Hydrochlorothiazide-SAR - instructions for use, dose, side effects, contraindications

Pharmacodynamics:Thiazide diuretic of average duration of action. Reduces sodium reabsorption at the level of the cortical segment of the Henle loop, without affecting its area passing through the medulla of the kidneys. It blocks the carbonic anhydrase in the proximal part of the convoluted tubules, increases the excretion of potassium ions in the urine (in the distal canals of sodium ions it is exchanged for potassium ions), hydrocarbonates and phosphates.Virtually does not affect the acid-base state (sodium ions are eliminated either with chlorine ions or with hydrocarbonate, so with alkalosis, the excretion of hydrocarbonates increases, with acidosis - chloride). Increases the excretion of magnesium ions, delays in the body calcium ions and excretion of urates. The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, lasts 10-12 hours. The effect decreases with a decrease in the glomerular filtration rate and stops at a value of less than 30 ml / min. Thiazides have no effect on normal blood pressure (BP). Antihypertensive effect occurs after 3.4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect. 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 vasoconstrictive drugs (epinephrine, norepinephrine) and enhancing the depressor effect on the ganglion.

Pharmacokinetics:

After ingestion, 60-80% of the dose is absorbed from the gastrointestinal tract. Connection with blood plasma proteins - 40-60%. Bioavailability is 70%, the diuretic effect occurs after 2 hours, reaches a maximum after 4 hours and lasts up to 12 hours.

The removal of hydrochlorothiazide from the plasma has a two-phase character: the half-life in the initial phase is 2 h, in the terminal phase - about 10 h.

With renal failure with creatinine clearance less than 30 ml / min - half-life is 20.7 hours.

In the therapeutic range of doses, the average area under the curve (concentration - time) increases in direct proportion to the increase in dose, with the appointment of once a day, cumulation is negligible. Penetrates through the hematoplacental barrier and into breast milk. The half-life of the drug is 6-15 hours. It is not metabolized by the liver. It is excreted by the kidneys: 95% unchanged and about 4% in the form of hydrolyzate-2-amino-4-chloro-m-benzene disulfonamide (reduced in alkaline urine) by glomerular filtration and active tubular secretion in the proximal nephron. In elderly patients and with renal dysfunction, clearance of hydrochlorothiazide significantly decreases, which leads to a significant increase in its concentration in the blood plasma.The decrease in clearance, noted in elderly patients, appears to be associated with impaired renal function. In patients with cirrhosis of the liver, there is no change in the pharmacokinetics of hydrochlorothiazide.

Indications:Arterial hypertension (in monotherapy or 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 urinary tract in predisposed patients (reduced hypercalciuria).

Contraindications:Hypersensitivity to the drug or other sulfonamides; anuria; severe renal (creatinine clearance below 30 ml / min) or liver failure; difficultly controlled diabetes mellitus; Addison's disease; refractory hypokalemia, hyponatremia; hypercalcemia; children's age up to 3 years (solid dosage form); patients with rare, hereditary diseases, such as lactose intolerance,deficiency of lactose or glucose-galactose malabsorption (lactose is included in the formulation); pregnancy (I trimester), lactation.

Carefully:With hypokalemia, hyponatremia, hypercalcemia, in patients with ischemic heart disease, cirrhosis of the liver, gout; in the elderly; with the admission of cardiac glycosides, II-III trimesters of pregnancy, severe cerebral and coronary sclerosis.

Pregnancy and lactation:

The drug is contraindicated in the first trimester of pregnancy and during breastfeeding.

Use in the II and III trimester of pregnancy is possible only in case of strict necessity, when the prospective benefit for the mother exceeds the potential risk to the fetus.

Dosing and Administration:

The drug is administered orally, regardless of food intake. With edematic syndrome (depending on the condition and reaction of the patient), 25-100 mg is prescribed in a daily dose, taken once (in the morning) or in 2 divided doses (in the morning).

The elderly are 12.5 mg 1-2 times a day.

Children from 3 to 12 years - 100 mg / day, dividing into 2-3 admission. 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.When using intermittent course of treatment with taking 1-3 days or 2-3 days followed by a break, the decrease in efficiency is less pronounced, and the side effects develop less often.

To reduce blood pressure: inside, 25-50 mg / day, with a slight diuresis and natriuresis only on the first day of admission (prescribed long-term in conjunction with other antihypertensive drugs: vasodilators, angiotensin converting enzyme inhibitors, sympatholytic drugs, beta-adrenoblockers) . With an increase in the dose from 25 to 100 mg, there is a proportional increase in diuresis, natriuresis and a decrease in blood pressure. In a single dose of more than 100 mg - an increase in diuresis and a further decrease in blood pressure are insignificant, a disproportionate increase in the loss of electrolytes is observed, especially potassium ions and magnesium ions. An increase in the dose of more than 200 mg is not appropriate, because increased diuresis does not occur.

To reduce intraocular pressure appoint 25 mg once every 1-6 days; the effect occurs in 24-48 hours. In diabetes insipidus - 25 mg 1-2 times a day with a gradual increase in the dose (daily dose of -100 mg) to achieve therapeutic effect (reducing thirst and polyuria), in the future, a dose reduction is possible.

Side effects:

Violations of the electrolyte balance:

- hypokalemia, hypomagnesemia, hypercalcemia and hypochloraemic alkalosis: dry mouth, thirst, irregular heart rhythm, changes in mood or psyche, cramps and muscle pains, 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, as a consequence of which latent diabetes mellitus can manifest itself. When using high doses, serum lipid levels may increase.

From the central and peripheral nervous system: dizziness, transient visual impairment, headache, paresthesia.

From the digestive system: cholecystitis, pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, constipation, anorexia.

From the cardiovascular system: arrhythmia, orthostatic hypotension, vasculitis.

Overdose:

Symptoms: lowering blood pressure, tachycardia, shock, weakness, confusion, dizziness and spasms of the calf muscles, paresthesia, impaired consciousness, fatigue; nausea, vomiting, thirst; polyuria, oliguria or anuria (due to hemoconcentration); hypokalemia (adynamia, paralysis, constipation, arrhythmias), hyponatremia, hypochloraemia, alkalosis, increased urea concentration in the blood (especially in patients with renal insufficiency).

Treatment: there is no specific antidote. Gastric lavage; reception of activated charcoal, in case of a decrease in blood pressure or shock, the volume of circulating blood and electrolytes should be reimbursed (potassium, sodium). It is necessary to monitor the water-electrolyte balance (especially the level of potassium in the serum) and the function of the kidneys.

Interaction:

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

With caution should be used with antihypertensive drugs (increasing their effect, may require dose adjustment); cardiac glycosides (hypokalemia andhypomagnesemia with thiazide diuretics may increase the toxicity of cardiac glycosides); amiodarone (risk of arrhythmias associated with hypokalemia); hypoglycemic agents for oral administration (their effectiveness decreases, the risk of developing hyperglycemia); corticosteroid drugs, calcitonin (increased hypokalemia); non-steroidal anti-inflammatory drugs (weaken the diuretic and antihypertensive effect of thiazides); Nondepolarizing muscle relaxants (their effect may be increased); amantadine (clearance of amantadine may decrease, which leads to an increase in the concentration of amantadine in the plasma and possible toxicity); cole-styramine (lowers the absorption of hydrochlorothiazide); ethanol, barbiturates and narcotic analgesics, which increase the risk of developing orthostatic hypotension.

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

Special instructions:

With long-term treatment, it is necessary to closely monitor the clinical symptoms of water-electrolyte imbalance, primarily in patients at high risk: patients with cardiovascular disease and impaired liver function.Hypokalemia can be avoided by the use of potassium-containing drugs or foods rich in potassium (fruits, vegetables), especially in case of increased potassium loss (severe diuresis, prolonged treatment) or simultaneous treatment with cardiac glycosides or corticosteroid drugs.

Increases the excretion of magnesium in the urine, which can lead to hypomagnesemia.

With reduced renal function, CC control is necessary. In renal patients, the drug can accumulate and cause the development of azotemia. With the development of oliguria should consider the possibility of discontinuing the drug.

With mild and moderate hepatic insufficiency or progressive liver disease hydrochlorothiazide prescribe with caution, because a small change in the water-electrolyte balance and the accumulation 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.

May interfere with glucose tolerance. During a long course of treatment with manifest and latent diabetes, systematic control of carbohydrate metabolism is necessary; may require a dose adjustment of hypoglycemicmeans. During the treatment period, periodic monitoring of the concentration of uric acid is necessary. Alcohol, barbiturates, narcotic analgesics intensify the antihypertensive effect of thiazide diuretics.

With prolonged therapy, in rare cases, a pathological change in the function of the parathyroid glands was observed, accompanied by hypercalcemia and hypophosphatemia. It can affect the results of laboratory studies of the function of parathyroid glands, so the drug should be discarded before determining the function of the parathyroid glands. Hydrochlorothiazide can reduce the amount of iodine binding to whey proteins, without manifestations of thyroid dysfunction.

Effect on the ability to drive transp. cf. and fur:At the beginning of therapy with the drug (the duration of this period is determined individually), it is recommended to refrain from driving vehicles and performing work that requires increased concentration, attention and speed of psychomotor reactions (due to the possible development of dizziness and drowsiness), and further caution should be exercised.

Form release / dosage:

Tablets of 25 mg.

Packaging:10 tablets in a planar cell package.5 contour cell packs of 10 tablets with instructions for use are placed in a pack of cardboard.

Storage conditions:In a dry place, protected from light and inaccessible to children.

Shelf life:2 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003748 / 01

Date of registration:02.10.2009 / 29.09.2015

Expiration Date:Unlimited

The owner of the registration certificate:Promomed Rus, Open CompanyPromomed Rus, Open Company Russia

Manufacturer: & nbsp

BIOCHEMIST, OJSC Russia

Representation: & nbspPROMO-MED LLC PROMO-MED LLC Russia

Information update date: & nbsp16.04.2017

Illustrated instructions

Instructions

Hydrochlorothiazide-CAP® (Hydrochlorthiazide-SAR®)