How long does it take for hypothiazide to start working? Reviews for hypothiazide. Pharmacokinetics of a special category of patients

Hypothiazide is a popular drug used by hypertensive patients to quickly reduce blood pressure. But a lasting effect from treatment can be achieved by following the doctor’s recommendations and following a diet.

The diuretic hypothiazide is a drug that is deservedly popular among doctors and patients. This is a Hungarian drug from the group of benzodiazepines with a fairly powerful diuretic effect. The main active ingredient is similar to the trade name - hydrochlorothiazide.

The diuretic is available only in tablet form, so it is easy to use for edema syndrome without medical advice. But independent attempts to treat severe heart and kidney pathologies, as well as some eye diseases, with hydrochlorothiazide can cause irreparable harm to health.

It is important to follow medical recommendations, dosage regimen and dosage to avoid negative consequences. Before the first appointment, a medical consultation is required. The occurrence of side effects that cannot be excluded (especially with long-term use) should also be reported to your doctor.

Features of pharmacokinetics and pharmacodynamics

Hydrochlorothiazide directly affects the electrolyte balance, reducing the severity of edema syndrome. The diuretic increases the volume of diuresis by blocking the reabsorption of chlorine and sodium inside the initial part of the renal tubules. As a result, the release and subsequent removal of all other ions, namely magnesium and potassium, is enhanced.

Due to a decrease in circulating blood volume, the total peripheral vascular resistance decreases - high blood pressure decreases. An important difference between hypothiazide is that this drug does not have any significant effect on normal blood pressure levels.

Hypothiazide, when taken orally (not sublingually, that is, not under the tongue), is absorbed into the blood relatively quickly, but not completely. A small part of the drug passes through the digestive tract transiently. The initial effect of increasing diuresis is observed after 120 minutes (about 2 hours), the achievement of maximum effectiveness is observed after 4 hours from the moment of taking the tablet. The binding rate of the active substance to blood proteins is 40%. The half-life of the drug is about 6-7 hours, that is, the total duration of the diuretic effect is 12 hours.

Hydrochlorothiazide is excreted mainly through the urinary tract, that is, with urine in an almost unchanged form.

As in many other cases, the rate of excretion of hydrochlorothiazide is determined by the functional abilities of the kidneys. If the excretory function of both kidneys is not impaired, then hypothiazide is excreted within the specified period of time. If the concentration and other abilities of the kidneys are reduced, then the rate of excretion decreases. In some patients it may decrease by 2 times.

The active substance hypothiazide is allowed for pregnant women only if the expected positive effect outweighs the possible risks. This drug easily penetrates the placental barrier. In addition, the speed of blood flow inside the placenta itself slows down, and the risk of developing hemorrhagic syndrome and hemolytic disease increases for the fetus.

The same recommendations apply to women who are breastfeeding. The pharmaceutical drug penetrates into breast milk in fairly high concentrations. Only if the use of the medicine is very necessary, can it be recommended to a nursing mother. But when prescribing the drug, the doctor must warn that during hypothiazide therapy, natural feeding of the child should be stopped.

Caution must be exercised when using hypothiazide in combination with certain other drugs, as drug interactions are possible. This risk is most relevant when combining hydrochlorothiazide and

• alcohol, narcotic analgesics and barbiturates - the likelihood of orthostatic collapse increases;
• amantadine due to increased toxicity;
• muscle relaxants due to increased influence;
• NSAIDs, as the diuretic effect decreases;
• corticosteroids due to decreased potassium concentrations;
• antidiabetic drugs, as they can provoke hyperglycemia;
• glycosides of the cardiac group due to increased toxicity;
• other antihypertensive drugs due to mutual enhancement of the main effect.

The active substance hypothiazide can affect glucose tolerance, uric acid metabolism, and parathyroid function. Only a doctor can evaluate all the nuances of using hypothiazide, so independent treatment with this diuretic is undesirable.

Indications for use

The required dosage of hypothiazide is selected individually for a particular patient. More often this drug is used for the following conditions:

• initial stage of urolithiasis (with small stone size);
• edema syndrome of various origins;
• arterial hypertension (as monotherapy or in combination with other drugs);
• premenstrual syndrome;
• nephrogenic diabetes insipidus;
• gestosis in pregnant women (if other therapy is not possible).

In any situation, hypothiazide is used as a means of routine treatment and is not suitable for emergency care.

Contraindications for use

Hypothiazide diuretic tablets can be harmful. This medicine is contraindicated for use in the following situations:

• hypersensitivity and/or intolerance to individual components of the drug itself or other representatives of this drug group;
• pregnancy at gestational age 1-12 weeks;
• Addison-Beermer disease;
• pronounced disturbances in water and electrolyte balance (significant decrease in the concentration of potassium, calcium, sodium);
• decompensated diabetes mellitus;
• significant impairment of the functional abilities of the renal and/or liver tissue;
• state of anuria;
• lactation period (you need to stop breastfeeding).

Some conditions are relative contraindications. The use of hypothiazide is permitted if other treatment options are impossible and a significant positive result is expected.

How to take hypothiazide

Instructions for use of the drug indicate that its traditional dosage varies from 25 to 100 mg per day. The drug is taken daily or every other day. As the active substance accumulates, the dose is reduced.

The full diuretic effect of the drug appears after 3-4 days. In some patients, the maximum effect is observed only after 3-4 weeks of regular use, sometimes it occurs earlier. After discontinuation of the drug, its hypotensive effect persists for another 6-7 days.

The tablets are taken in the morning after eating any food. In order not to get into an awkward situation, you need to remember that the primary effect of hypothiazide will occur within a few hours. The amount of urine increases significantly, so the urge to urinate may become unbearable.

The patient needs to understand that one cannot rely only on a diuretic; correction of one’s own diet and drinking regimen is required. Moderate and feasible physical activity almost always has a positive effect on the course of the disease.

A mandatory part of any treatment is dietary nutrition.

Options for prohibited and permitted foods and culinary dishes should be checked with your doctor. As a rule, it is necessary to exclude or limit fatty and fried foods, lactic acid dishes, fresh vegetables and fruits. For patients with diabetes, a special diet has been developed that takes into account the amount of carbohydrates consumed. For patients with renal and cardiac pathologies, salt restriction is a must.

The volume of fluid consumed should correspond to the patient's physical activity. Water and liquid foods should be supplied to the body in sufficient, but not excessive quantities.

Hypothiazide is a time-tested drug. It effectively eliminates edema of various origins, but self-medication is unacceptable.

1 tablet contains hydrochlorothiazide 25 mg

pharmachologic effect

Diuretic.

At maximum therapeutic doses, the diuretic/natriuretic effect of all thiazides is approximately the same. Natriuresis and diuresis occur within 2 hours and reach their maximum after about 4 hours. They also reduce carbonic anhydrase activity by increasing the excretion of bicarbonate ion, but this effect is usually mild and does not affect urine pH.

Hydrochlorothiazide also has antihypertensive properties. Thiazide diuretics have no effect on normal blood pressure.

Indications

• arterial hypertension (in the form of monotherapy, as part of complex antihypertensive therapy);
• edema syndrome of various origins (including chronic heart failure, nephrotic syndrome, premenstrual tension 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 urinary tract in predisposed patients (reduction of hypercalciuria).

Directions for use and doses

The dose should be selected individually. With constant medical supervision, the minimum effective dose is established. The drug should be taken orally after meals.

For adults

At arterial hypertension The initial dose is 25-50 mg/day once, as monotherapy or in combination with other antihypertensive drugs. For some patients, an initial dose of 12.5 mg is sufficient (either as monotherapy or in combination). It is necessary to use the minimum effective dose, not exceeding 100 mg/day. When combined Hypothiazide with other antihypertensive drugs, it may be necessary to reduce the dose of the other drug to prevent an excessive decrease in blood pressure.

The hypotensive effect appears within 3-4 days, but it may take 3-4 weeks to achieve optimal effect. After completion of therapy, the hypotensive effect persists for 1 week.

At edematous syndrome of various origins The initial dose is 25-100 mg/day once or once every 2 days. Depending on the clinical response, the dose can be reduced to 25-50 mg/day once or once every 2 days. In some severe cases, at the beginning of treatment, it may be necessary to increase the dose of the drug to 200 mg/day.

At premenstrual tension syndrome the drug is prescribed at a dose of 25 mg/day and is used from the onset of symptoms until the onset of menstruation.

At nephrogenic diabetes insipidus The usual daily dose of the drug is 50-150 mg (in several doses).

Due to increased loss of potassium and magnesium ions during treatment (serum potassium levels may be<3.0 ммоль/л) возникает необходимость в замещении калия и магния.

For children

Doses should be set based on the child’s body weight. Usual pediatric daily doses: 1-2 mg/kg body weight or 30-60 mg/m2 body surface area 1 time/day. Daily dose children aged 3 to 12 years is 37.5-100 mg.

Contraindications

• anuria;
• severe renal failure (CK<30 мл/мин);
• severe liver failure;
• difficult-to-control diabetes mellitus;
• Addison's disease;
• refractory hypokalemia, hyponatremia, hypercalcemia;
• children up to 3 years old
• hypersensitivity to the components of the drug;
• hypersensitivity to sulfonamide derivatives.

special instructions

The use of potassium-containing drugs or foods rich in potassium (including fruits, vegetables), especially when potassium is lost due to increased diuresis, prolonged diuretic therapy, or concomitant treatment with digitalis glycosides or corticosteroid drugs, helps avoid hypokalemia.

Increased magnesium excretion in urine when using thiazides can lead to hypomagnesemia.

Alcohol, barbiturates, and opioid analgesics enhance the orthostatic hypotensive effect of thiazide diuretics.

In the initial stage of using the drug (the duration of this period is determined individually), it is forbidden to drive a car or perform work that requires increased attention.

Storage conditions

The drug should be stored out of the reach of children, protected from light at a temperature of 15° to 25°C.

INN: Hydrochlorothiazide

Manufacturer: HINOIN Pharmaceutical and Chemical Products Plant CJSC

Anatomical-therapeutic-chemical classification: Hydrochlorothiazide

Registration number in the Republic of Kazakhstan: No. RK-LS-5No. 013403

Registration period: 04.02.2014 - 04.02.2019

Instructions

Tradename

Hypothiazide

International nonproprietary name

Hydrochlorothiazide

Dosage form

Tablets 25 mg, 100 mg

Compound

One tablet contains

active substance- hydrochlorothiazide 25 mg or 100 mg,

Excipients: magnesium stearate, gelatin, talc, corn starch, lactose monohydrate.

Description

Flat tablets are white or almost white, with a break mark on one side and an “H” engraving on the other side.

Pharmacotherapeutic group

Diuretics. Thiazides. Hydrochlorothiazide.

ATX code C03AA03

Pharmacological properties

Pharmacokinetics

Well absorbed after oral administration, the diuretic and natriuretic effect appears within 2 hours after administration, reaches its peak after about 4 hours and maintains its effect for 6-12 hours. Protein binding is 40%. A significant portion is excreted unchanged through the kidneys. The half-life is 6.4 hours with normal renal function, in case of mild renal impairment - 11.5 hours, in case of severe renal impairment (creatinine clearance<30 мл/мин) - 20,7 часов. Проникает через плаценту и выделяется в небольшом количестве в грудное молоко.

Pharmacodynamics

Direct inhibition of Na+ and Cl- reabsorption in the distal tubule is primarily responsible for the action of the sulfonamide derivative. As a result of this action, the release of Na+, Cl-, as well as water, then potassium and magnesium increases. The diuretic effect of hydrochlorothiazide reduces plasma volume, increases plasma renin activity and aldosterone excretion, which subsequently increases urinary excretion of potassium and bicarbonate and decreases serum potassium levels. The renin-aldosterone connection is mediated by angiotensin II, so coadministration with an angiotensin II receptor antagonist may alter potassium excretion associated with thiazide diuretics.

There is also a weak inhibitory effect on carbonic anhydrase; in this regard, the secretion of bicarbonate increases moderately without a significant change in urine pH.

Indications for use

Edema syndrome of various origins (with heart, kidney or liver diseases, premenstrual syndrome, drug-induced edema, for example, as a result of treatment with corticosteroids)

Hypertension (in mild forms of the disease as monotherapy or in combination with antihypertensive drugs)

Paradoxically, to reduce polyuria, mainly in diabetes insipidus of renal origin

To reduce hypercalciuria

Directions for use and doses

Individual dosage selection and strict medical supervision are required. Due to increased potassium and magnesium losses during treatment, potassium replacement may be required (<3.0 ммоль/л) и магния, особенно в случае сердечной недостаточности, сниженной функции печени и одновременного лечения дигиталисом. Желательно принимать препарат после еды.

Adults

For the treatment of edema: the usual initial dose is 25-100 mg of the drug once a day or as a bolus of the drug (for example, once every two days), which, depending on the effect, can be reduced to a maintenance dose of 25-50 mg.

In some severe cases, an initial dose of 200 mg may be required.

Premenstrual edema: The usual dose may be 25 mg per day from the onset of symptoms until the onset of menstruation.

As an antihypertensive agent: The usual dose is 25-100 mg per day, as a single dose, as monotherapy or in combination with other antihypertensive agents.

For some patients, an initial dose of 12.5 mg (as monotherapy or in combination with an antihypertensive drug) may be sufficient. For the desired therapeutic effect, it is necessary to use the minimum effective dose, which should not exceed 100 mg per day.

In the case of combination therapy, in order to prevent a sharp decrease in blood pressure, it is necessary to reduce the dose of one of the drugs.

The antihypertensive effect occurs after 3-4 days of taking the drug. It will take 3-4 weeks to achieve optimal effect. The antihypertensive effect continues for 1 week after the end of treatment.

For diabetes insipidus to reduce polyuria, the usual daily dose is 50-150 mg (in several doses).

For children the average daily dose is 1-2 mg/kg body weight or 30-60 mg/m² as a single dose. The general daily dose for children aged 3 to 12 years is 37.5-100 mg per day.

Side effects

The following categories are used to classify the frequency of adverse effects: very common (≥ 1/10), common (≥ 1/100 to<1/10), нечасто (≥ 1/1.000 до <1/100), редко (≥ 1/10.000 до <1/1.000), очень редко (<1/10.000), неизвестно (не может быть определено на основании имеющихся данных).

Infrequently

Respiratory distress syndrome, including pneumonia and pulmonary edema

Very rarely

Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia

Frequency unknown

Hypokalemia, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, glucosuria, hyperuricemia - in case of higher doses, an increase in blood lipid levels is possible

Arrhythmia, orthostatic hypotension - dizziness, headache, convulsions, paresthesia, confusion, lethargic sleep, nervousness, mood changes - transient visual impairment, xanthopsia - dry mouth, thirst, nausea, vomiting, inflammation of the salivary glands, constipation

Jaundice (intrahepatic cholestatic jaundice), pancreatitis, cholecystitis - renal failure, interstitial nephritis - muscle spasms and pain - hypochloremic alkalosis, which can cause hepatic encephalopathy or hepatic coma - hyperuricemia can precipitate gout attacks in asymptomatic patients - impaired glucose tolerance, which can cause manifestation of latent diabetes mellitus - anorexia, exhaustion - vasculitis, necrotizing vasculitis

Anaphylactic reaction, shock - photosensitivity, urticaria, purpura, toxic epidermal necrolysis, Steven-Johnson syndrome - sexual disorders

Contraindications

Hypersensitivity to the components of the drug and other sulfonamides

Severe renal disease (creatinine clearance< 30 мл/мин) или печеночная недостаточность

Treatment-resistant hypokalemia or hypercalcemia

Refractory hyponatremia

Symptomatic hyperuricemia (gout)

Hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption

Lactation period

Children under 3 years of age (solid dosage form)

Drug interactions

Drug interactions occur between thiazide diuretics and the following drugs when used simultaneously.

Alcohol, barbiturates, narcotics or antidepressants:

Orthostatic hypotension may worsen

Antidiabetic drugs (oral drugs and insulin):

Treatment with thiazides may impair glucose tolerance. Dosage adjustments may be necessary. Metformin should be used with caution due to the risk of lactic acidosis due to possible hydrochlorothiazide-induced functional renal failure.

Other antihypertensive substances:

additive effect

Cholestyramine and colestipol resins:

in the presence of anion exchange resins, the ability to absorb hydrochlorothiazide from the gastrointestinal tract deteriorates. Even a single dose of cholestyramine or colestipol resins binds hydrochlorothiazide and reduces its absorption from the gastrointestinal tract by 85 and 43%, respectively.

Pressor amines (for example, adrenaline):

the effect of pressor amines may be reduced, but not to such an extent as to preclude their use.

Non-depolarizing muscle relaxants (for example, tubocurarine):

the muscle relaxant effect may increase.

Lithium:

diuretics reduce the renal clearance of lithium and significantly increase the risk of intoxication with lithium salts. Their simultaneous use is not recommended.

Anti-gout medications (probenecid, sulfinpyrazone and allopurinol):

Dosage adjustment of uric acid depleting agents may be necessary as hydrochlorothiazide may increase serum uric acid levels. The dose of probenecid or sulfinpyrazone may need to be increased. Concomitant administration of thiazides may increase the incidence of hypersensitivity reactions to allopurinol.

Anticholinergics (eg, atropine, biperiden):

due to a decrease in the contractility of the gastrointestinal tract and the gastric emptying interval, the bioavailability of thiazide-type diuretics increases.

Cytotoxic agents (eg, cyclophosphamide, methotrexate):

Thiazides may reduce the renal excretion of cytotoxic drugs and enhance their myelosuppressive effects.

Silicylates:

in case of high doses of salicylates, hydrochlorothiazide may enhance the toxic effect of salicylates on the central nervous system.

Methyldopa:

in some cases, hemolytic anemia may develop with the simultaneous administration of hydrochlorothiazide and methyldopa.

Cyclosporine:

simultaneous use with cyclosporine may increase hyperuricemia and the risk of complications such as gout. Digitalis glycosides:

Digitalis glycosides can provoke the development of arrhythmia against the background of hypokalemia and hypomagnesemia that has developed as a result of the use of Hypothiazide.

Medicines that cause a decrease in potassium levels in the blood: Periodic monitoring of serum potassium levels and ECG is recommended in cases where hydrochlorothiazide is prescribed together with drugs that reduce serum potassium levels (for example, digitalis glycosides, antiarrhythmic drugs) and with the following drugs that cause the development of torsades de pointes (including, some antiarrhythmic drugs), since hypokalemia is a factor contributing to the development of torsade de pointes:

Class Ia antiarrhythmics (eg, quinidine, hydroquinidine, disopyramide)

Class III antiarrhythmics (eg, amiodarone, sotalol, dofetilide, ibutilide)

Certain antipsychotic drugs (eg, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, amisulpiride, tiapride, pimozide, haloperidol, droperidol)

Other drugs (eg, bepridil, cisapride monohydrate, difemanil, erythrocymine IV, halofantrine, mizolastine, pentamidine, terfenadine, vincamine IV).

Calcium salts:

Thiazide diuretics increase serum calcium levels by reducing its excretion. If the prescription of additional components containing calcium is necessary, then in this case the level of calcium in the blood serum should be monitored and the dose should be adjusted accordingly.

Interactions between drugs and laboratory tests:

Due to its effect on calcium metabolism, Hypothiazide may affect the results of studies of parathyroid function (see “Special Instructions”).

Carbamazepine:

Due to the risk of symptomatic hyponatremia, clinical and laboratory monitoring is necessary.

in case of dehydration caused by diuretics, the risk of acute renal failure increases, mainly when using high doses of iodine-containing drugs. In these cases, before prescribing iodine preparations, patients are advised to undergo rehydration.

Amphotericin B (parenteral), corticosteroids, adrenal hormones, and laxatives:

hydrochlorothiazide increases electrolyte imbalance, mainly hypokalemia.

special instructions

Hypotension and water-salt imbalance

As with other types of antihypertensive therapy, symptomatic hypotension may occur in some patients. Patients should be monitored for clinical signs of fluid imbalance (eg, circulating blood volume deficiency, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia), which may occur if diarrhea or vomiting occurs. Serum electrolyte levels should be monitored periodically in such patients. In warmer months, patients with edema may experience euvolemic hyponatremia.

Metabolic and endocrine actions

Treatment with thiazides may decrease glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required (see “Drug Interactions”). During treatment with thiazides, latent diabetes mellitus may occur.

Hypothiazide may reduce renal calcium excretion and may also lead to a transient and mild increase in serum calcium levels. Severe hypercalcemia may be a sign of hidden hyperparathyroidism. Hypothiazide should be discontinued until parathyroid function is examined.

Increases in cholesterol and triglycerides may be associated with diuretic therapy with Hypothiazide.

Treatment with Hypothiazide may cause hyperuricemia and/or gout in some patients.

Liver disease

Hypothiazide should be used with caution in liver disease or in patients with progressive liver disease, since it can cause intrahepatic cholestasis, and the slightest changes in the water-salt balance can trigger the development of hepatic coma. Hypothiazide is contraindicated in patients with severe liver dysfunction (see “Contraindications”).

Other

In patients receiving treatment with Hypothiazide, hypersensitivity reactions may occur if there is a history of allergies or bronchial asthma, as well as in the absence of these diseases. When using thiazides, there was a worsening of the course or activation of systemic lupus erythematosus.

The drug may affect the results of the following laboratory tests:

Reduce plasma levels of PBI (protein-bound iodine)

Treatment with Hypothiazide should be discontinued until laboratory tests of parathyroid function are performed.

Possible increase in the concentration of free bilirubin in the blood serum

Excipients

In case of lactose intolerance, please note that one 25 mg tablet of Hypothiazide also contains 63 mg of lactose monohydrate and one 100 mg tablet of Hypothiazide contains 39 mg of lactose monohydrate.

Pregnancy Experience with the use of hydrochlorothiazide during pregnancy, especially in the first trimester of pregnancy, is limited. Data from preclinical studies are insufficient, and therefore the use of the drug is not recommended.

Hypothiazide penetrates the placental barrier. When used in the second and third trimester of pregnancy, hydrochlorothiazide, due to its pharmacological action, can interfere with fetoplacental blood flow and cause fetal or neonatal jaundice, electrolyte imbalance and thrombocytopenia. Hypothiazide should not be used to treat edema during pregnancy, hypertension or preeclampsia because, instead of beneficial effects on the disease, the risk of plasma volume depletion and uteroplacental circulation impairment increases.

Hypothiazide should not be used to treat primary hypertension in pregnant women, except in rare cases when other therapy cannot be used.

During pregnancy, the use of Hypothiazide is not indicated; the drug is prescribed only in rare cases, if the benefits of using the drug outweigh the risk of possible side effects for the mother and fetus.

Lactation

Hydrochlorothiazide passes into breast milk; its use is contraindicated during lactation. If its use is necessary, breastfeeding should be discontinued (see “Contraindications”).

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

Hypothiazide tablets have a great influence on the ability to drive a vehicle and drive potentially dangerous mechanisms. At the first stage of its application, driving a vehicle or performing hazardous work is prohibited. In the future, the degree of prohibition should be determined taking into account the individual reaction to the drug.

Overdose

Symptoms: the development of symptoms is associated with significant loss of fluid and electrolytes and manifests itself cardiovascular symptoms(tachycardia, arterial hypotension, shock), neurological symptoms ( weakness, confusion, dizziness, muscle spasms, paresthesia, exhaustion, disturbance of consciousness), gastrointestinal symptoms ( nausea, vomiting, thirst), urinary tract symptoms ( polyuria, oliguria or anuria), abnormalities in laboratory tests, more often when renal failure (hypokalemia, hyponatremia, hypochloremia, alkalosis, increased blood urea nitrogen reaction (mainly in renal failure)).

Treatment: there is no specific antidote. Gastric lavage and administration of activated charcoal are recommended. In case of hypotension and shock: replenishment of fluid and blood electrolytes (potassium, sodium, magnesium), monitoring of water-electrolyte balance and renal function until the condition returns to normal.

Release form and packaging

Composition and release form

blister 20 pcs.; 1 blister in a cardboard box.

Description of the dosage form

White or off-white, round, flat tablets with an “H” engraved on one side and a scored line on the other.

pharmachologic effect

Pharmacodynamics

The primary mechanism of action of thiazide diuretics is to increase diuresis by blocking the reabsorption of sodium and chloride ions at the beginning of the renal tubules. By doing this, they increase the excretion of sodium and chlorine and, therefore, water. Excretion of other electrolytes, namely potassium and magnesium, also increases.

At maximum therapeutic doses, the natriuretic/diuretic effect of all thiazides is approximately the same. Natriuresis and diuresis occur within 2 hours and reach their maximum after about 4 hours. They also reduce carbonic anhydrase activity by increasing the excretion of bicarbonate ion, but this effect is usually mild and does not affect urine pH. Hydrochlorothiazide also has antihypertensive properties. Thiazide diuretics have no effect on normal blood pressure.

Pharmacokinetics

Hydrochlorothiazide is incompletely, but rather quickly absorbed from the gastrointestinal tract. This effect lasts for 6-12 hours. After oral administration of a dose of 100 mg, Cmax in blood plasma is achieved after 1.5-2.5 hours.

At the maximum diuretic activity (approximately 4 hours after administration), the concentration of hydrochlorothiazide in the blood plasma is 2 mcg/ml. Plasma protein binding is 40%. It is excreted mainly through the kidneys (filtration and secretion) in unchanged form. T1/2 for patients with normal renal function is 6.4 hours, for patients with moderate renal failure - 11.5 hours, and for patients with creatinine Cl less than 30 ml/min - 20.7 hours.

Hydrochlorothiazide crosses the placental barrier and is excreted into breast milk.

Indications for the drug Hypothiazide ®

arterial hypertension (used both in monotherapy and in combination with other antihypertensive drugs);

edema 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).

Contraindications

hypersensitivity to the drug or to other sulfonamides;

severe renal (creatinine Cl - less than 30 ml/min) or liver failure;

difficult-to-control diabetes mellitus;

Addison's disease:

refractory hypokalemia, hyponatremia, hypercalcemia;

children under 3 years of age (solid dosage form).

Carefully used for hypokalemia, hyponatremia, hypercalcemia, in patients with coronary artery disease, with cirrhosis of the liver, gout, in the elderly, in patients suffering from lactose intolerance, when taking cardiac glycosides.

Use during pregnancy and breastfeeding

Hydrochlorothiazide penetrates the placental barrier. The use of the drug in the first trimester of pregnancy is contraindicated. In the second and third trimesters of pregnancy, the drug can be prescribed only in cases of urgent need, when the benefit to the mother outweighs the potential risk to the fetus and/or child. There is a risk of developing fetal or newborn jaundice, thrombocytopenia and other consequences.

The drug passes into breast milk; therefore, if the use of the drug is absolutely necessary, breastfeeding should be discontinued.

Side effects

Electrolyte imbalance

Hypokalemia, hypomagnesemia, hypercalcemia and hypochloremic alkalosis: dry mouth, thirst, irregular heart rhythm, mood or mental changes, muscle cramps and 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 a gout attack. 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: arrhythmias, orthostatic hypotension, vasculitis.

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

From the hematopoietic organs: very rarely - leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.

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

Interaction

Avoid simultaneous use of the drug with lithium salts(renal clearance of lithium decreases, its toxicity increases).

Carefully use with the following drugs:

Antihypertensive 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 can increase the toxicity of digitalis);

Amiodarone (its use simultaneously with thiazide diuretics may lead to an increased risk of arrhythmias associated with hypokalemia);

Hypoglycemic agents for oral administration (their effectiveness decreases, hyperglycemia may develop);

Corticosteroid drugs, calcitonin (increase the degree of potassium excretion);

NSAIDs (can weaken the diuretic and hypotensive effects of thiazides);

Non-depolarizing muscle relaxants (their effect may be enhanced);

Amantadine (the clearance of amantadine may be reduced by hydrochlorothiazide, resulting in increased plasma concentrations of amantadine and possible toxicity);

Cholestyramine, which reduces the absorption of hydrochlorothiazide;

Ethanol, barbiturates and narcotic analgesics, which enhance the effect of orthostatic hypotension.

Effect of the drug on laboratory test data

Thiazides may reduce plasma levels of protein-bound iodine.

Before testing the function of the parathyroid glands, thiazides should be discontinued. Serum bilirubin concentrations may be increased.

Directions for use and doses

Inside, after meal.

The dosage must be selected individually. With constant medical supervision, the minimum effective dose is established.

Due to the increased loss of potassium and magnesium ions during treatment (serum potassium levels may decrease below 3.0 mmol/l), there is a need to replace potassium and magnesium.

For adults. As an antihypertensive agent The usual initial daily dose is 25-50 mg once, as monotherapy or in combination with other antihypertensive agents. For some patients, an initial dose of 12.5 mg is sufficient, either as monotherapy or in combination. It is necessary to use the minimum effective dose, not exceeding 100 mg/day. If Hypothiazide is combined with other antihypertensive drugs, it may be necessary to reduce the dose of the other drug in order to prevent an excessive decrease in blood pressure.

Hypotensive effect appears within 3-4 days, but it may take up to 3-4 weeks to achieve optimal effect. After completion of treatment, the hypotensive effect persists for 1 week.

Edema syndrome of various origins. The usual starting dose for the treatment of edema is 25-100 mg of the drug once a day or once every 2 days. Depending on the clinical response, the dose may be reduced to 25-50 mg once a day or once every 2 days. In some severe cases, doses up to 200 mg/day may be required at the beginning of treatment.

For premenstrual syndrome, the usual dose is 25 mg/day and is used from the onset of symptoms to the onset of menstruation.

For nephrogenic diabetes insipidus The usual daily dose of 50-150 mg (in several doses) is recommended.

For children. Doses should be set based on the child’s body weight. Usual pediatric daily doses are 1-2 mg/kg or 30-60 mg/m2 body surface, prescribed once a day. The total daily dose for children aged 3 to 12 years is 37.5-100 mg.

Overdose

The most noticeable manifestation of hydrochlorothiazide overdose is acute loss of fluid and electrolytes, manifested by the following signs and symptoms:

Cardiovascular: tachycardia, decreased blood pressure, shock.

Neuromuscular: weakness, confusion, dizziness and spasms of the calf muscles, paresthesia, disturbances of consciousness, fatigue.

Gastrointestinal: nausea, vomiting, thirst.

Renal: polyuria, oliguria or anuria (due to hemoconcentration).

Laboratory indicators: hypokalemia, hyponatremia, hypochloremia, alkalosis, increased levels of urea nitrogen in the blood (especially in patients with renal failure).

Treatment: There is no specific antidote for an overdose of hydrochlorothiazide.

Induction of vomiting and gastric lavage may be ways to eliminate the drug.

Absorption of the drug can be reduced by administering activated carbon. In case of decreased blood pressure or shock, blood volume and electrolytes (potassium, sodium) should be replaced.

Monitor fluid and electrolyte balance (especially serum potassium levels) and renal function until normal values ​​are established.

special instructions

During long-term treatment, it is necessary to carefully monitor the clinical symptoms of water-electrolyte imbalance, primarily in patients at high risk: patients with diseases of the cardiovascular system and impaired liver function; in case of severe vomiting or when signs of water and electrolyte imbalance appear, such as dry mouth, thirst, weakness, lethargy, drowsiness, anxiety, muscle pain or cramps, muscle weakness, hypotension, oliguria, tachycardia, gastrointestinal complaints.

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

Thiazides have been shown to increase urinary magnesium excretion; this may lead to hypomagnesemia.

With reduced renal function, monitoring of creatinine clearance is necessary. In patients with impaired renal function, the drug may cause azotemia, and cumulative effects may develop. If renal dysfunction is obvious, discontinuation of the drug should be considered when oliguria occurs.

In patients with impaired liver function or with progressive liver diseases, thiazides are prescribed with caution, since a slight change in water and electrolyte balance, as well as serum ammonium levels, can cause hepatic coma.

In cases of severe cerebral and coronary sclerosis, the administration of the drug requires special caution.

Treatment with thiazide drugs may impair glucose tolerance. During a long course of treatment for manifest and latent diabetes mellitus, systematic monitoring of carbohydrate metabolism is necessary; It may be necessary to change the dose of hypoglycemic drugs. Increased monitoring of patients with impaired uric acid metabolism is required.

Alcohol, barbiturates, and narcotic analgesics enhance the orthostatic hypotensive effect of thiazide diuretics.

With long-term therapy, in rare cases, pathological changes in the parathyroid glands were observed, accompanied by hypercalcemia and hypophosphatemia. Thiazides can reduce the amount of iodine bound to serum proteins without causing signs of thyroid dysfunction.

In patients suffering from lactose intolerance, gastrointestinal complaints may occur due to the presence of lactose in the tablets: Hypothiazide ® 25 mg tablets contain 63 mg of lactose, Hypothiazide ® 100 mg - 39 mg of lactose.

Impact on the ability to drive a car and perform work that requires increased attention. In the initial stage of using the drug (the duration of this period is determined individually), it is forbidden to drive a car or perform work that requires increased attention.

Conditions for dispensing from pharmacies

On prescription.

Storage conditions for the drug Hypothiazide ®

Keep out of the reach of children.

Shelf life of the drug Hypothiazide ®

Do not use after the expiration date stated on the package.

Synonyms of nosological groups

Diuretic
Drug: HYPOTHIAZIDE®

Active substance of the drug: hydrochlorothiazide
ATX code: C03AA03
CFG: Diuretic
Registration number: P No. 013510/01
Registration date: 11/21/07
Owner reg. credential: CHINOIN Pharmaceutical and Chemical Works Private Co. Ltd. (Hungary)

Hypothiazide release form, drug packaging and composition.

The tablets are white or almost white, round, flat, with an “H” engraving on one side and a scored line on the other. 1 tab. hydrochlorothiazide 25 mg - «- 100 mg
Excipients: magnesium stearate, talc, gelatin, corn starch, lactose monohydrate.
20 pcs. - blisters (1) - cardboard packs.

The description of the drug is based on the officially approved instructions for use.

Pharmacological action Hypothiazide

Diuretic.
The primary mechanism of action of thiazide diuretics is to increase diuresis by blocking the reabsorption of sodium and chloride ions at the beginning of the renal tubules. As a result, the excretion of sodium and chlorine and, consequently, water increases. The excretion of potassium and magnesium also increases.
At maximum therapeutic doses, the diuretic/natriuretic effect of all thiazides is approximately the same. Natriuresis and diuresis occur within 2 hours and reach their maximum after about 4 hours. They also reduce carbonic anhydrase activity by increasing the excretion of bicarbonate ion, but this effect is usually mild and does not affect urine pH.
Hydrochlorothiazide also has antihypertensive properties. Thiazide diuretics have no effect on normal blood pressure.

Pharmacokinetics of the drug.

Suction and distribution
Hydrochlorothiazide is incompletely, but rather quickly absorbed from the gastrointestinal tract. This effect lasts for 6-12 hours. After oral administration of a dose of 100 mg, Cmax 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 the blood plasma is 2 mcg/ml .
Plasma protein binding is 40%.
Removal
The primary route of elimination is by the kidneys (filtration and secretion) in unchanged form. T1/2 for patients with normal renal function is 6.4 hours. T1/2 for patients with moderate renal failure is 11.5 hours. T1/2 for patients with CC<30 мл/мин составляет 20.7 ч. Гидрохлоротиазид проникает через плацентарный барьер и выделяется с грудным молоком.

Indications for use:

Arterial hypertension (as monotherapy, as part of complex antihypertensive therapy);
- edematous syndrome of various origins (including chronic heart failure, nephrotic syndrome, premenstrual tension 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 urinary tract in predisposed patients (reduction of hypercalciuria).

Dosage and method of administration of the drug.

The dose should be selected individually. With constant medical supervision, the minimum effective dose is established. The drug should be taken orally after meals.
For adults
For arterial hypertension, the initial dose is 25-50 mg/day once, as monotherapy or in combination with other antihypertensive drugs. For some patients, an initial dose of 12.5 mg is sufficient (either as monotherapy or in combination). It is necessary to use the minimum effective dose, not exceeding 100 mg/day. When combining hypothiazide with other antihypertensive drugs, it may be necessary to reduce the dose of the other drug to prevent an excessive decrease in blood pressure.
The hypotensive effect appears within 3-4 days, but it may take 3-4 weeks to achieve optimal effect. After completion of therapy, the hypotensive effect persists for 1 week.
For edematous syndrome of various origins, the initial dose is 25-100 mg/day once or once every 2 days. Depending on the clinical response, the dose can be reduced to 25-50 mg/day once or once every 2 days. In some severe cases, at the beginning of treatment, it may be necessary to increase the dose of the drug to 200 mg/day.
For premenstrual tension syndrome, the drug is prescribed at a dose of 25 mg/day and is used from the onset of symptoms until the onset of menstruation.
For nephrogenic diabetes insipidus, the usual daily dose of the drug is 50-150 mg (in several doses).
Due to increased loss of potassium and magnesium ions during treatment (serum potassium levels may be<3.0 ммоль/л) возникает необходимость в замещении калия и магния.
For children
Doses should be set based on the child’s body weight. Usual pediatric daily doses: 1-2 mg/kg body weight or 30-60 mg/m2 body surface area 1 time/day. The daily dose for children aged 3 to 12 years is 37.5-100 mg.

Side effects of Hypothiazide:

From the central nervous system and peripheral nervous system: dizziness, temporarily blurred vision, headache, paresthesia.
From the digestive system: cholecystitis, pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, constipation, anorexia.
From the cardiovascular system: arrhythmia, orthostatic hypotension, vasculitis.
From the urinary system: impaired renal function, interstitial nephritis.
From the hematopoietic system: very rarely - leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.
From the metabolic side: hyperglycemia (a decrease in glucose tolerance can provoke the manifestation of previously latent diabetes mellitus), glucosuria, hyperuricemia (with the development of an attack of gout), hypokalemia, hypomagnesemia, hypercalcemia, hyponatremia (including confusion, convulsions, lethargy, slow thinking, fatigue, excitability, muscle cramps), hypochloremic alkalosis (including dry mouth, thirst, irregular heart rhythm, changes in mood or psyche, muscle cramps and pain, nausea, vomiting, unusual fatigue or weakness) . Hypochloremic alkalosis can cause hepatic encephalopathy or hepatic coma. When using the drug in high doses, an increase in serum lipid levels is possible.
Allergic reactions: urticaria, purpura, necrotizing vasculitis, Stevens-Johnson syndrome, respiratory distress syndrome (including pneumonitis, non-cardiogenic pulmonary edema), photosensitivity, anaphylactic reactions up to shock.
Other: decreased potency.

Contraindications to the drug:

Anuria;
- severe renal failure (CK<30 мл/мин);
- severe liver failure;
- difficult to control diabetes mellitus;
- Addison's disease;
- refractory hypokalemia, hyponatremia, hypercalcemia;
- children under 3 years of age (for solid dosage form);
- hypersensitivity to the components of the drug;
- hypersensitivity to sulfonamide derivatives.
The drug should be used with caution in case of hypokalemia, hyponatremia, hypercalcemia, coronary artery disease, liver cirrhosis, gout, lactose intolerance, use of cardiac glycosides, as well as in elderly patients.

Use during pregnancy and lactation.

The use of the drug is contraindicated in the first trimester of pregnancy. In the second and third trimesters of pregnancy, the use of the drug is possible only if the expected benefit to the mother outweighs the potential risk to the fetus.
Hydrochlorothiazide penetrates the placental barrier. There is a risk of fetal or neonatal jaundice, thrombocytopenia and other consequences.
The drug is excreted in breast milk. If it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be decided.

Special instructions for the use of Hypothiazide.

During long-term course of treatment, clinical symptoms of water-electrolyte imbalance should be carefully monitored, primarily in high-risk patients: patients with diseases of the cardiovascular system, liver dysfunction, severe vomiting or signs of water-electrolyte imbalance (in including dry mouth, thirst, weakness, lethargy, drowsiness, anxiety, muscle pain or cramps, muscle weakness, hypotension, oliguria, tachycardia, gastrointestinal complaints).
The use of potassium-containing drugs or foods rich in potassium (including fruits, vegetables), especially when potassium is lost due to increased diuresis, prolonged diuretic therapy, or concomitant treatment with digitalis glycosides or corticosteroid drugs, helps avoid hypokalemia.
Increased magnesium excretion in urine when using thiazides can lead to hypomagnesemia.
With reduced renal function, monitoring of creatinine clearance is necessary. In patients with impaired renal function, the drug may cause azotemia and the development of cumulative effects. If renal dysfunction is obvious, discontinuation of the drug should be considered when oliguria occurs.
In patients with impaired liver function or progressive liver disease, thiazides should be used with caution, since slight changes in fluid and electrolyte balance, as well as serum ammonium levels, can cause hepatic coma.
In severe cerebral and coronary sclerosis, the use of the drug requires special caution.
Treatment with thiazide drugs may impair glucose tolerance. During a long course of treatment for manifest and latent diabetes mellitus, systematic monitoring of carbohydrate metabolism is necessary due to the potential need to change the dose of hypoglycemic drugs.
Enhanced monitoring of the condition of patients with impaired uric acid metabolism is required.
Alcohol, barbiturates, and opioid analgesics enhance the orthostatic hypotensive effect of thiazide diuretics.
In rare cases, during long-term therapy, pathological changes in the parathyroid glands were observed, accompanied by hypercalcemia and hypophosphatemia.
Thiazides can reduce the amount of iodine bound to serum proteins without causing signs of thyroid dysfunction.
The possibility of gastrointestinal complaints in patients with lactose intolerance should be taken into account, since Hypothiazide 25 mg tablets contain 63 mg of lactose, Hypothiazide 100 mg - 39 mg of lactose.
Impact on the ability to drive vehicles and operate machinery
In the initial stage of using the drug (the duration of this period is determined individually), it is forbidden to drive a car or perform work that requires increased attention.

Drug overdose:

Symptoms: due to the loss of fluid and electrolytes, an overdose of the drug may cause tachycardia, decreased blood pressure, shock, weakness, confusion, dizziness, calf muscle spasms, paresthesia, impaired consciousness, fatigue, nausea, vomiting, thirst, polyuria, oliguria or anuria (due to hemoconcentration), hypokalemia, hyponatremia, hypochloremia, alkalosis, increased levels of urea nitrogen in the blood (especially in patients with renal failure).
Treatment: artificial vomiting, gastric lavage, use of activated carbon. If blood pressure decreases or a state of shock occurs, blood volume and electrolytes (including potassium, sodium) should be replaced. Water and electrolyte balance (especially serum potassium levels) and renal function should be monitored until normal values ​​are established. There is no specific antidote.

Interaction of Hypothiazide with other drugs.

The simultaneous use of hypothiazide with lithium salts should be avoided, since the renal clearance of lithium decreases and its toxicity increases.
With the simultaneous use of Hypothiazide with antihypertensive drugs, their effect is potentiated and there may be a need for dose adjustment.
With simultaneous use of Hypothiazide with cardiac glycosides, hypokalemia and hypomagnesemia associated with the action of thiazide diuretics may increase the toxicity of digitalis.
With simultaneous use of hypothiazide with amiodarone, the risk of arrhythmias associated with hypokalemia increases.
With the simultaneous use of Hypothiazide with oral hypoglycemic agents, the effectiveness of the latter decreases and hyperglycemia may develop.
With simultaneous use of Hypothiazide with corticosteroid drugs and calcitonin, the degree of potassium excretion increases.
With simultaneous use of Hypothiazide with NSAIDs, the diuretic and hypotensive effects of thiazides are weakened.
With simultaneous use of Hypothiazide with non-depolarizing muscle relaxants, the effect of the latter is enhanced.
With the simultaneous use of hypothiazide with amantadine, the concentration and toxicity of the latter increases, resulting in a decrease in its clearance.
With the simultaneous use of hypothiazide with cholestyramine, the absorption of hydrochlorothiazide decreases.
With simultaneous use of Hypothiazide with ethanol, barbiturates and narcotic analgesics, the risk of developing orthostatic hypotension increases.
Thiazides can reduce plasma protein-bound iodine levels; increase the concentration of bilirubin in the blood serum.
Before testing for parathyroid function, thiazides should be discontinued.

Terms of sale in pharmacies.

The drug is available with a prescription.

Terms of storage conditions for the drug Hypothiazide.

The drug should be stored out of the reach of children, protected from light at a temperature of 15° to 25°C. Shelf life – 5 years.