Hydrochlorothiazide - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) - 40.60 mg, microcrystalline cellulose - 15.0 mg, corn starch - 10.0 mg, povidone-K25 - 3.50 mg, magnesium stearate - 0.90 mg.

Dosage of 100 mg

Active substance: hydrochlorothiazide - 100.0 mg.

Excipients: lactose monohydrate (sugar milk) - 162.40 mg, microcrystalline cellulose - 60.0 mg, corn starch - 40.0 mg, povidone-K25 - 14.0 mg, magnesium stearate - 3.60 mg.

Description:Round flat cylindrical tablets of white or almost white color with a risk on one side and chamfers from two sides.

Pharmacotherapeutic group:Diuretics

ATX: & nbsp

C.03.A.A.03 Hydrochlorothiazide

Pharmacodynamics:Thiazide diuretic of medium strength.Reduces sodium reabsorption in the cortical segment of the Henle loop, without affecting its area passing through the medulla of the kidney, which determines a weaker diuretic effect compared to furosemide. It blocks carbonic anhydrase in the proximal part of the convoluted tubules, strengthens the excretion of potassium by the kidneys (sodium is exchanged for potassium in the distal tubules), hydrocarbonates and phosphates. Virtually does not affect the acid-base state (sodium is excreted either with chlorine or with hydrocarbonate, so with alkalosis, the excretion of hydrocarbonates increases, with acidosis - chloride). Increases the excretion of magnesium; detains in the body calcium ions and excretion of urates.

The diuretic effect develops in 1-2 hours, reaches a maximum after 4 hours, lasts 6-12 hours. The effect decreases with a decrease in the glomerular filtration rate and stops at a value of less than 30 ml / min.

In patients with diabetes insipidus has antidiuretic effect (reduces the volume of urine and increases its concentration).

Reduces blood pressure by reducing the volume of circulating blood, changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictor (adrenaline, noradrenaline) and increasing the depressor effect on the ganglion.On normal blood pressure, thiazide diuretics have no effect.

Pharmacokinetics:

Hydrochlorothiazide is incomplete, but it is quickly absorbed from the gastrointestinal tract. After oral administration of a dose of 100 mg, the maximum concentration in the blood plasma is achieved after 1.5-2.5 hours. At the maximum of diuretic activity (approximately 4 hours after administration), the concentration of hydrochlorothiazide in blood plasma is 2 μg / ml. The connection with plasma proteins is 40%. It is not metabolized by the liver.

Excreted by the kidneys: basically unaltered and about 4% of 2-amino-4-chloro-m-benzenedisulfonamida (reduced at alkaline pH of urine) - by glomerular filtration and tubular secretion of active in the proximal part of the nephron.

The half-life for patients with normal renal function is 6.4 hours, for patients with mild renal insufficiency - 11.5 hours, and for patients with creatinine clearance (CC) of less than 30 ml / min. - 20.7 h. Hydrochlorothiazide penetrates the placental barrier and is excreted into breast milk.

In the therapeutic range of doses, the average area under the "concentration-time" curve increases in direct proportion to the increase in dose, cumulation is insignificant when applied once a day.

Indications:

- arterial hypertension (in monotherapy, and in combination with other antihypertensive drugs);

- edematous syndrome of various genesis (chronic heart failure, nephrotic syndrome, premenstrual syndrome, acute glomerulonephritis, chronic renal failure, portal hypertension, treatment with corticosteroids);

- control polyuria, mainly with nephrogenic diabetes insipidus;

- prevention of stone formation in the genito-urinary tract in predisposed patients (reduction of hypercalciuria).

Contraindications:

- hypersensitivity to the components of the drug, to other derivatives of sulfonamide, other thiazide diuretics;

anuria;

- severe renal failure (CC less than 30 ml / min)

- severe hepatic impairment;

- difficultly controlled diabetes mellitus;

- Addison's disease;

- refractory hypokalemia, hyponatremia, hypercalcemia;

- age up to 3 years (for this dosage form);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Carefully:Hypokalemia, hyponatremia, hypercalcemia, ischemic heart disease,cirrhosis of the liver (risk of hypomagnesemia), elderly age, simultaneous reception of cardiac glycosides, progressive liver diseases (risk of hepatic coma), myopia, angle-closure glaucoma, diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, gout, systemic lupus erythematosus, severe coronary and cerebral sclerosis.

Pregnancy and lactation:

There is limited experience with the use of hydrochlorothiazide during pregnancy, especially in the first trimester.

Hydrochlorothiazide penetrates the placental barrier. Contraindicated use of the drug in the first trimester of pregnancy. In the second and third trimesters of pregnancy, the drug can be prescribed only in case of acute necessity, when the benefit to the mother exceeds the potential risk to the fetus and / or the child. There is a danger of fetal or neonatal jaundice, thrombocytopenia and other consequences. Hydrochlorothiazide penetrates into breast milk in small amounts; therefore, if the use of the drug during lactation is absolutely necessary, then breastfeeding should be discontinued.

Dosing and Administration:

Inside.

The dose should be selected individually. With a constant medical control, a minimally effective dose is established. Tablets should be taken after meals. In connection with the increased loss of potassium and magnesium ions during treatment (potassium content in the serum may drop below 3.0 mmol / l), there is a need for replacement of potassium and magnesium.

Adults

As an antihypertensive agent, the usual initial daily dose is 25-50 mg once, in monotherapy or in combination with other antihypertensive agents. Some patients have an initial dose of 12.5 mg (1/2 tablets of 25 mg), both in monotherapy and in combination therapy. It is necessary to apply a minimally effective dose, not exceeding 100 mg per day. If hydrochlorothiazide combined with other antihypertensive drugs, it may be necessary to reduce the dose of another drug in order to prevent an excessive decrease in blood pressure (BP).

Antihypertensive effect appears within 3-4 days, however, to achieve the optimal effect, it may take up to 3-4 weeks. After the end of treatment, the hypotensive effect persists for one week.

Ocular syndrome of various genesis. The usual initial dose for the treatment of edema is 25-100 mg once a day or once every two days. Depending on the clinical response, the dose can be reduced to 25-50 mg once a day or once every two days. In some severe cases, doses up to 200 mg per day may be required at the beginning of treatment.

With premenstrual syndrome, the usual dose is 25 mg per day and is used from the onset of symptoms before the onset of menstruation.

With nephrogenic diabetes insipidus recommended usual dose of 50-150 mg daily (in divided doses) to achieve a therapeutic effect (decrease of thirst and polyuria), further possible to reduce the dose.

For the prevention of stone formation - 50 mg 2 times a day.

Children

Doses are set based on the weight of the child's body. Children from 3 years - 1-2 mg / kg / day or 30-60 mg / m body surface 1 time per day. The total daily dose for children aged 3-12 years is 37.5-100 mg. After 3-5 days of treatment, it is recommended to take a break for 3-5 days. As maintenance therapy in this dose prescribed 2 times a week. In applying intermittent treatment with reception at 1 -3 or day for 2-3 days followed by a break decrease in efficiency is less pronounced and less frequent side effects develop.

Side effects:

The frequency of side effects is given in the following gradation: very often (more than 1/10); often (more than 1/100, less than 1/10); infrequently (more than 1/1000, less than 1/100); rarely (more than 1/10000, less than 1/1000); very rarely (less than 1/10000, including individual messages); frequency (frequency can not be calculated from available data).

Violations of the water-electrolyte balance:

Often: hypokalemia, hypomagnesemia, hypercalcemia and hypochloraemic alkalosis: dryness of the oral mucosa, thirst, arrhythmia, changes in mood or psyche, convulsions and muscle pain, nausea, vomiting, unusual fatigue or weakness; hypochloraemic alkalosis can cause hepatic encephalopathy or hepatic coma; hyponatremia (confusion, convulsions, lethargy, slowing down the process of thinking, increased fatigue, irritability, irritability, muscle cramps).

Metabolic disorders:

Often: hyperglycemia, glucosuria, hyperuricemia with the development of an attack of gout. Treatment with thiazides can reduce glucose tolerance, and latent diabetes mellitus can manifest. When using high doses, lipid concentrations in the serum can increase.

From the digestive system:

Rarely: cholecystitis, pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, constipation, anorexia, nausea, vomiting.

From the cardiovascular system:

Rarely: bradycardia, orthostatic hypotension, vasculitis.

From the nervous system and sensory organs:

Rarely: dizziness, fainting, transient blurred vision, acute myopia, acute attack of angle-closure glaucoma, headache, paresthesia.

From the hematopoiesis:

Rarely: leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.

Hypersensitivity reactions:

Rarely: urticaria, skin rash and itching, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, respiratory distress syndrome (including pneumonitis and noncardiogenic pulmonary edema), photosensitization, anaphylactic reactions up to shock.

From the musculoskeletal system:

Rarely: muscle weakness.

Other: decreased potency, impaired renal function, interstitial nephritis, exacerbation of systemic lupus erythematosus.

Overdose:

The most noticeable manifestation of an overdose with hydrochlorothiazide is the acute loss of fluid and electrolytes, expressed in the following signs and symptoms:

Cardiovascular: tachycardia, marked decrease in blood pressure, shock. Neuromuscular: weakness, confusion, dizziness and spasms of the calf muscles, paresthesia, impaired consciousness, increased fatigue.

Gastrointestinal: nausea, vomiting, thirst.

Kidney: polyuria, oliguria or anuria (due to hemoconcentration). Laboratory indicators: hypokalemia, hyponatremia, hypochloraemia, alkalosis, elevated concentration of urea nitrogen in the blood (especially in patients with renal insufficiency). Treatment: There is no specific antidote for hydrochlorothiazide overdose.

Induction of vomiting, gastric lavage can be a means of removing the drug. The absorption of the drug can be reduced by applying Activated carbon. In the event of a marked decrease in blood pressure or shock, the volume of circulating blood (BCC) and electrolytes (potassium, sodium) should be compensated.

It is necessary to control the water-electrolyte balance (especially the potassium content in the blood serum) and the kidney function until normal values are established. Assigning potassium and potassium-sparing diuretics to compensate for potassium deficiency.

Interaction:It is necessary to avoid simultaneous application of the drug with:

lithium preparations (renal clearance of lithium decreases, its toxicity increases).
anxiolytics and hypnotics - strengthening of antihypertensive action
antifungal agents - increases the risk of hypokalemia, if thiazides are used in combination with amphotericin B, the maximum plasma concentration of fluconazole is increased.
theophylline - increased risk of hypokalemia

Use with caution with the following preparations:

hypotensive drugs (their effect is potentiated, there may be a need for dose adjustment)
cardiac glycosides (hypokalemia and hypomagnesemia associated with the action of thiazide diuretics, may increase the toxicity of cardiac glycosides)
amiodarone (its use simultaneously with thiazide diuretics can lead to an increased risk of arrhythmias associated with hypokalemia)
hypoglycemic agents for ingestion and insulin (their effectiveness decreases, hyperglycemia may develop), dosage correction of hypoglycemic agents may be required.
metformin should be used with caution in connection with the risk of developing lactic acidosis against a background of kidney damage caused by hydrochlorothiazide.
glucocorticosteroids, calcitonin, ACTH (adrenocorticotronic hormone), glycyrrhizic acid (found in licorice root) (increases potassium excretion)
non-steroidal anti-inflammatory drugs (NSAIDs) (including cyclooxygenase-2 inhibitors (COX-2)) - can reduce diuretic, natriuretic and hypotensive effects of diuretics. In some patients with impaired renal function (eg, elderly patients or patients with dehydration, including those taking diuretics) receiving NSAID therapy, including COX-2 inhibitors, treatment with angiotensin II receptor antagonists or angiotensin-converting enzyme (ACE) inhibitors may cause further deterioration of kidney function, including the development of acute renal failure. These effects are reversible. The simultaneous use of these drugs should be conducted with caution in patients with impaired renal function.
Nondepolarizing muscle relaxants (their effect may be enhanced)
amantadine (clearance of amantadine can be reduced by hydrochlorothiazide, which leads to an increase in the concentration of amantadine in blood plasma and possible toxicity)
colestyramine, which reduces the absorption of hydrochlorothiazide.
ethanol, barbiturates and general anesthetic agents that enhance the effect of orthostatic hypotension.
Presoramiami amines (for example, epinephrine (adrenalin), norepinephrine (norepinephrine)) - decreased response to the reception of pressor amines.
Calcium salts, vitamin D - the risk of hypercalcemia.
Drugs used to treat gout (probenecid, sulfinpyrazone and allopurinol): it may be necessary to adjust the dose of uricosuric drugs, since hydrochlorothiazide can cause an increase in the concentration of uric acid in the serum. Thiazide diuretics can increase the incidence of hypersensitivity reactions by allopurinol.
Anticholinergic drugs (eg, atropine, biperidene): increase the bioavailability of thiazide diuretics by reducing the motility of the gastrointestinal tract.
Cytostatic drugs, for example, cyclophosphamide, methotrexate: the myelo-suppressing effect increases due to slowing of excretion from the body.
Methyldopa: individual cases of hemolytic anemia are described with simultaneous application.
Simultaneous use of cyclosporine increases the risk of hyperuricemia and exacerbation of gout.
Cardiac glycosides: hypokalemia and hypomagnesemia caused by the use of thiazide diuretics, increase the risk of arrhythmias in the treatment of cardiac glycosides.

Interaction of the preparation / laboratory tests

- Thiazides can reduce the concentration of iodine bound to proteins in blood plasma.

- Before carrying out studies to evaluate the function of parathyroid glands, thiazides should be discarded.

- The concentration of bilirubin in the serum can be increased.

- It is recommended to periodically monitor the potassium content in the blood serum and ECG with simultaneous use with cardiac glycosides and drugs that extend the QT interval (risk of ventricular pirouette tachycardia):

- I A class of antiarrhythmic drugs (for example, quinidine, disopyramide);

- III class of antiarrhythmic agents (for example, amiodarone, dofetilide) and sotalol;

- Some antipsychotics (for example, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, sulpiride, amisulpride, tiapride, haloperidol, droperidol);

- other medicinal products (for example, cisapride, diphemanyl methyl sulfate, erythromycin for intravenous administration, halofantrine, ketaxerine, misolastine, sparfloxacin, terfenadine, wincamine for intravenous administration).

- Carbamazepine: the risk of developing symptomatic hyponatremia.

Special instructions:

With prolonged course treatment, it is necessary to carefully monitor the clinical symptoms of water-electrolyte balance disorders, primarily in patients at high risk: patients with cardiovascular disease and impaired liver function; in case of prolonged vomiting or when signs of disturbance of the water-electrolyte balance appear, such as dryness of the oral mucosa, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, complaints from the gastrointestinal tract.

Hypokalemia can be avoided by the use of potassium-containing drugs or foods rich in potassium (fruits, vegetables), especially in the case of increased loss of potassium (increased diuresis, prolonged treatment) or simultaneous treatment with cardiac glycosides or corticosteroid drugs.

It is shown that thiazides increase the excretion of magnesium by the kidneys; this can lead to hypomagnesemia.

With reduced renal function, periodic monitoring of creatinine clearance is necessary. In patients with impaired renal function, the drug can cause azotemia, as well as cumulate. If the violation of kidney function is obvious, when oliguria comes, you should cancel the drug.

Patients with hepatic insufficiency of mild or moderate severity or with progressive liver diseases should be cautioned with thiazides, since a small change in the water-electrolyte balance and accumulation of ammonium in the blood serum can cause hepatic coma.

In the case of severe cerebral and coronary sclerosis, the administration of the drug requires special care.

Treatment with thiazide diuretics can impair glucose tolerance.During a long course of treatment with a manifest and latent diabetes mellitus, systematic control of carbohydrate metabolism is necessary; there may be a need for correction of the dose of hypoglycemic drugs.

There is evidence that thiazide diuretics, incl. hydrochlorothiazide, can cause exacerbation of systemic lupus erythematosus or lupus-like reactions. It requires increased monitoring of patients with impaired uric acid metabolism.

Thiazide diuretics can reduce the excretion of calcium by the kidneys and lead to a transient, moderate increase in serum calcium blood in the absence of an established violation of calcium metabolism. Expressed hypercalcemia may be evidence of the patient's existing hyperparathyroidism. Admission of thiazide diuretics should be discontinued before studies of the function of the parathyroid glands.

Thiazides can reduce the amount of iodine that binds to serum proteins without showing signs of thyroid dysfunction.

There is information about cases of development of photosensitivity reactions when taking thiazide diuretics.If the photosensitivity reaction occurs during treatment, it is recommended to suspend treatment. If it is decided that the diuretic should be resumed, it is necessary to protect areas of the body that can be exposed to sunlight or ultraviolet rays of type A and avoid sun exposure.

Hydrochlorothiazide can increase the concentration of cholesterol and triglycerides in the blood plasma.

In patients receiving thiazide diuretics, hypersensitivity reactions can be observed even in the absence of an anamnesis indicating the presence of allergic reactions or bronchial asthma. There are reports of the development of exacerbation or progression of systemic lupus erythematosus against the background of the use of thiazide diuretics.

During therapy, the drug is not recommended to drink alcohol. Hydrochlorothiazide can give a positive result in the conduct of doping control.

Hydrochlorothiazide can cause an idiosyncratic reaction leading to the development of acute myopia and an acute attack of secondary closed-angle glaucoma. Symptoms include: sudden reduction in visual acuity or eye pain, which usually occur within a few hours or weeks of initiating hydrochlorothiazide therapy.In the absence of treatment, acute closed-angle glaucoma can lead to a permanent loss of vision. Treatment: stop hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, immediate medical treatment or surgery may be required. Risk factors for the development of acute angle-closure glaucoma are: an allergic reaction to sulfonamides or penicillin in an anamnesis.

Effect on the ability to drive transp. cf. and fur:No special clinical studies have been conducted to assess the effect of hydrochlorothiazide on the ability to drive vehicles and work with machinery. It should be borne in mind the possibility of drowsiness and dizziness, so care must be taken when carrying out work requiring attention and driving, especially at the beginning of treatment, with an increase in the dose of the drug.

Form release / dosage:

Tablets 25 mg and 100 mg.

Packaging:

For 10, 20 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10, 20, 30, 40, 50, 60 or 100 tablets in cans of polyethylene terephthalate.

One jar or 1, 2, 3, 4, 5, 6 or 10 contour squares, together with the instructions for use, are placed in a cardboard package (bundle).

Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002767

Date of registration:17.12.2014

Expiration Date:17.12.2019

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp16.04.2017

Illustrated instructions

Instructions

Hydrochlorothiazide (Hydrochlorothiazide)