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.

Active ingredient

Composition

1 tablet contains methyldopa sesquihydrate 250 mg.

How to take, the dosage

The drug Dopegit requires individual dosing.

Dopegit is given orally in an initial dosage of 250 mg in the evening (first two days) in adults. Over the next two days, the single dose is increased by 250 mg until the optimal hypotensive effect is achieved (usually seen when the daily dose of 1 g divided into 2-3 doses is reached).

In the first instance, it is recommended that the evening dose be increased to reduce the sedative effect.

The maximum daily dose of Dopegit is 2 g. When combined therapy with other hypotensive drugs, the maximum daily dose of Dopegit should not exceed 500 mg.

The dose of the drug is gradually reduced after achieving a stable hypotensive effect to the level of the minimum effective dose.

In patients with impaired renal function it is recommended to reduce the single dose of the drug. The initial daily dosage of Dopegit for children is 10 mg/kg divided into 2-4 doses. The maximum daily dosage of Dopegit for children should not exceed 65 mg/kg.

In elderly patients, a starting dosage of 125 mg once or twice daily is recommended. The maximum daily dose for elderly patients is 2 g divided into 2 doses.

Interaction

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

Combination with tricyclic antidepressants may decrease the hypotensive effect of the drug and provoke headaches, tachycardia, and agitation.

Combined use with levodopa may lead to increased antiparkinsonian effect, which is due to inhibition of peripheral decarboxylation of levodopa by methyldopa and increased concentration of levodopa in the central nervous system. In cases where inhibition of decarboxylation in the CNS is predominant, there is a decrease in the antiparkinsonian effect of levodopa.

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

Combination of Dopegit with haloperidol leads to increased likelihood of dementia, combination with digoxin in elderly patients may lead to increased likelihood of SSRIs.

To increase the hypotensive effect of the drug it is reasonable to combine it with diuretics, hydralazine and nifedipine.
Simultaneous use of the drug with β-adrenoblockers may lead to orthostatic hypotension.

The concomitant 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) increases the hypotensive effect of the drug.

The alkalization of urine during therapy with methyldopa leads to enhancement of its action, acidification of urine leads to reduction of its action.
The drug administration should be stopped 7-10 days prior to general anesthesia in order to avoid development of collaptoid condition.

The drugs for general anesthesia (sodium thiopental or halothane) should be administered with caution to patients taking methyldopa. The use of diethyl ether is contraindicated.

Dopagit increases hepatotoxicity of oral contraceptives and lithium salts.

The drug is incompatible with reserpine.

Caution should be exercised when combining Dopegit with quinidine, neuroleptics, acetazolamide and procainamide.

Contraindications

– acute hepatitis, cirrhosis;
– history of liver disease (against the background of methyldopa);
– concomitant therapy with MAO inhibitors;
– Depression;
– hemolytic anemia;
– acute myocardial infarction;
– pheochromocytoma;
– hypersensitivity to Dopegit.
The drug should be used with caution in patients with renal insufficiency (dose adjustment is required), diencephalic syndrome, elderly patients and children.

Side effects

When using Dopegit may cause:

– lethargy, somnolence, lethargy, facial nerve palsy, parkinsonism, paresthesia, spontaneous chorioatetoid movements, staggering when walking, dizziness, headache;
– orthostatic hypertension, peripheral edemas, bradycardia, hyperemia of the upper trunk, aggravation of heart failure, increased angina, in rare cases – pericarditis, myocarditis;
– glossalgia, dry mouth, vomiting, nausea, diarrhea, colitis, hepatotoxicity, pancreatitis, jaundice, increased liver transaminases activity;
– leukopenia, hemolytic anemia, agranulocytosis, thrombocytopenia;
– arthralgia, myalgia;
– galactorrhea, gynecomastia, hyperprolactinemia;
– decreased libido, decreased potency, amenorrhea;
fever, rash, urticaria – Fever, rash, exanthema, toxic epidermal necrolysis (Lyell’s syndrome);
– Salivary gland inflammation, nasal congestion;
– A positive direct Coombs test (when using the drug for over 6 months in a daily dosage of >1 g).

Overdose

In case of overdose of Dopegit, pronounced arterial hypotension, weakness, marked bradycardia, somnolence, tremor, lethargy, dizziness, flatulence, constipation, diarrhea, vomiting, nausea, bowel atony may occur.

The treatment of overdose: soon after ingestion – gastric lavage and induce vomiting in order to reduce the amount of the drug absorbed. It is reasonable to monitor the BCC, HR, electrolyte balance, renal, intestinal and brain functions. Sympathomimetics (epinephrine) may be administered if necessary.

Pregnancy use

The results of clinical studies showed no 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 Dopegit to pregnant women only under strict indications.