Instructions Hydrochlorothiazide tablets 25 mg No. 20
Composition
active ingredient: hydrochlorothiazide;
1 tablet contains hydrochlorothiazide (calculated as 100% dry matter) – 25 mg;
Excipients: lactose monohydrate, povidone, microcrystalline cellulose, corn starch, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: tablets of white or white with a yellowish tinge, with a biconvex surface. Marbling and gray inclusions are allowed on the surface of the tablets.
Pharmacotherapeutic group
Diuretics with moderate activity, thiazide group. Simple thiazide diuretics. Hydrochlorothiazide. ATC code C0ZA A03.
Pharmacological properties
Pharmacodynamics.
Hydrochlorothiazide is a thiazide diuretic of medium potency. It reduces the reabsorption of sodium ions at the level of the cortical segment of the loop of Henle, without affecting the section that passes in the medulla of the kidney. Hydrochlorothiazide blocks carbonic anhydrase in the proximal convoluted tubule, accelerates the excretion of potassium ions, bicarbonates and phosphates in the urine. It practically does not affect the state of acid-base balance (sodium ions are excreted either together with chlorine ions or with bicarbonate ions, therefore, in alkalosis, the excretion of bicarbonates is increased, in acidosis - chlorides). Hydrochlorothiazide increases the excretion of magnesium ions, delays the excretion of urates. Hydrochlorothiazide reduces the excretion of calcium in the urine, reducing the formation of calcium kidney stones.
Hydrochlorothiazide has a hypotensive effect. The antihypertensive effect occurs after 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect. The hypotensive effect persists for a week after discontinuation of the drug.
The effect of hydrochlorothiazide decreases with a decrease in glomerular filtration rate and ceases when creatinine clearance is less than 30 ml/min.
Non-melanoma skin cancer. Results from two pharmacoepidemiological studies based on data from the Danish National Cancer Registry demonstrated a cumulative dose-dependent association between hydrochlorothiazide (HCTZ) and the occurrence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
One study included a population of 71,533 patients with BCC and 8,629 patients with PCC, who were compared with 1,430,833 and 172,462 control patients, respectively. High-dose HCT use (≥ 50,000 mg cumulative) was associated with an adjusted hazard ratio (HR) of 1.29 (95% confidence interval (CI): 1.23-1.35) for BCC and 3.98 (95% CI: 3.68-4.31) for PCC. A clear cumulative dose-dependent relationship was observed for both BCC and PCC.
Another study showed a possible association between lip cancer (LC) and HRT use: 633 cases of lip cancer (LC) were compared with 63,067 control patients using a random sampling strategy. A cumulative dose-dependent association was demonstrated with an adjusted HR of 2.1 (95% CI: 1.7-2.6), increasing to HR of 3.9 (3.0-4.9) for high doses (25,000 mg) and HR of 7.7 (5.7-10.5) for the highest cumulative dose (100,000 mg) (see section 4.4).
Pharmacokinetics.
After ingestion, hydrochlorothiazide is rapidly but incompletely (60-80%) absorbed from the gastrointestinal tract. The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours and lasts for 10-12 hours. Binding to plasma proteins is 40%. Hydrochlorothiazide penetrates the placental barrier and into breast milk.
Hydrochlorothiazide is not significantly metabolized. The primary route of elimination is renal excretion in unchanged form. The half-life in patients with normal renal function is about 6 hours, in patients with moderate renal insufficiency - 11.5 hours.
Indication
Edema syndrome of various genesis (in congestive heart failure, cirrhosis of the liver with ascites, nephrotic syndrome, chronic renal failure, premenstrual syndrome, fluid retention in obesity, as well as caused by taking medications, such as corticosteroids);
arterial hypertension (as monotherapy or in combination with other antihypertensive drugs);
symptomatic treatment of nephrogenic diabetes insipidus (to reduce polyuria);
subcompensated forms of glaucoma;
prevention of the formation of calcium kidney stones.
Contraindication
Hypersensitivity to hydrochlorothiazide, other sulfonamides or to any component of the drug;
severe renal failure (creatinine clearance below 30 ml/min);
mechanical obstruction of the urinary tract;
severe liver failure, hepatic encephalopathy;
anury;
gout (severe forms);
hypovolemia;
decompensated diabetes mellitus;
disturbances of water-salt metabolism (hypokalemia, hypercalcemia, hyponatremia).
Interaction with other medicinal products and other types of interactions
Amphotericin B (parenteral), laxatives that stimulate intestinal motility, glucocorticosteroids, adrenocorticotropic hormone, calcitonin: hydrochlorothiazide may enhance electrolyte imbalance, especially hypokalemia.
Calcium salts and vitamin D: Thiazide diuretics reduce calcium excretion and may increase plasma calcium levels. Serum calcium levels should be monitored and the dose of calcium/vitamin D should be adjusted.
Drugs that cause changes in serum potassium levels: increased risk of cardiac arrhythmias, including ventricular tachycardia (e.g., torsade de pointes):
Class Ia antiarrhythmic drugs (e.g. quinidine, hydroquinidine, disopyramide);
class III antiarrhythmic drugs (e.g. amiodarone, sotalol, dofetilide, ibutilide);
neuroleptics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpiride, tiapride, pimozide, haloperidol, droperidol);
others (e.g., bepridil, cisapride, diphemanil, erythromycin, halofantrine, mizolastine, pentamidine, terfenadine, vincamine).
Carbamazepine: development of hyponatremia. Electrolyte levels should be monitored and, if necessary, other diuretics should be used.
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid > 3 g/day and non-selective NSAIDs: NSAIDs may reduce the antihypertensive effect of hydrochlorothiazide and increase the effect of hydrochlorothiazide on serum potassium when administered concomitantly.
Difluzanil: increases the concentration of hydrochlorothiazide in the blood plasma and reduces its hyperuricemic effect.
Ethanol, barbiturates (e.g. phenobarbital), diazepam, narcotic analgesics, antidepressants: may enhance the hypotensive effect of hydrochlorothiazide.
Pressor amines (e.g. epinephrine, norepinephrine): hydrochlorothiazide reduces their effect on blood pressure.
Antihypertensive drugs: when used together with hydrochlorothiazide, it may be necessary to reduce the dose of antihypertensive drugs to prevent excessive reduction in blood pressure.
Lithium salts: simultaneous use with hydrochlorothiazide should be avoided due to the possibility of increasing the concentration of lithium salts in the blood plasma to toxic levels.
Antidiabetic drugs (oral agents, insulin): during treatment with thiazides, impaired glucose tolerance and hyperglycemia may occur. Dosage adjustment may be required.
Metformin: Use with caution due to the risk of lactic acidosis due to possible hydrochlorothiazide-induced functional renal failure.
Non-depolarizing muscle relaxants (e.g. tubocurarine): possible enhancement of the muscle relaxant effect.
Cytotoxic drugs (e.g. cyclophosphamide, methotrexate): thiazides may reduce the renal excretion of cytotoxic drugs and enhance their myelosuppressive effects.
Cholestyramine and colestipol resins: Even with a single dose, cholestyramine or colestipol resins bind hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by 85% and 43%, respectively.
Antigout agents (probenecid, sulfinpyrazone and allopurinol): Dose adjustment of uricosuric agents is necessary, as hydrochlorothiazide may increase serum uric acid levels. An increase in the dose of probenecid or sulfinpyrazone may be necessary. Concomitant use of thiazide diuretics, including hydrochlorothiazide, may increase the frequency of hypersensitivity reactions to allopurinol.
Anticholinergics (e.g., atropine, biperiden): increase the bioavailability of thiazide diuretics, reducing gastrointestinal motility and gastric emptying rate.
Salicylates: In the case of high doses of salicylates, hydrochlorothiazide may enhance their toxic effect on the central nervous system.
Methyldopa: Isolated cases of hemolytic anemia have been reported with concomitant use with hydrochlorothiazide.
Cyclosporine: increased risk of hyperuricemia and gout.
- blockers and diazoxide: their hyperglycemic effect may be increased by thiazides.
Amantadine: Hydrochlorothiazide may increase the risk of adverse reactions to amantadine.
Iodinated contrast media: In case of diuretic-induced dehydration, the risk of acute renal failure increases, especially with high doses of iodine preparations. Rehydration should be performed before use.
Application features
Non-melanoma skin cancer.
An increased risk of non-melanoma skin cancer (NMSC) with increasing cumulative dose of GCS has been found in two pharmacoepidemiological studies. The photosensitizing effect of GCS may be a mechanism for the development of this pathology.
To reduce the risk of skin cancer, patients should be informed about possible preventive measures, such as limiting exposure to sunlight and UV radiation, and in case of exposure, about the need for adequate skin protection. Suspicious skin lesions should be examined as soon as possible, including histological examination of biopsy material.
Patients who have previously had NMSR may also need to reconsider the use of HTZ.
Kidney dysfunction.
Diuretics, including hydrochlorothiazide, should be used with caution in patients with severe renal impairment. Thiazides may cause or accelerate the development of azotemia and exacerbate pre-existing renal impairment. Cumulative effects of the drug are possible. If renal impairment progresses, azotemia significantly increases, and oliguria develops, the diuretic should be discontinued.
Liver dysfunction.
Thiazides should be used with caution in patients with impaired liver function or progressive liver disease, as these drugs can cause intrahepatic cholestasis, and even minor changes in fluid and electrolyte balance or blood ammonia levels can precipitate/accelerate the development of hepatic coma, hepatic encephalopathy, and hepatorenal syndrome. In this case, diuretic treatment should be discontinued.
Hypersensitivity reactions.
It should be borne in mind that they may occur in patients with or without a history of allergic diseases or bronchial asthma. Development or exacerbation of connective tissue diseases, such as systemic lupus erythematosus, has been reported during thiazide therapy.
Choroidal effusion with visual field defect, acute myopia and secondary angle-closure glaucoma.
Hydrochlorothiazide may cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, acute transient myopia and acute angle-closure glaucoma. Symptoms are characterized by an acute onset of decreased visual acuity and/or eye pain and usually develop within a few hours to a few weeks of initiating treatment with hydrochlorothiazide.
Untreated acute angle-closure glaucoma may lead to permanent vision loss. The initial treatment is to discontinue hydrochlorothiazide as soon as possible. Urgent medical or surgical treatment should be considered if intraocular pressure remains uncontrolled. A history of allergy to sulfonamides or penicillin may be a risk factor for the development of acute angle-closure glaucoma.
Acute respiratory toxicity.
Very rare cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS), have been reported following the administration of hydrochlorothiazide. Pulmonary oedema usually develops within minutes to hours of administration. Early symptoms include dyspnoea, fever, worsening pulmonary function and hypotension. If ARDS is suspected, hydrochlorothiazide should be discontinued and appropriate treatment initiated. Hydrochlorothiazide should not be given to patients who have previously experienced ARDS after taking hydrochlorothiazide.
Water and electrolyte balance.
Thiazides should be started only after correction of pre-existing fluid and electrolyte imbalances.
All patients receiving diuretic therapy should be monitored for possible fluid and electrolyte imbalance, including hypovolemia, hyponatremia, hypokalemia, hypomagnesemia, and hypochloremic alkalosis. Potassium, magnesium, sodium, and other blood electrolytes, as well as plasma creatinine clearance, should be monitored regularly during prolonged diuretic therapy.
Determining serum and urine electrolyte levels is especially important when the patient is suffering from excessive vomiting and/or diarrhea or is receiving parenteral fluids.
Serum electrolyte levels may also be affected by concomitant use of drugs such as cardiac glycosides, glucocorticosteroids, and adrenocorticotropic hormone.
Thiazides should be used with caution in diseases accompanied by increased potassium loss. Hypokalemia may increase the toxic effects of cardiac glycosides (e.g., ventricular excitability). Competing magnesium deficiency may complicate correction of hypokalemia. With prolonged use of hydrochlorothiazide, patients are advised to adhere to a diet rich in potassium and/or take potassium supplements.
Dilutional hyponatremia may occur in patients with edema in hot weather; appropriate corrective measures are water restriction rather than salt administration, unless the hyponatremia is life-threatening.
Monitoring of serum electrolytes is particularly indicated in elderly patients, patients with ascites due to cirrhosis of the liver or with edema due to nephrotic syndrome. In nephrotic syndrome, hydrochlorothiazide should only be used under strict supervision in patients with normal blood potassium levels and without signs of hypovolemia or severe hypoalbuminemia.
Arterial hypotension and antihypertensive drugs.
As with other antihypertensive drugs, symptomatic hypotension may occur in some patients. Thiazides may potentiate the effects of other antihypertensive drugs. When used concomitantly with hydrochlorothiazide, a reduction in the dose of the antihypertensive drug may be necessary to prevent excessive hypotension.
The antihypertensive effect of hydrochlorothiazide may be enhanced after sympathectomy.
Ischemic heart disease, cerebrovascular disease, aortic and mitral valve stenosis. The drug should be prescribed with caution due to the possible excessive decrease in blood pressure, which can lead to myocardial infarction or stroke. With particular caution, prescribe to patients with cerebral and coronary atherosclerosis.
Elderly patients.
When prescribing hydrochlorothiazide, it should be borne in mind that patients of this age group may be more sensitive to the drug, so a halved therapeutic dose may be sufficient. It should be borne in mind that in elderly patients, creatinine clearance depends on age, body weight, and gender.
Metabolic and endocrinological effects.
Diuretics, including hydrochlorothiazide, may cause impaired glucose tolerance and hyperglycemia. Dosage adjustments of insulin and oral hypoglycemic agents may be required (see Interactions with other medicinal products and other forms of interaction). Latent diabetes may be manifested during thiazide therapy.
Diuretics may reduce urinary calcium excretion and, as a result, cause a slight transient increase in its level in the blood plasma. Significant hypercalcemia may be a manifestation of latent hyperparathyroidism. Pathological changes in the parathyroid glands with hypercalcemia and hypophosphatemia have been observed in some patients during long-term thiazide therapy. Thiazides should be discontinued before testing parathyroid function.
When using hydrochlorothiazide, the concentration of free bilirubin in the blood serum may increase (due to displacement from albumin binding). It is possible to increase the level of cholesterol, LDL and triglycerides.
Thiazides may reduce the level of protein-bound iodine in the blood plasma without signs of thyroid dysfunction.
In some patients, thiazide therapy may cause hyperuricemia and worsen/precipitate gout attacks in predisposed patients.
False-positive anti-doping test results are possible when using hydrochlorothiazide.
The drug contains lactose, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not use the drug.
Use during pregnancy or breastfeeding
Hydrochlorothiazide should only be administered during pregnancy after assessing the benefit/risk ratio for the mother, as the drug reduces maternal plasma volume, uteroplacental blood flow, and crosses the placental barrier. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and other adverse effects.
Since hydrochlorothiazide passes into breast milk, breastfeeding should be discontinued if necessary.
Ability to influence reaction speed when driving vehicles or other mechanisms
Until the individual reaction to the drug is determined, one should refrain from driving or operating other mechanisms, considering that during treatment, the ability to concentrate and speed of psychomotor reactions may decrease, dizziness may occur, and vision may be impaired.
Method of administration and doses
The dose of hydrochlorothiazide is determined by the doctor individually. The tablets should be taken after meals.
Due to increased excretion of potassium and magnesium during treatment, replacement therapy with potassium (K+ < 3.0 mmol/l) and magnesium may be necessary.
In edematous syndrome, the initial dose is 25-75 mg (depending on clinical efficacy) once a day or once every 2 days. The maximum daily dose is 100 mg.
As an antihypertensive agent, Hydrochlorothiazide should be prescribed at an initial daily dose of 25-50 mg per dose as monotherapy or in combination with other antihypertensive drugs.
In some cases, an initial dose of 12.5* mg is effective. If necessary, the dose can be increased, but the maximum daily dose should not exceed 100 mg per day.
*If it is necessary to use hydrochlorothiazide at a dose of 12.5 mg, a drug with the possibility of such a dosage should be used.
The hypotensive effect of hydrochlorothiazide is manifested within 3-4 days, but it may take up to 3-4 weeks to achieve the optimal effect. After the end of treatment, the hypotensive effect persists for about 1 week.
For premenstrual edema, the usual dose is 25 mg per day, which should be used from the onset of symptoms until the onset of menstruation.
In nephrogenic diabetes insipidus, the average therapeutic dose is 50 mg per day. If necessary, the dose can be increased to 100 mg per day.
To reduce intraocular pressure in glaucoma, prescribe 25 mg once every 1-6 days; the effect occurs after 24-48 hours.
The daily dose of the drug for children aged 2 years and older is 1-2 mg/kg of body weight. Depending on the body weight for children from 2 to 12 years old - 37.5-100 mg per day. The frequency of administration is 1-2 times a day.
Children.
Use for children over 2 years of age.
Overdose
Symptoms: dehydration, hypokalemia, hyponatremia, hypochloremia. As a result, the following occur: thirst, nausea, vomiting, tachycardia, fatigue, weakness, dizziness, impaired consciousness, arterial hypotension, bradycardia, cardiac arrhythmias, spasms/convulsions of the calf muscles, paresthesias, polyuria, oliguria or anuria, shock, alkalosis, increased blood urea nitrogen (especially in patients with renal failure).
Treatment: symptomatic and supportive therapy, there is no specific antidote. Gastric lavage and the use of activated charcoal are recommended to reduce the absorption of the drug. In case of arterial hypotension, the patient should be placed in a horizontal position with the legs raised. Fluid volume should be compensated and electrolyte imbalance should be normalized (in case of arterial hypotension or shock). If necessary, provide oxygen access or perform artificial respiration. Water and electrolyte balance (especially serum potassium) and laboratory indicators of kidney function should be monitored until they normalize.
Side effects
Blood and lymphatic system: leukopenia, neutropenia/agranulocytosis, thrombocytopenia with/without purpura, hemolytic and aplastic anemia, decreased hematocrit, myelosuppression, lymphadenopathy.
Immune system: hypersensitivity reactions, including anaphylactic reactions, anaphylactic shock, angioedema (including swelling of the face, lips, tongue, larynx, extremities, intestinal edema).
Metabolic disorders: hyperuricemia, which can provoke gout attacks in patients with asymptomatic disease, electrolyte imbalance, including hyponatremia and hypokalemia, hypomagnesemia, hypercalcemia, increased blood lipid levels; gout, hyperglycemia, glucosuria, impaired glucose tolerance, which can lead to the manifestation of latent diabetes mellitus, hypochloremic alkalosis; increased levels of urea and creatinine, liver enzymes and bilirubin, cholesterol, triglycerides in blood plasma.
Mental disorders: anxiety, depression, sleep disturbances, confusion, disorientation, drowsiness, mood and mental changes, nervousness.
Nervous system: dizziness, headache, paresthesia, convulsions, unusual fatigue and weakness, apathy, slowing of the thinking process, fainting, asthenia.
Organs of vision: blurred vision, xanthopsia, conjunctivitis, acute myopia and secondary acute angle-closure glaucoma, choroidal effusion.
Hearing and balance disorders: vertigo, tinnitus.
Cardiovascular system: arrhythmias, orthostatic hypotension, arterial hypotension, tachycardia.
Respiratory, thoracic and mediastinal disorders: acute respiratory distress syndrome (ARDS), including pneumonitis and pulmonary oedema (see section "Special warnings and precautions for use").
Digestive system: anorexia, nausea, vomiting, diarrhea, constipation, dry mouth, increased thirst, stomatitis/aphthous ulcers, glossitis, change in taste, epigastric pain/spasm, pancreatitis.
Hepatobiliary system: development of hepatic encephalopathy or hepatic coma, hepatocellular or cholestatic jaundice, cholecystitis.
Skin and subcutaneous tissue: skin rash, photosensitivity, pruritus, urticaria, purpura, erythroderma, necrotizing vasculitis, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, toxic epidermal necrolysis, cutaneous lupus-like reactions, alopecia.
Musculoskeletal: cramps or muscle pain.
Urinary system: renal dysfunction, interstitial nephritis, renal failure.
Neoplasm: non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) (see sections "Pharmacodynamics" and "Special instructions").
Others: decreased potency/impotence, increased body temperature, sialadenitis.
Expiration date
5 years.
Storage conditions
In the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister, 2 blisters in a pack; 20 tablets in a blister.
Vacation category
According to the recipe.
Producer
Public Joint Stock Company "Research and Production Center "Borshchagov Chemical and Pharmaceutical Plant". Limited Liability Company "Agropharm".
Location of the manufacturer and address of its place of business.
Ukraine, 03134, Kyiv, Myru St., 17.
Ukraine, 08200, Kyiv region, Irpin city, Centralna st., 113-A.
