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Pharmacological action of Esidrex
Thiazide diuretic. Violates the reabsorption of sodium, chlorine and water ions in the distal tubules of the nephron. Increases the excretion of potassium, magnesium, bicarbonate ions; retains calcium ions in the body. The diuretic effect occurs after 2 hours, reaches a maximum after 4 hours and lasts up to 12 hours. It helps to reduce high blood pressure. In addition, it reduces polyuria in patients with diabetes insipidus (the mechanism of action is not fully understood). In some cases, it lowers intraocular pressure in glaucoma.
After oral administration, 60-80% of the dose is absorbed from the gastrointestinal tract. Time to reach Cmax in plasma is 1.5-3 hours. Hydrochlorothiazide accumulates in erythrocytes. In the elimination phase, its concentration in erythrocytes is 3-9 times higher than in plasma. Plasma protein binding - 40-70%. Vd in the terminal phase of excretion is 3-6 l / kg (which is equivalent to 210-420 l with a body weight of 70 kg).
Hydrochlorothiazide is metabolized to a very small extent. Its only metabolite found in trace amounts is 2-amino-4-chloro-M-benzenedisulfonamide.
Excretion of hydrochlorothiazide from plasma is biphasic: T1/2 in the initial phase is 2 hours, in the terminal phase - about 10 hours. In patients with normal renal function, excretion is carried out almost exclusively by the kidneys. In general, 50-75% of the dose taken orally is excreted in the urine unchanged.
In elderly patients and with impaired renal function, the clearance of hydrochlorothiazide is significantly reduced, which leads to a significant increase in its concentration in the blood plasma. The decrease in clearance observed in elderly patients appears to be associated with impaired renal function. In patients with cirrhosis of the liver, changes in the pharmacokinetics of hydrochlorothiazide are not observed.
Indications of the active substances of the drug Hydrochlorothiazide
Arterial hypertension (as monotherapy or as part of combination therapy), edematous syndrome of various origins (chronic heart failure, nephrotic syndrome, premenstrual syndrome, acute glomerulonephritis, chronic renal failure, portal hypertension, fluid retention in obesity, treatment of corticosteroids ), reduction of symptomatic polyuria in diabetes insipidus, glaucoma (subcompensated forms), prevention of the formation of calcium phosphate calculi in the urinary tract with hypercalciuria.
Dosage regimen of Esidrex
Is taken orally. The scheme of application depends on the indications, clinical situation, concomitant diseases.
For adults, a single dose is 12.5-100 mg 1 time / day.
For children over 3 years of age, the dose is 1-2 mg / kg / day or 30-60 mg / m2of body surface 1 time / day.
Contraindications for use
Severe renal failure, anuria, severe hepatic failure or hepatic encephalopathy (risk of developing hepatic coma), severe forms of gout and diabetes mellitus, refractory hypokalemia, hypercalcemia, hyponatremia, adrenal insufficiency (Addison's disease); I trimester of pregnancy, breastfeeding period; children under 3 years of age (for solid dosage form); hypersensitivity to sulfonamides.
Application during pregnancy and lactation breastfeeding is
Use in the first trimester of pregnancy and during contraindicated.
Use with caution in the II and III trimesters of pregnancy.
Hydrochlorothiazide is excreted in breast milk.
Application for violations of liver function
Use is contraindicated in severe hepatic failure or hepatic encephalopathy (risk of developing hepatic coma).
Application for impaired renal function
Use is contraindicated in severe renal failure, anuria.
Use in children
Use in children under 3 years of age is contraindicated.
Use in elderly patients
Use with caution in elderly patients.
Use with caution in patients with gout and diabetes mellitus, with an increase in the duration of the QT interval on the ECG, while being used with drugs that can cause polymorphic ventricular tachycardia of the "pirouette" type or increase the duration of the QT interval on the ECG; simultaneously with lithium preparations, which can cause hypokalemia, with cardiac glycosides; with a history of allergic reactions to penicillin; with systemic lupus erythematosus; with ischemic heart disease, severe atherosclerosis of the coronary or cerebral arteries, chronic heart failure; with a history of non-melanoma skin cancer; in elderly patients; in the II and III trimesters of pregnancy; in children from 3 to 18 years old.
In patients with renal insufficiency, systematic monitoring of plasma concentrations of electrolytes and CC is necessary.
When signs of potassium deficiency appear, as well as with the simultaneous use of cardiac glycosides, GCS and ACTH, the appointment of potassium preparations or potassium-sparing diuretics is indicated.
With long-term use, you should follow a diet rich in potassium.
The simultaneous use of diuretics with NSAIDs is not recommended.
With the simultaneous use of antihypertensive drugs, non-depolarizing muscle relaxants, their effect is enhanced.
With the simultaneous use of barbiturates, diazepam, ethanol, the risk of orthostatic hypotension increases.
With simultaneous use with GCS, there is a risk of hypokalemia, as well as orthostatic hypotension.
With simultaneous use with ACE inhibitors (including captopril, enalapril), the antihypertensive effect is enhanced.
Severe arterial hypotension is possible, especially after taking the first dose of hydrochlorothiazide, apparently due to hypovolemia, which leads to a transient increase in the hypotensive effect of the ACE inhibitor.
The risk of impaired renal function increases. The development of hypokalemia is not excluded.
With the simultaneous use of oral hypoglycemic drugs, their effectiveness decreases.
With the simultaneous use of calcium and / or vitamin D preparations in high doses, hypercalcemia and the risk of developing metabolic acidosis due to a slowdown in the excretion of calcium in the urine under the influence of thiazide diuretics are possible.
When used simultaneously with allopurinol, the risk of allergic reactions increases, especially in patients with impaired renal function.
With simultaneous use with digoxin, an increase in the risk of developing glycosidic intoxication is possible.
With simultaneous use with indomethacin, piroxicam, naproxen, phenylbutazone, a slight decrease in the hypotensive effect is possible.
With simultaneous use with irbesartan, the development of an additive hypotensive effect is possible.
With simultaneous use with carbamazepine, there are reports of the development of hyponatremia.
With simultaneous use with colestipol, cholestyramine, absorption and diuretic effect of hydrochlorothiazide decreases.
With simultaneous use with lithium carbonate, it is possible to increase the concentration of lithium salts in the blood to a toxic level.
With simultaneous use with orlistat, the effectiveness of hydrochlorothiazide decreases, which can lead to a significant increase in blood pressure and the development of a hypertensive crisis.
With simultaneous use with sotalol, hypokalemia and the development of ventricular arrhythmias of the "pirouette" type are possible.
From the digestive system: nausea, vomiting, diarrhea; rarely - pancreatitis.
From the side of the cardiovascular system: orthostatic hypotension, tachycardia.
From the side of metabolism: hypokalemia, hypomagnesemia, hyponatremia, hypochloremic alkalosis, hyperuricemia, hypercalcemia.
From the endocrine system: hyperglycemia.
From the hematopoietic system: rarely - neutropenia, thrombocytopenia.
From the side of the organ of vision: rarely - visual impairment.
From the side of the central nervous system and peripheral nervous system: weakness, fatigue, dizziness, paresthesia.
Allergic reactions: rarely - allergic dermatitis.