Hydrochlorthiazide, tablets 100 mg, 20 pcs.

Hydrochlorthiazide is a thiazide diuretic. Disrupts reabsorption of sodium, chlorine and water ions in the distal tubules of the nephron. Increases excretion of potassium, magnesium, bicarbonate ions; delays calcium ions in the body. Diuretic effect comes in 2 hours, reaches a maximum in 4 hours and lasts up to 12 hours. Helps to reduce high blood pressure. In addition, it reduces polyuria in patients with diabetes mellitus (the mechanism of action is not fully understood). In some cases it lowers the intraocular pressure in glaucoma.

Pharmacokinetics

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 excretion phase its concentration in erythrocytes is 3-9 times higher than in plasma. Binding to plasma proteins is 40-70%. Vd in the terminal phase of excretion is 3-6 l/kg (equivalent to 210-420 l at a body weight of 70 kg).

Hydrochlorothiazide is metabolized to a very small extent. Its only metabolite detected in trace amounts is 2-amino-4-chloro-M-benzenedisulfonamide.

In elderly patients and in patients with impaired renal function the clearance of hydrochlorothiazide is significantly reduced, which leads to a significant increase in its plasma concentration. The decrease in clearance observed in elderly patients appears to be associated with impaired renal function. In patients with liver cirrhosis no changes in pharmacokinetics of hydrochlorothiazide have been noted.

Indications

Arterial hypertension (monotherapy or in combination with other antihypertensive drugs), edematous syndrome of various origins (chronic heart failure, nephrotic syndrome, premenstrual syndrome, acute glomerulonephritis, chronic renal failure, portal hypertension, treatment with corticosteroids), control of polyuria (mainly in nephrogenic diabetes insipidus), prevention of stone formation in the genitourinary tract in predisposed patients (reduction of hypercalciuria).

Pharmacological effect

Hydrochlorothiazide is a thiazide diuretic. It interferes with 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. Helps reduce high blood pressure. In addition, it reduces polyuria in patients with diabetes insipidus (the mechanism of action has not been fully elucidated). In some cases, it lowers intraocular pressure in glaucoma.

Pharmacokinetics

After oral administration, 60-80% of the dose is absorbed from the gastrointestinal tract. The time to reach Cmax in plasma is 1.5-3 hours. Hydrochlorothiazide accumulates in red blood cells. 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 elimination phase is 3-6 l/kg (equivalent to 210-420 l for 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-benzene disulfonamide.

The elimination of hydrochlorothiazide from plasma has a two-phase character: T1/2 in the initial phase is 2 hours, in the terminal phase – about 10 hours. In patients with normal renal function, elimination is carried out almost exclusively by the kidneys. In general, 50-75% of an oral dose is excreted unchanged in the urine.

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 worsening renal function. In patients with liver cirrhosis, no changes in the pharmacokinetics of hydrochlorothiazide are observed.

Active ingredient

Hydrochlorothiazide

Composition

Active ingredient:

hydrochlorothiazide (in terms of 100% substance) – 25 mg or 100 mg;

Excipients:

microcrystalline cellulose,

milk sugar (lactose),

potato starch,

magnesium stearate

Contraindications

Hypersensitivity (including to other sulfonamides), anuria, severe renal (Clcreatinine – less than 30 ml/min) or liver failure, difficult-to-control diabetes mellitus, Addison’s disease, gout, children’s age (up to 3 years).

Side Effects

Hypokalemia, hypomagnesemia, hypercalcemia and hypochloremic alkalosis: dry mouth, thirst, irregular heart rhythm, mood or mental changes, cramps and muscle pain, nausea, vomiting, unusual tiredness or weakness. Hypochloremic alkalosis can cause hepatic encephalopathy or hepatic coma.

Hyponatremia: confusion, convulsions, lethargy, slow thinking, fatigue, excitability, muscle cramps.

Metabolic phenomena: hyperglycemia, glucosuria, hyperuricemia with the development of an attack of gout. Treatment with thiazides may reduce glucose tolerance, and latent diabetes mellitus may become manifest. When using high doses, serum lipid levels may increase.

From the gastrointestinal tract: cholecystitis or pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, constipation, anorexia.

From the cardiovascular system and blood (hematopoiesis, hemostasis): arrhythmias, orthostatic hypotension, vasculitis; very rarely – leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.

From the nervous system and sensory organs: dizziness, blurred vision (temporarily), headache, paresthesia.

Hypersensitivity reactions: urticaria, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, respiratory distress syndrome (including pneumonitis and non-cardiogenic pulmonary edema), photosensitivity, anaphylactic reactions up to shock.

Other: decreased potency, impaired renal function, interstitial nephritis.

Interaction

With the simultaneous use of antihypertensive drugs and non-depolarizing muscle relaxants, their effect is enhanced.

With the simultaneous use of barbiturates, diazepam, ethanol, the risk of developing orthostatic hypotension increases.

When used simultaneously with GCS, there is a risk of developing hypokalemia, as well as orthostatic hypotension.

When used simultaneously 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 kidney dysfunction increases. The development of hypokalemia cannot be excluded.

With the simultaneous use of oral hypoglycemic drugs, their effectiveness decreases.

With the simultaneous use of calcium and/or vitamin D supplements in high doses, hypercalcemia and the risk of developing metabolic acidosis are possible due to slower excretion of calcium in the urine under the influence of thiazide diuretics.

When used simultaneously with allopurinol, the risk of allergic reactions increases, especially in patients with impaired renal function.

When used simultaneously with digoxin, the risk of developing glycoside intoxication may increase.

When used simultaneously with indomethacin, piroxicam, naproxen, phenylbutazone, the hypotensive effect may be slightly reduced.

When used simultaneously with irbesartan, an additive hypotensive effect may develop.

When used simultaneously with carbamazepine, there are reports of the development of hyponatremia.

When used simultaneously with colestipol and cholestyramine, the absorption and diuretic effect of hydrochlorothiazide decreases.

When used simultaneously with lithium carbonate, the concentration of lithium salts in the blood may increase to a toxic level.

When used simultaneously with orlistat, the effectiveness of hydrochlorothiazide decreases, which can lead to a significant increase in blood pressure and the development of a hypertensive crisis.

When used simultaneously with sotalol, hypokalemia and the development of ventricular arrhythmia of the “pirouette” type are possible.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 °C

Shelf life

2 years

Manufacturer

Valenta Pharm JSC, Russia