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 hypotensive agents), edema syndrome of different genesis (chronic heart failure, nephrotic syndrome, premenstrual syndrome, acute glomerulonephritis, chronic renal failure, portal hypertension, treatment with corticosteroids), control of polyuria (mainly in nephrogenic nonsanguineous diabetes), prevention of urogenital calculi formation in predisposed patients (reduction of hypercalciuria).

Active ingredient

Composition

Active substance:

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

Auxiliary substances:

Microcrystalline cellulose,

Milk sugar (lactose),

Potato starch,

Magnesium stearate

How to take, the dosage

Ingestion, after meals. The dosage of the drug is set individually. With constant medical supervision the minimum effective dose is established.

Adults

As an antihypertensive agent: The usual starting daily dose of the drug is 25-50 mg once, as monotherapy or in combination with other antihypertensive agents. For some patients a starting dose of 12.5 mg, either as monotherapy or in combination, may be sufficient. A minimum effective dose not exceeding 100 mg per day should be used.

If hydrochlorothiazide is combined with other hypotensive drugs, it may be necessary to reduce the dose of the other drug to prevent excessive reduction of blood pressure. Hypotensive effect occurs in 3-4 days, but it may take 3-4 weeks to achieve optimal therapeutic effect.
After discontinuation of treatment, the hypotensive effect is maintained for one week.

Oedematous syndrome of various etiology: Usual initial daily dose is 25-100 mg once daily or once every other day. Depending on the therapeutic effect the dose may be reduced to 25-50 mg once a day or once every two days. In some severe cases, doses up to 200 mg daily may be required at the beginning of treatment.

Premenstrual syndrome: the usual dose is 25 mg daily and is used from the onset of symptoms until the onset of menstruation.

Nephrogenic non-sugar diabetes: the usual daily dose is 50-150 mg in several doses.

Children

The doses are set based on the child’s body weight. The usual pediatric daily dose is 1-2 mg/kg body weight or 30-60 mg per square meter of body surface area, prescribed once a day. The total daily dose for children under 2 years of age is 12.5 to 37.5 mg; ages 2 to 12 years, 37.5 to 100 mg.

Interaction

When concomitant use of antihypertensives, nondepolarizing myorelaxants, their effect is increased.

Concomitant use of barbiturates, diazepam, ethanol increases the risk of orthostatic hypotension.

Simultaneous use with GCS increases the risk of hypokalemia and orthostatic hypotension.

Concomitant use with ACE inhibitors (including captopril, enalapril) increases the antihypertensive effect.

Perhaps severe arterial hypotension, especially after the first dose of hydrochlorothiazide, apparently due to hypovolemia, which leads to transient enhancement of hypotensive effect of ACE inhibitor.

The risk of impaired renal function increases. The development of hypokalemia is not excluded.

The concomitant use of oral hypoglycemic agents decreases their effectiveness.

In concomitant use of calcium and/or vitamin D preparations in high doses hypercalcemia and risk of metabolic acidosis due to delayed urinary calcium excretion caused by thiazide diuretics are possible.

Concomitant use with allopurinol increases the risk of allergic reactions, especially in patients with impaired renal function.

Concomitant use with digoxin may increase the risk of glycoside intoxication.

Concomitant use with indomethacin, piroxicam, naproxen, phenylbutazone may slightly reduce the hypotensive effect.

Concomitant use with irbesartan may result in additive hypotensive effect.

In concomitant use with carbamazepine there have been reports of hyponatremia.

Concomitant use with colestipol, colestiramine decreases absorption and diuretic effect of hydrochlorothiazide.

Concomitant use with lithium carbonate may increase the blood concentration of lithium salts to toxic levels.

Concomitant use with orlistat decreases the effectiveness of hydrochlorothiazide, which may lead to a significant increase in BP and development of hypertensive crisis.

Concomitant use with sotalol may cause hypokalemia and development of pirouette-type ventricular arrhythmias.

Contraindications

Hypersensitivity (including to other sulfonamides), anuria, severe renal (Scl is less than 30 ml/min) or hepatic insufficiency, diabetes that is difficult to control, Addison’s disease, gout, childhood age (under 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 fatigue or weakness. Hypochloremic alkalosis can cause hepatic encephalopathy or hepatic coma.

Hyponatremia: confusion, convulsions, lethargy, slowed thinking process, fatigue, agitation, muscle cramps.

Metabolic phenomena: hyperglycemia, glucosuria, hyperuricemia with the development of a gout attack. Treatment with thiazides may decrease glucose tolerance, and latent diabetes mellitus may manifest. Serum lipid levels may increase with high doses.

Gastrointestinal disorders: cholecystitis or pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, constipation, anorexia.

Cardiovascular system and blood (hemopoiesis, hemostasis): arrhythmia, orthostatic hypotension, vasculitis; very rarely – leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.

Nervous system and sensory system disorders: dizziness, blurred vision (temporarily), headache, paresthesias.

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

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

Similarities