Hypothiazid^® (Tablets) Instructions for Use

ATC Code

C03AA03 (Hydrochlorothiazide)

Active Substance

Hydrochlorothiazide

Clinical-Pharmacological Group

Diuretic

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

Thiazide diuretic. It impairs the reabsorption of sodium, chloride, and water ions in the distal tubules of the nephron. It increases the excretion of potassium, magnesium, and bicarbonate ions; it retains calcium ions in the body.

The diuretic effect begins within 2 hours, reaches its maximum in 4 hours, and lasts up to 12 hours. It helps to reduce elevated blood pressure.

Furthermore, 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.

Pharmacokinetics

After oral administration, 60-80% of the dose is absorbed from the gastrointestinal tract. The time to reach C_max in plasma is 1.5-3 hours. Hydrochlorothiazide accumulates in erythrocytes.

During the elimination phase, its concentration in erythrocytes is 3-9 times higher than in plasma. Plasma protein binding is 40-70%. The V_d in the terminal elimination phase is 3-6 L/kg (which is 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-N-benzenesulfonamide.

The elimination of hydrochlorothiazide from plasma is biphasic: the T_1/2 in the initial phase is 2 hours, and in the terminal phase, it is about 10 hours.

In patients with normal renal function, elimination occurs almost exclusively by the kidneys. Overall, 50-75% of the orally administered dose is excreted unchanged in the urine.

In elderly patients and in patients with impaired renal function, the clearance of hydrochlorothiazide is significantly reduced, leading to a significant increase in its plasma concentration.

The reduced clearance observed in elderly patients is likely associated with deteriorating renal function. In patients with liver cirrhosis, no changes in the pharmacokinetics of hydrochlorothiazide are noted.

Indications

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, corticosteroid treatment), reduction of symptomatic polyuria in diabetes insipidus, glaucoma (subcompensated forms), prevention of calcium-phosphate stone formation in the urinary tract in hypercalciuria.

ICD codes

Dosage Regimen

Take orally, once daily, preferably in the morning with meals.

For arterial hypertension in adults, initiate therapy with 12.5 mg to 25 mg once daily. Titrate the dose based on therapeutic response; the maximum daily dose is 100 mg.

For edematous syndrome in adults, the initial dose is 25 mg to 100 mg daily. After the edema subsides, transition to a maintenance dose of 25 mg to 50 mg daily, or use an intermittent regimen.

For diabetes insipidus, the usual adult dose is 50 mg to 100 mg per day.

For children over 3 years of age, calculate the dose at 1 mg to 2 mg per kg of body weight per day, or 30 mg to 60 mg per m² of body surface area per day. Administer as a single daily dose. The maximum daily dose for children should not exceed 100 mg.

In elderly patients and patients with renal impairment, initiate therapy at the lower end of the dosage range due to a potentially reduced clearance of the drug. Monitor renal function and electrolyte levels closely.

For patients with impaired liver function, use with caution and monitor for signs of fluid and electrolyte imbalance.

When discontinuing long-term therapy, taper the dose gradually to avoid rebound effects.

Regularly monitor blood pressure, serum electrolytes (particularly potassium and sodium), blood glucose, and uric acid levels during treatment.

Adverse Reactions

From the digestive system nausea, vomiting, diarrhea; rarely – pancreatitis.

From the cardiovascular system orthostatic hypotension, tachycardia.

From metabolism hypokalemia, hypomagnesemia, hyponatremia, hypochloremic alkalosis, hyperuricemia, hypercalcemia.

From the endocrine system hyperglycemia.

From the hematopoietic system rarely – neutropenia, thrombocytopenia.

From the organ of vision rarely – visual disturbances.

From the nervous system weakness, fatigue, dizziness, paresthesia.

Allergic reactions rarely – allergic dermatitis.

From the skin and subcutaneous tissues non-melanoma skin cancer (based on available data from epidemiological studies, a cumulative dose-dependent relationship has been identified between hydrochlorothiazide and NMSC).

Contraindications

Severe renal failure, anuria, severe hepatic failure or hepatic encephalopathy (risk of hepatic coma), severe forms of gout and diabetes mellitus, refractory hypokalemia, hypercalcemia, hyponatremia, adrenal cortex insufficiency (Addison’s disease); first trimester of pregnancy, breastfeeding period; children under 3 years of age (for the solid dosage form); hypersensitivity to sulfonamides.

Use in Pregnancy and Lactation

Contraindicated in the first trimester of pregnancy and during breastfeeding.

Use with caution in the second and third trimesters of pregnancy.

Hydrochlorothiazide is excreted in breast milk.

Use in Hepatic Impairment

Contraindicated in severe hepatic failure or hepatic encephalopathy (risk of hepatic coma).

Use in Renal Impairment

Contraindicated in severe renal failure, anuria.

Pediatric Use

Contraindicated in children under 3 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Use with caution in patients with gout and diabetes mellitus, with prolongation of the QT interval on ECG, with concurrent use of drugs that can cause polymorphic ventricular tachycardia of the “torsades de pointes” type or prolong the QT interval on ECG; concurrently with lithium preparations, drugs capable of causing hypokalemia, with cardiac glycosides; with a history of allergic reactions to penicillin; with systemic lupus erythematosus; with coronary artery 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 second and third trimesters of pregnancy; in children from 3 to 18 years of age.

In patients with renal failure, systematic monitoring of plasma electrolyte concentrations and creatinine clearance is necessary.

If signs of potassium deficiency appear, as well as with the simultaneous use of cardiac glycosides, corticosteroids, and ACTH, the administration of potassium preparations or potassium-sparing diuretics is indicated.

With long-term use, a diet rich in potassium should be followed.

Concomitant use of diuretics with NSAIDs is not recommended.

Drug Interactions

With simultaneous use of antihypertensive agents, non-depolarizing muscle relaxants, their action is enhanced.

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

With simultaneous use with corticosteroids, 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.

Marked 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 cannot be excluded.

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

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

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

With simultaneous use with digoxin, an increased risk of glycoside intoxication is possible.

With simultaneous use with indomethacin, piroxicam, naproxen, phenylbutazone, some reduction 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, the absorption and diuretic effect of hydrochlorothiazide are reduced.

With simultaneous use with lithium carbonate, an increase in the blood concentration of lithium salts to a toxic level is possible.

With simultaneous use with orlistat, the effectiveness of hydrochlorothiazide is reduced, 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 torsades de pointes ventricular arrhythmia are possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.