Hypothiazid

General characteristics. Structure:

Tablets of 25 mg

Active agent - a hydrochlorothiazide of 25 mg.

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

Tablets of 100 mg

Active agent - a hydrochlorothiazide of 100 mg.

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

Description

White or almost white round flat tablets with an engraving of "N" on one party and risky on another.

Pharmacological properties:

Pharmacodynamics. Primary mechanism of effect of thiazide diuretics is increase in a diuresis by blocking of a reabsorption of ions of sodium and chlorine at the beginning of renal tubules. It they raise excretion of sodium and chlorine and, therefore, water.

Excretion of other electrolytes, namely, potassium and magnesium, also increases. In the maximum therapeutic doses the diuretic/natriuretic effect of all tiazid is approximately identical. They also reduce activity of a karboangidraza by removal strengthening ion bicarbonate, but this action is usually shown poorly and does not influence on рН urine. The hydrochlorothiazide has also hypotensive properties. Thiazide diuretics of influence do not render on normal arterial pressure.

Pharmacokinetics. A hydrochlorothiazide it is incomplete, however it is quickly enough soaked up from digestive tract. This action remains within 6-12 hours. After intake of a dose in 100 mg the maximum concentration in a blood plasma is reached in 1,5-2,5 hours. On a maximum of diuretic activity (approximately in 4 hours after reception) concentration of a hydrochlorothiazide in a blood plasma makes 2 mkg/ml. Communication with proteins of a blood plasma makes 40%. Primary way of removal through kidneys (filtering and secretion) in not changed form. The elimination half-life for patients with normal renal function makes 6,4 hours, for patients with a moderate renal failure - 11,5 hours, and for patients with clearance of creatinine less than 30 ml/min. - 20,7 hours. The hydrochlorothiazide gets through a placental barrier and is excreted in breast milk.

Indications to use:

• arterial hypertension (it is used both in monotherapy, and in a combination with other anti-hypertensive means);
• edematous syndrome of various genesis (chronic heart failure, nephrotic syndrome, premenstrual syndrome, acute glomerulonephritis, chronic renal failure, portal hypertensia, treatment by corticosteroids);
• control of a polyuria, it is preferential at a nephrogenic not diabetes mellitus;
• prevention of formation of stones in an urinogenital path at predisposed patients (reduction of a hypercalcuria).

Route of administration and doses:

The dosage has to be picked up individually. At constant medical control minimum effective dose is established. A pill should be taken after food.

Due to the strengthened loss of potassium ions and magnesium in the course of treatment (potassium level in serum can fall lower than 3,0 mmol/l), there is a need for substitution of potassium and magnesium.

Adults

As anti-hypertensive means: the usual initial daily dose makes 25-50 mg once, in the form of monotherapy or in a combination with other anti-hypertensive means. Some patient of rather initial dose in 12,5 mg both in the form of monotherapy, and in a combination. It is necessary to apply minimum effective dose which is not exceeding 100 mg a day. If Hypothiazid is combined with other hypotensive drugs, there can be a need to lower a dose of other drug to warn an excessive lowering of arterial pressure (ABP).

Hypotensive action is shown within 3-4 days, however, for achievement of optimum effect can be required up to 3 - 4 weeks. After the end of treatment the hypotensive effect remains within one week.

Edematous syndrome of various genesis: a usual initial dose at treatment of hypostases are 25-100 mg of drug of 1 times a day or 1 time in two days. Depending on clinical reaction the dose can be lowered to 25 - 50 mg of 1 times a day or 1 time in two days. In some hard cases in an initiation of treatment doses to 200 mg a day can be required.

At a predmestrualny syndrome the usual dose makes 25 mg a day and is applied from the beginning of manifestation of symptoms prior to the beginning of periods.

At a nephrogenic not diabetes mellitus the usual daily dose of 50-150 mg is recommended (in stages).

Children 

Doses have to be established, proceeding from the body weight of the child. Usual pediatric daily doses, 1-2 mg/kg of body weight or 30-60 mg on square meter of a body surface, are appointed once a day.

The general daily dose to children aged from 3 up to 12 years - on 37,5-100 mg a day.

Features of use:

At long course treatment it is necessary to control carefully clinical symptoms of disturbance of water and electrolytic balance, first of all, at patients of group of the increased risk: patients with diseases of cardiovascular system and abnormal liver functions; in case of severe vomiting or at emergence of signs of disturbance of water and electrolytic balance, such as dryness in a mouth, thirst, weakness, a lethargy, drowsiness, concern, muscular pains or spasms, muscular weakness, hypotension, an oliguria, tachycardia, complaints from digestive tract.

The hypopotassemia can be avoided use of kaliysoderzhashchy drugs or the food rich with potassium (fruit, vegetables), especially in case of the strengthened potassium loss (a profound diuresis, long treatment) or simultaneous treatment by glycosides of a foxglove or corticosteroid drugs.

It is shown that tiazida increase removal of magnesium with urine; it can lead to a hypomagnesiemia.

At the lowered renal function control of clearance of creatinine is necessary. Drug can cause an azotemia in renal patients, and also cumulative effects can develop. If the renal failure is obvious, at approach of an oliguria it is necessary to weigh a possibility of drug withdrawal. The patient with the broken function of a liver or with the progressing diseases of a liver of a tiazida appoint with care as little change of water and electrolytic balance, and also ammonium level in serum, can cause a hepatic coma.

In case of a heavy cerebral and coronary sclerosis purpose of drug demands extra care.

Treatment by thiazide drugs can break portability of glucose. During a long course of treatment at a manifest and latent diabetes mellitus systematic control of metabolism of carbohydrates is necessary; there can be a need for change of a dose of hypoglycemic drugs. The strengthened control of patients with the broken metabolism of uric acid is required. Alcohol, barbiturates, drugs strengthen orthostatic hypotensive effect of thiazide diuretics.

At long therapy the pathological change of epithelial bodies which is followed by a hypercalcemia and a hypophosphatemia was in rare instances observed. Tiazida can reduce amount of the iodine contacting serum proteins without manifestation of signs of disorder of function of a thyroid gland.

At the patients having a lactose intolerance emergence of gastrointestinal complaints, in connection with availability of lactose as a part of Hypothiazid tablets is possible: tablets of 25 mg contain 63 mg of lactose, tablets of 100 mg - 39 mg of lactose.

Influence on ability to drive the car and to perform the works requiring special attention

In an initial stage of use of drug duration of this period is defined individually - it is forbidden to drive the car and to perform the works requiring special attention.

Side effects:

Disturbance of electrolytic balance
• Hypopotassemia, hypomagnesiemia, hypercalcemia and gipokhloremichesky alkalosis: dryness in a mouth, thirst, an irregular heart rhythm, changes in mood or mentality, spasms and muscle pains, nausea, vomiting, unusual fatigue or weakness. The Gipokhloremichesky alkalosis can cause hepatic encephalopathy or a hepatic coma.
• Hyponatremia: confusion of consciousness, convulsion, lethargy, delay of process of thinking, fatigue, excitability, muscular spasms.

Metabolic phenomena: a hyperglycemia, a glucosuria, hyperuricemias with development of an attack of gout.

Treatment of a tiazidama can reduce tolerance to glucose, and the diabetes mellitus latentno proceeding can be demonstrated. At use of high doses levels of lipids in blood serum can increase.

From digestive tract: cholecystitis or pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, lock, anorexia.

From cardiovascular system: arrhythmias, orthostatic hypotension, vasculitis.

From a nervous system: dizziness, temporarily indistinct sight, headache, paresthesias.

From bodies of a hemopoiesis: (very seldom): leukopenia, agranulocytosis, thrombocytopenia, hemolitic anemia, aplastic anemia.

Hypersensitivity reactions: a small tortoiseshell, a purpura, a necrotic vasculitis, Stephens-Johnson's syndrome, a respiratory distress syndrome (including a pneumonitis and not cardiogenic hypostasis of a lung), photosensitivity, anaphylactic reactions up to shock.

Other phenomena: decrease in a potentiality, disturbance of renal function, intersticial nephrite.

Interaction with other medicines:

Medicinal incompatibility

It is necessary to avoid simultaneous use of drug with:
• lithium salts (the renal clearance of lithium decreases, its toxicity increases).

With care to apply with the following drugs:
• anti-hypertensive drugs (their action is exponentiated, need for dose adjustment can appear)
• cardiac glycosides (the hypopotassemia and a hypomagnesiemia interfaced to effect of thiazide diuretics can increase toxicity of a foxglove)
• Amiodaronum (its use along with thiazide diuretics can lead to increase in risk of the arrhythmias connected with a hypopotassemia)
• hypoglycemic means for intake (their efficiency decreases, the hyperglycemia can develop)
• corticosteroid drugs, a calcitonin (increase extent of removal of potassium)
• non-steroidal anti-inflammatory drugs (NPVS can weaken diuretic and hypotensive action of tiazid)
• not depolarizing muscle relaxants (their effect can amplify)
• amantadiny (the clearance of an amantadin can decrease a hydrochlorothiazide that leads to increase in concentration of an amantadin in plasma and possible toxicity)
• Colestyraminum which reduces absorption of a hydrochlorothiazide
• ethanol, barbiturates and drugs which strengthen effect of orthostatic hypotension

Laboratory analyses

Tiazida can reduce level in plasma of the iodine connected with proteins.

Before carrying out analyses on function of epithelial bodies of a tiazida it is necessary to cancel. Concentration of bilirubin in blood serum can be increased.

Contraindications:

• hypersensitivity to drug or to other sulfonamides;
• anury;
• heavy renal (the clearance of creatinine is lower than 30 ml/min.) or a liver failure;
• unmanageable diabetes mellitus;
• Addison's disease;
• refractory hypopotassemia, hyponatremia, hypercalcemia;
• children's age to the 3rd (a firm dosage form).

With care to apply at a hypopotassemia, a hyponatremia, a hypercalcemia, at patients with coronary heart disease, cirrhosis, gout, streets of advanced age, at the patients suffering from a lactose nepernosimost at reception of cardiac glycosides.

Pregnancy and period of feeding by a breast

The hydrochlorothiazide gets through a placental barrier. Use of drug in the first trimester of pregnancy is contraindicated. In the second and third trimesters of pregnancy drug can be appointed only in case of emergency when the advantage for mother exceeds potential risk for a fruit and/or the child. There is a danger of jaundice of a fruit or newborns, thrombocytopenia and other effects.

Drug gets into maternal milk; therefore if use of drug is absolutely necessary, then feeding by a breast should be stopped.

Overdose:

The most noticeable manifestation of overdose by a hydrochlorothiazide is the acute loss of liquid and electrolytes which is expressed in the following signs and symptoms:

Cardiovascular: tachycardia, lowering of arterial pressure (ABP), shock.

Neuromuscular: weakness, confusion of consciousness, dizziness and systremmas, paresthesia, consciousness disturbances, fatigue.

Gastrointestinal: nausea, vomiting, thirst.

Renal: a polyuria, an oliguria or an anury (because of haemo concentration).

Laboratory indicators: a hypopotassemia, a hyponatremia, a hypochloraemia, an alkalosis, the increased level of ureal nitrogen in blood (especially at patients with a renal failure).

Overdose treatment: there is no specific antidote at overdose by a hydrochlorothiazide.

Induction of vomiting, gastric lavage can be ways of removal of drug. Absorption of drug can be reduced, applying absorbent carbon. In case of decrease in the ABP or shock it is necessary to compensate the volume of the circulating blood (VCB) and electrolytes (potassium, sodium).

It is necessary to watch water and electrolytic balance (especially potassium level in serum) and function of kidneys before establishment of normal values.

Storage conditions:

In the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity of 5 years. Not to use after the date specified on packaging.

Issue conditions:

Without recipe

Packaging:

Tablets of 25 mg and 100 mg. On 20 tablets in PVC / the aluminum blister. On 1 blister together with the application instruction in a cardboard pack.