised when combining Dopegyt with quinidine, antipsychotics, acetazolamide and procainamide.

Overdose

In case of an overdose of the drug Dopegit, severe arterial hypotension, weakness, severe bradycardia, drowsiness, tremor, lethargy, dizziness, flatulence, constipation, diarrhea, vomiting, nausea, and intestinal atony may develop.

Treatment of overdose: soon after administration, rinse the stomach and stimulate vomiting in order to reduce the amount of absorbed drug. It is advisable to monitor blood volume, heart rate, electrolyte balance, kidney, intestinal and brain functions. Sympathomimetics (epinephrine) can be administered if necessary.

Storage conditions

Store at a temperature of 15-25 degrees Celsius.

Manufacturer

EGIS, Hungary