Hypothiazide - instructions for use, dose, side effects, contraindications

The primary mechanism of action of thiazide diuretics is an increase in diuresis by blocking the reabsorption of sodium and chlorine ions at the beginning of the renal tubules. This increases the excretion of sodium and chlorine and, consequently, of water. Excretion of other electrolytes, namely potassium and magnesium, also increases.At the maximum therapeutic doses, the diuretic / natriuretic effect of all thiazides is approximately the same. The natriuresis and diuresis occur within 2 hours and reach their maximum in about 4 hours. They also reduce the activity of carbonic anhydrase by increasing the excretion of the bicarbonate ion, but this action usually manifests itself poorly and does not affect the pH of the urine. Hydrochlorothiazide also has antihypertensive properties. On normal blood pressure, thiazide diuretics have no effect.

Pharmacokinetics:

Hydrochlorothiazide is incomplete, but it is quickly absorbed from the gastrointestinal tract. This action is retained for 6-12 hours. 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%.

Primary way of excretion through the kidneys (filtration and secretion) in unmodified form. The elimination half-life for patients with normal renal function is 6.4 hours, for patients with moderate renal insufficiency is 11.5 hours, and for patients with creatinine clearance less than 30 ml / min - 20.7 hours.

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

Indications:

- Arterial hypertension (used both in monotherapy and in combination with other antihypertensive agents);

- 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 drug or to other sulfonamides;

- anuria;

- severe renal (creatinine clearance below 30 ml / min) or liver failure;

- hard-to-control diabetes mellitus;

- Addison's disease;

- refractory hypokalemia, hyponatremia, hypercalcemia;

- children's age up to 3 years (solid dosage form).

Carefully:

With hypokalemia, hyponatremia, hypercalcemia, in patients with ischemic heart disease, cirrhosis of the liver, gout,in the elderly, in patients suffering from lactose intolerance, when taking cardiac glycosides.

Pregnancy and lactation:

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.

The drug penetrates into the mother's milk; therefore, if the use of the drug is absolutely necessary, then breast-feeding should be discontinued.

Dosing and Administration:

Dosage 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 the treatment (potassium level in the serum may drop below 3.0 mmol / l), there is a need to replace potassium and magnesium.

Adults

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

The hypotensive effect is manifested 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 origins. 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 pre-local syndrome The usual dose is 25 mg per day and is applied from the onset of symptoms before the onset of menstruation.

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

Children

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

Side effects:

Violation of electrolyte balance

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

Hyponatremia: confusion, convulsions, lethargy, slowing down the process of thinking, fatigue, excitability, muscle cramps.

Metabolic phenomena: 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, 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: dizziness, temporarily blurred vision, headache, paresthesia.

On the part of the organs of hematopoiesis: (very rare): leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.

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

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

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, lowering blood pressure, shock.

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

Gastrointestinal: nausea, vomiting, thirst.

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

Laboratory indicators: hypokalemia, hyponatremia, hypochloraemia, alkalosis, an elevated level of urea nitrogen in the blood (especially in patients with renal insufficiency).

Treatment of overdose:

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 case of a decrease in blood pressure or shock, the volume of circulating blood (BCC) and electrolytes (potassium, sodium) should be compensated.

It is necessary to monitor the water-electrolyte balance (especially the potassium level in the serum) and the function of the kidneys until normal values are established.

Interaction:

Medicinal incompatibilities:

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

- Lithium salts (renal clearance of lithium decreases, its toxicity increases).

Use with caution with the following preparations:

- 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, may increase the toxicity of digitalis);

- amiodarone (its use simultaneously with thiazide diuretics can 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 excretion of potassium);

- non-steroidal anti-inflammatory drugs (NSAIDs may weaken the diuretic and hypotensive effect of thiazides);

- Nondepolarizing muscle relaxants (their effect may be increased);

- amantadine (clearance of amantadine may be reduced by hydrochlorothiazide, which leads to an increase in the concentration of amantadine in the plasma and possible toxicity);

- colestyramine, which reduces the absorption of hydrochlorothiazide;

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

Interaction of the preparation / laboratory tests

Thiazides can reduce plasma iodine levels associated with proteins.

Before carrying out tests for the function of parathyroid glands, thiazides should be discarded. The concentration of bilirubin in the serum can be increased.

Special instructions:

With prolonged course treatment, it is necessary to closely monitor the clinical symptoms of water-electrolyte balance disorders, primarily in patients at high risk: patients with cardiovascular disease and liver function disorders; in case of severe vomiting or when signs of disturbance of the water-electrolyte balance appear, such as dry mouth, thirst, weakness, lethargy, drowsiness, anxiety, muscle pain or cramps, muscle weakness, hypotension, oliguria, tachycardia, complaints from the gastrointestinal tract 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 glycosides of digitalis or corticosteroid drugs.

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

With reduced renal function, monitoring of creatinine clearance is necessary. In renal patients, the drug may cause azotemia, and cumulative effects may also develop.If the renal dysfunction is obvious, when oliguria occurs, should consider the possibility of drug discontinuation. Patients with impaired liver function or progressive liver disease should be cautioned with thiazides, since a small change in the water-electrolyte balance, as well as the level of ammonium in the 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 drugs may interfere with glucose tolerance. During a long course of treatment with manifest and latent diabetes, systematic control of carbohydrate metabolism is necessary; it may be necessary to change the dose of hypoglycemic drugs. Enhanced monitoring of patients with impaired uric acid metabolism is required. Alcohol, barbiturates, narcotic analgesics increase the orthostatic hypotensive effect of thiazide diuretics.

With prolonged therapy, in rare cases, a pathological change in the parathyroid glands was observed, accompanied by hypercalcemia and hypophosphatemia.

Thiazides can reduce the amount of iodine that binds to serum proteins without showing signs of a disorder in the thyroid function.

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

Effect on the ability to drive transp. cf. and fur:

In the initial stage of the drug - the duration of this period is determined individually - it is forbidden to drive a car and perform work that requires increased attention.

Form release / dosage:

Tablets, 25 mg and 100 mg.

Packaging:

For 20 tablets of 25 mg per PVC / aluminum blister. 1 blister with instructions for use in a cardboard box.

For 20 tablets of 100 mg in PVC / aluminum blister or in PVC / PVDC / aluminum blister. 1 blister with instructions for use in a cardboard box.

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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013510 / 01

Date of registration:21.11.2007 / 16.06.2016

Expiration Date:Unlimited

The owner of the registration certificate:HINOIN Pharmaceutical and Chemical Products Plant, ZAO HINOIN Pharmaceutical and Chemical Products Plant, ZAO Hungary

Manufacturer: & nbsp

CHINOIN Pharmaceutical and Chemical Works, Co. Ltd. Hungary

Representation: & nbspHINOIN Pharmaceutical and Chemical Products Plant ZAOHINOIN Pharmaceutical and Chemical Products Plant ZAO

Information update date: & nbsp24.04.2017

Illustrated instructions

Instructions

Hypothiazid® (Hypothiazid®)