Hydrochlorothiazide
Latin name: Hydrochlorothiazide
ATX code: C03AA03
Active ingredient: hydrochlorothiazide (Hydrochlorothiazide)
Manufacturer: Atoll LLC (Russia), Pharmstandard-Leksredstva OJSC (Russia), Pranafarm LLC (Russia)
Description and photo update: 2019-10-07
Prices in pharmacies: from 40 rubles.
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Hydrochlorothiazide is a diuretic.
Release form and composition
Dosage form - tablets: round, flat-cylindrical, with a line on one side and chamfers on both sides, almost white or white (10 and 20 pcs. In blister contour packages, 10, 20, 30, 40, 50, 60 and 100 pieces in cans; in a carton box 1, 2, 3, 4, 5, 6, 10 packs or 1 can and instructions for the use of Hydrochlorothiazide).
Composition of 1 tablet:
- active substance: hydrochlorothiazide - 25 or 100 mg;
- auxiliary components: corn starch, microcrystalline cellulose, lactose monohydrate (milk sugar), magnesium stearate, povidone-K25.
Pharmacological properties
Pharmacodynamics
Hydrochlorothiazide is a moderately potent thiazide diuretic.
The drug reduces sodium reabsorption in the cortical segment of Henle's loop without affecting that part of it that passes through the medulla of the kidney. This explains the weaker diuretic effect of hydrochlorothiazide than furosemide.
Hydrochlorothiazide blocks carbonic anhydrase in the proximal section of the convoluted tubules, enhances the kidney excretion of bicarbonates, phosphates, and potassium (in the distal tubules, sodium is exchanged for potassium). Retains calcium ions in the body and excretion of urates. Increases the excretion of magnesium. It has almost no effect on the acid-base state (sodium is excreted together with either chlorine or bicarbonate, therefore, with acidosis, the excretion of chlorides increases, with alkalosis - bicarbonates).
The diuretic effect of hydrochlorothiazide develops within 1-2 hours after taking the drug, reaches a maximum after 4 hours and lasts for 6-12 hours. The effect decreases with a decrease in the glomerular filtration rate, when its value is <30 ml / min - stops.
In patients with diabetes insipidus, hydrochlorothiazide has an antidiuretic effect, that is, it increases the concentration of urine and reduces its volume.
Hydrochlorothiazide changes the reactivity of the vascular wall, reduces the volume of circulating blood and the pressor effect of vasoconstrictors (adrenaline and norepinephrine), and also enhances the depressant effect on the ganglia, thereby reducing high blood pressure (BP). The thiazide diuretic does not affect the level of normal blood pressure.
Pharmacokinetics
After oral administration, the drug is incomplete, but rather quickly absorbed in the gastrointestinal tract. The maximum plasma concentration (C max) after a dose of 100 mg is observed after 1.5–2.5 hours. During the maximum development of the diuretic effect (after about 4 hours), the plasma concentration of hydrochlorothiazide is 2 μg / ml.
Plasma proteins bind about 40%. Hydrochlorothiazide is not metabolized in the liver. It is excreted by the kidneys, mainly unchanged, only about 4% of the dose is excreted (by glomerular filtration and active tubular secretion in the proximal nephron) in the form of 2-amino-4-chloro-m-benzenedisulfonamide (decreases at alkaline urine pH).
In patients with normal renal function, the half-life (T ½) is 6.4 hours, in patients with moderate renal failure [creatinine clearance (CC) 30-50 ml / min) - 11.5 hours, in patients with severe renal failure (CC <30 ml / min) - 20.7 hours.
When hydrochlorothiazide is used in the therapeutic dose range, the average AUC (area under the pharmacological curve) increases in direct proportion to the dose increase. Taking the drug once a day does not lead to a significant accumulation of hydrochlorothiazide in the body.
The drug crosses the placental barrier and into breast milk.
Indications for use
- edematous syndrome of various origins (with portal hypertension, nephrotic syndrome, chronic renal failure, acute glomerulonephritis, premenstrual syndrome, chronic heart failure, corticosteroid treatment);
- arterial hypertension (in monotherapy or in combination with antihypertensive drugs);
- prevention of the formation of stones in the genitourinary tract in predisposed patients (in order to reduce hypercalciuria);
- control of polyuria, mainly in nephrogenic diabetes insipidus.
Contraindications
Absolute:
- anuria;
- severe renal failure (CC less than 30 ml / min);
- refractory hypokalemia, hypercalcemia, hyponatremia;
- Addison's disease;
- difficult to control diabetes mellitus;
- severe liver failure;
- lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome;
- age up to 3 years;
- I trimester of pregnancy;
- hypersensitivity to any component of the drug, other thiazide diuretics or other sulfonamide derivatives.
Relative (hydrochlorothiazide tablets should be used with caution):
- hyponatremia / hypercalcemia / hypokalemia;
- progressive liver disease (due to the risk of developing hepatic coma);
- cirrhosis of the liver (due to the risk of developing hypomagnesemia);
- hypercholesterolemia;
- diabetes;
- cardiac ischemia;
- severe coronary and cerebral sclerosis;
- gout;
- hyperuricemia;
- systemic lupus erythematosus;
- hypertriglyceridemia;
- angle-closure glaucoma;
- myopia;
- elderly age;
- II and III trimesters of pregnancy;
- simultaneous use of cardiac glycosides.
Hydrochlorothiazide, instructions for use: method and dosage
Hydrochlorothiazide tablets should be taken orally, after meals.
The dose is selected individually, accompanying the titration process with medical supervision.
Recommended dosing regimen for adults:
- arterial hypertension: at the beginning of treatment, a dose of 25-50 mg once a day is usually used, but for some patients a dose of 12.5 mg is sufficient. The maximum daily dose is 100 mg. If necessary, other antihypertensive drugs are prescribed in addition, however, when combined with hydrochlorothiazide, a decrease in their dose may be required to avoid an excessive fall in blood pressure. The hypotensive effect develops within 3-4 days, however, it usually takes 3-4 weeks to obtain a stable effect. After discontinuation of the drug, the antihypertensive effect persists for 1 week;
- edematous syndrome of various origins: depending on the clinical situation, the dose may be 25–100 mg once a day, based on the individual response, the dose can be further adjusted to 25–50 mg once a day or once every 2 days. In some cases, an increase in the daily dose to 200 mg is required;
- nephrogenic diabetes insipidus: 50–150 mg per day in several doses, after achieving a therapeutic effect (reduction of polyuria and thirst), the dose may be reduced;
- prevention of stone formation: 50 mg 2 times a day;
- premenstrual syndrome: the recommended dose of hydrochlorothiazide is 25 mg 1 time per day from the first day of the onset of symptoms until the day of the onset of menstruation.
For children, the daily dose of hydrochlorothiazide is determined taking into account body weight - 1–2 mg / kg or 30–60 mg / m 2 of the body surface once a day. The total daily dose for children 3–12 years old can range from 37.5 to 100 mg. After 3-5 days of treatment, it is recommended to take a break for the same number of days. With maintenance therapy, the drug is taken at the recommended dose 2 times a week. In patients receiving an intermittent course of therapy with hydrochlorothiazide taking every 1-3 days or with taking for 2-3 days with a subsequent break, adverse reactions develop less often and decrease in the effectiveness of treatment is less pronounced.
Side effects
The side effects described below are classified according to the frequency of development as follows: very often - more than 1/10; often - more than 1/100, but less than 1/10; infrequently - more than 1/1000, but less than 1/100; rarely - more than 1/10 000, but less than 1/1000; very rarely - less than 1/10 000, including individual messages:
- violations of water and electrolyte balance: often - hypercalcemia, hypomagnesemia, hypokalemia, hyponatremia (manifested by muscle cramps, increased fatigue, slowing down of the thinking process, irritability, excitability, confusion, lethargy, convulsions), hypochloremic alkalosis (manifested by mucous thirst, dry mouth, nausea, vomiting, changes in mood and psyche, arrhythmias, cramps and muscle pains, weakness or unusual fatigue), which can cause hepatic encephalopathy or hepatic coma;
- metabolic disorders: often - glucosuria, hyperglycemia, hyperuricemia with the development of a gout attack, the development of glucose tolerance, the manifestation of latent diabetes mellitus; when using hydrochlorothiazide in high doses - an increase in the concentration of lipids in the blood serum;
- on the part of the cardiovascular system: rarely - orthostatic hypotension, bradycardia, vasculitis;
- on the part of the musculoskeletal system: rarely - muscle weakness;
- on the part of the hematopoietic organs: very rarely - hemolytic / aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia;
- from the digestive system: rarely - sialadenitis, diarrhea, constipation, nausea, vomiting, anorexia, cholestatic jaundice, pancreatitis, cholecystitis;
- from the nervous system and sensory organs: rarely - transient blurred vision, acute attack of angle-closure glaucoma, acute myopia, dizziness, headache, fainting, paresthesia;
- hypersensitivity reactions: rarely - photosensitivity, purpura, skin rash, itching, urticaria, necrotizing vasculitis, Stevens-Johnson syndrome, anaphylactic reactions up to shock, respiratory distress syndrome (including pneumonitis and noncardiogenic pulmonary edema);
- others: exacerbation of systemic lupus erythematosus, interstitial nephritis, impaired renal function, decreased potency.
Overdose
Due to an overdose of Hydrochlorothiazide, fluid and electrolyte loss most often occurs, which is manifested by the following symptoms and signs:
- laboratory parameters: alkalosis, hypochloremia, hyponatremia, hypokalemia, increased concentration of urea nitrogen in the blood (especially in patients with renal failure);
- from the side of the kidneys: anuria, oliguria, polyuria;
- from the gastrointestinal tract: thirst, nausea, vomiting;
- on the part of the cardiovascular system: a marked decrease in blood pressure, tachycardia, shock;
- neuromuscular disorders: paresthesia, spasms of the calf muscles, dizziness, confusion, increased fatigue, impaired consciousness, weakness.
There is no specific antidote for hydrochlorothiazide. After taking an excessive dose, it is recommended to induce vomiting and wash out the stomach, then take activated charcoal. With a pronounced decrease in blood pressure or shock, it is necessary to replace the volume of circulating blood and electrolytes (sodium, potassium). During treatment, it is required to monitor kidney function and water-electrolyte balance. To compensate for potassium deficiency, potassium-sparing diuretics and potassium preparations are prescribed.
special instructions
With prolonged course of treatment, clinical signs of violations of the water and electrolyte balance should be carefully monitored, especially in patients at risk (with impaired liver function and diseases of the cardiovascular system), with prolonged vomiting, and also with the appearance of the following symptoms: thirst, dryness of the mucous membrane oral cavity, marked decrease in blood pressure, tachycardia, drowsiness, weakness (including muscle), muscle pain or cramps, anxiety, complaints from the gastrointestinal tract, oliguria, lethargy.
Hydrochlorothiazide increases the loss of magnesium and potassium ions (the concentration of the latter in the blood serum can decrease to <3 mmol / l), therefore, it is necessary to replenish these electrolytes in the blood. It can also increase the concentration of cholesterol and triglycerides in blood plasma.
If necessary, a study to assess the function of the parathyroid glands Hydrochlorothiazide should be discontinued.
The development of hypokalemia can be prevented by taking potassium-sparing drugs or eating foods rich in potassium (vegetables and fruits). This is especially necessary in patients with increased loss of potassium (in the case of increased diuresis or prolonged treatment) and with the combined use of cardiac glycosides or corticosteroids.
In patients with reduced renal function, it is necessary to regularly monitor creatinine clearance, since the drug can accumulate in them and cause azotemia. If oliguria develops, hydrochlorothiazide should be discontinued.
Particular care should be taken in patients with mild to moderate hepatic impairment and progressive liver disease, since even a small accumulation of ammonium in the blood serum and changes in the water-electrolyte balance can cause hepatic coma.
Thiazide diuretics can cause impaired glucose tolerance. With prolonged use of the drug in patients with manifest and latent diabetes mellitus, it is necessary to periodically monitor the metabolism of carbohydrates, and if necessary, adjust the dose of hypoglycemic agents.
Hydrochlorothiazide can reduce the excretion of calcium by the kidneys, which leads to a moderate transient increase in serum calcium levels, if there is no established violation of calcium metabolism. The identification of severe hypercalcemia is a strong reason to assume that the patient has hyperparathyroidism.
There are known cases of the development of idiosyncratic reactions against the background of diuretic therapy, which led to acute myopia and an acute attack of secondary angle-closure glaucoma. These complications can present with symptoms such as eye pain or sudden loss of visual acuity. They usually appear within a few hours or weeks after starting hydrochlorothiazide. If the patient is not given adequate treatment, acute angle-closure glaucoma can cause permanent vision loss. In this case, the thiazide diuretic should be discontinued as soon as possible. In case of uncontrolled intraocular pressure, urgent medical or surgical treatment may be required. It is believedthat an additional risk factor for the development of acute angle-closure glaucoma is an allergic reaction to penicillin or sulfonamides in history.
There is evidence that thiazide diuretics can provoke an exacerbation of systemic lupus erythematosus or the development of lupus-like reactions. Patients with impaired uric acid metabolism should be under constant medical supervision.
Thiazide diuretics can reduce the amount of iodine that binds to serum proteins, and signs of thyroid dysfunction are not always present.
Against the background of the use of hydrochlorothiazide, it is possible to obtain false positive results during doping control.
Cases of photosensitivity reactions have been reported in individuals receiving thiazide diuretics. With its development, it is recommended to temporarily stop treatment. Where continued therapy is clinically justified, areas of the body exposed to sunlight or UVA should be protected.
There is a risk of developing hypersensitivity reactions even in patients who have no history of allergic reactions or bronchial asthma.
During the period of therapy, it is recommended to refrain from drinking alcohol.
Influence on the ability to drive vehicles and complex mechanisms
Special studies on the effect of hydrochlorothiazide on human motor and cognitive functions have not been conducted. Given the likelihood of such adverse reactions as drowsiness and dizziness, patients are advised to take precautions when driving and working with complex mechanisms, especially during the selection and dose increase.
Application during pregnancy and lactation
During pregnancy, experience with hydrochlorothiazide is limited. The drug is known to cross the placental barrier. In the first trimester of pregnancy, diuretic use is contraindicated. In the second and third trimesters, it is possible to take the drug in exceptional cases, when the benefit to the woman is definitely higher than the potential risk. The risk of fetal / neonatal jaundice, thrombocytopenia and other undesirable effects should be considered.
Although in small quantities, hydrochlorothiazide passes into breast milk, so its use during breastfeeding is not recommended. Women need to stop breastfeeding if treatment is required during lactation.
Pediatric use
Hydrochlorothiazide is contraindicated in children under 3 years of age because of the solid dosage form.
With impaired renal function
- severe renal failure (CC <30 ml / min): the use of hydrochlorothiazide is contraindicated;
- reduced renal function: creatinine clearance should be monitored regularly.
For violations of liver function
- severe hepatic impairment: the use of hydrochlorothiazide is contraindicated;
- progressive liver disease, mild to moderate hepatic impairment: Caution should be exercised.
Use in the elderly
The elderly should be treated with caution.
Drug interactions
Hydrochlorothiazide is not recommended for use in conjunction with the following drugs:
- lithium preparations: the renal clearance of lithium decreases, as a result of which its toxicity increases;
- theophylline: the risk of hypokalemia increases;
- antifungal agents: the likelihood of hypokalemia increases if thiazides are used in combination with amphotericin B; when combined with fluconazole, its maximum plasma concentration increases;
- anxiolytics and hypnotics: the hypotensive effect is enhanced.
Hydrochlorothiazide should be used with caution with the following drugs:
- other antihypertensive drugs: effects are potentiated, which requires dose adjustment;
- cardiac glycosides: hypomagnesemia and hypokalemia that developed while taking a thiazide diuretic can increase the toxicity of cardiac glycosides and increase the risk of arrhythmias;
- pressor amines (for example, epinephrine / adrenaline, norepinephrine / norepinephrine): the severity of the response to their administration decreases;
- glucocorticosteroids, glycyrrhizic acid (contained in licorice root), adrenocorticotropic hormone, calcitonin: increased potassium excretion;
- metformin: in case of violation of renal function while taking hydrochlorothiazide, the risk of lactic acidosis increases;
- hypoglycemic oral drugs, insulin: their effect decreases, there is a risk of hyperglycemia, which may require a dose adjustment;
- amiodarone: arrhythmia due to hypokalemia may occur;
- cholestyramine: absorption of hydrochlorothiazide decreases;
- non-depolarizing muscle relaxants: their effect may increase;
- amantadine: its clearance may decrease, which leads to an increase in plasma concentration and the possible development of toxicity;
- anticholinergic drugs (for example, biperiden, atropine): the bioavailability of hydrochlorothiazide increases due to a decrease in gastrointestinal motility;
- methyldopa: rare cases of hemolytic anemia are known;
- drugs for the treatment of gout (for example, allopurinol, sulfinpyrazone, probenecid): an increase in the content of uric acid in the blood serum is possible (which requires a dose adjustment of hydrochlorothiazide) and the development of hypersensitivity reactions;
- cyclosporine: the likelihood of exacerbation of the course of gout and the development of hyperuricemia increases;
- cytostatic drugs (for example, methotrexate, cyclophosphamide): the myelo-suppressing effect is enhanced due to a slowdown in excretion from the body;
- vitamin D, calcium salts: the risk of hypercalcemia increases;
- barbiturates, agents for general anesthesia, ethanol: the effect of orthostatic hypotension is enhanced;
- non-steroidal anti-inflammatory drugs (including cyclooxygenase-2 inhibitors): a decrease in the diuretic, hypotensive and natriuretic effects of hydrochlorothiazide is possible. In patients with functional impairment of the kidneys (for example, in persons with dehydration and the elderly), receiving angiotensin II receptor antagonists or angiotensin-converting enzyme inhibitors, there is a risk of further deterioration of renal function, up to the development of acute renal failure. These effects are reversible;
- carbamazepine: the risk of developing symptomatic hyponatremia increases.
Hydrochlorothiazide can reduce the concentration of iodine bound to proteins in the blood plasma.
During therapy, an increase in the serum bilirubin content is possible.
Due to the risk of pirouette-type ventricular tachycardia, serum potassium levels and an electrocardiogram should be monitored regularly when taking cardiac glycosides or the following drugs that prolong the QT interval:
- class IA antiarrhythmics (disopyramide, quinidine);
- class III antiarrhythmics (dofetilide, amiodarone), sotalol;
- some antipsychotics (chlorpromazine, sulpiride, haloperidol, thioridazine, trifluoperazine, tiapride, levomepromazine, amisulpride, droperidol);
- some other drugs (erythromycin and vincamine for intravenous administration, halofantrine, diphemanil methyl sulfate, sparfloxacin, cisapride, mizolastine, ketanserin, terfenadine).
Analogs
Hydrochlorothiazide analogs are: Acripamide, Acetazolamide, Hydrochlorothiazide-SAR, Britomar, Hypothiazide, Diacarb, Diuver, Indap, Indapamide, Indapamide Long Richter, Ionic, Lazix, Lorvas SR, Mannitol-Mannitol-Sunnitol, Mannitol-Sone, Oxodolin, Retapres, Ravel SR, Tenzar, Torasemid, Torasemid-SZ, Trigrim, Furosemide, etc.
Terms and conditions of storage
Store in a dark place, out of reach of children, at a temperature not exceeding 25 ° C.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews of Hydrochlorothiazide
According to reviews, Hydrochlorothiazide is an effective diuretic. However, it is not recommended for long-term use as monotherapy, as it causes electrolyte loss.
There are no reports of the development of pronounced adverse reactions.
Price for Hydrochlorothiazide in pharmacies
The cost of the drug depends on the manufacturer, dosage and number of tablets in the package. The approximate price for Hydrochlorothiazide 25 mg (20 pieces per package) is 35–49 rubles, Hydrochlorothiazide 100 mg (20 pieces per package) - 39–58 rubles.
Hydrochlorothiazide: prices in online pharmacies
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Drug name Price Pharmacy |
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Hydrochlorothiazide 25 mg tablets 20 pcs. RUB 40 Buy |
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Hydrochlorothiazide tablets 25mg 20 pcs. RUB 47 Buy |
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Hydrochlorothiazide 100 mg tablets 20 pcs. RUB 55 Buy |
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Hydrochlorothiazide + Losartan 50 mg + 12.5 mg film-coated tablets 30 pcs. 207 r Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
