Ordiss N tablet 12.5mg+16mg cor x30 175978

Ordiss N

Ordiss N tablet 12.5mg+16mg x30, ATX code: C09DA06 (Candesartan in combination with diuretics)

Active substances

hydrochlorothiazide Rec.INN WHO registered candesartan Rec.INN WHO registered

Dosage forms

Ordiss N®

Tabletkireg. No.: LP-002097 from 06/10/13 - Indefinitely Re-registration date: 08/03/18

Release form, packaging and composition of Ordiss N®

The tablets are light pink, biconvex, capsule-shaped, with a score line on both sides, engraved “C” on one side and “16” on opposite sides.

1 tab.

candesartan cilexetil 16 mg

hydrochlorothiazide 12.5 mg

Excipients: pregelatinized starch - 15 mg, povidone-K30 - 16 mg, calcium carmellose - 6.6 mg, poloxamer 188 - 1 mg, microcrystalline cellulose - 72 mg, lactose monohydrate - 177.6 mg, red iron oxide dye (E172) - 0.1 mg , magnesium stearate - 3.2 mg.

The tablets are white or almost white, biconvex, capsule-shaped, with a score on both sides, engraved “C” on one side and “32” on opposite sides.

1 tab.

candesartan cilexetil 32 mg

hydrochlorothiazide 12.5 mg

Excipients: pregelatinized starch - 30 mg, povidone-K30 - 32 mg, calcium carmellose - 13.2 mg, poloxamer 188 - 2 mg, microcrystalline cellulose - 148 mg, lactose monohydrate - 363.9 mg, magnesium stearate - 6.4 mg.

The tablets are light pink, biconvex, capsule-shaped, with a line on both sides, on one side there is an engraving of “H” and “25” on opposite sides of the lines, on the other side there is an engraving of “C” and “32” on opposite sides of the lines.

1 tab.

candesartan cilexetil 32 mg

hydrochlorothiazide 25 mg

Excipients: pregelatinized starch - 30 mg, povidone-K30 - 32 mg, calcium carmellose - 13.2 mg, poloxamer 188 - 2 mg, microcrystalline cellulose - 144 mg, lactose monohydrate - 355.2 mg, iron dye red oxide (E172) - 0.2 mg , magnesium stearate - 6.4 mg.

Clinical and pharmacological group: Combined antihypertensive drug. Angiotensin II receptor antagonist + diuretic Pharmacotherapeutic group: Antihypertensive combined drug (angiotensin II receptor blocker + diuretic)

pharmachologic effect

Angiotensin II is the main hormone of the RAAS, which plays an important role in the pathogenesis of arterial hypertension, heart failure and other cardiovascular diseases. The main physiological effects of angiotensin II are vasoconstriction, stimulation of aldosterone production, regulation of fluid and electrolyte status, and stimulation of cell growth. The effects are mediated by the interaction of angiotensin II with angiotensin type 1 receptors (AT1 receptors).

Candesartan is a selective antagonist of AT1 receptors of angiotensin II, does not inhibit ACE, which converts angiotensin I into angiotensin II, destroying bradykinin, does not lead to the accumulation of bradykinin or substance P. As a result of blocking the AT1 receptors of angiotensin II, a dose-dependent increase in the content of renin and angiotensin I occurs , angiotensin II and a decrease in the concentration of aldosterone in the blood plasma.

When comparing candesartan with ACE inhibitors, the development of cough was less common in patients receiving candesartan.

Candesartan does not bind to the receptors of other hormones and does not block ion channels involved in the regulation of the functions of the cardiovascular system.

Hydrochlorothiazide is a thiazide diuretic that inhibits active sodium reabsorption, mainly in the distal renal tubules and increases the excretion of sodium, chlorine and water ions. The excretion of potassium and magnesium by the kidneys increases in a dose-dependent manner, while calcium begins to be reabsorbed in greater quantities than before.

Hydrochlorothiazide reduces the volume of blood plasma and extracellular fluid, reduces the intensity of blood transport by the heart, and lowers blood pressure. During long-term treatment, the hypotensive effect develops due to the dilation of arterioles. Long-term use of hydrochlorothiazide reduces the risk of cardiovascular disease and mortality.

Candesartan and hydrochlorothiazide have a cumulative hypotensive effect. In patients with arterial hypertension, the use of candesartan/hydrochlorothiazide causes an effective and lasting reduction in blood pressure without increasing heart rate. Orthostatic arterial hypotension is not observed when taking the drug for the first time; after treatment, arterial hypertension does not increase.

After a single dose of candesartan/hydrochlorothiazide, the main hypotensive effect develops within 2 hours. The use of the drug once a day effectively and gently reduces blood pressure within 24 hours with a slight difference between the maximum and average effect of action. With long-term treatment, a stable decrease in blood pressure occurs within 4 weeks after starting the drug and can be maintained with a long course of treatment.

In clinical studies, the incidence of side effects, especially cough, was lower with candesartan/hydrochlorothiazide than with a combination of ACE inhibitors and hydrochlorothiazide.

There are currently no data on the use of candesartan/hydrochlorothiazide in patients with renal failure, nephropathy, reduced left ventricular function, acute heart failure and myocardial infarction.

The effectiveness of candesartan/hydrochlorothiazide does not depend on gender or age.

Pharmacokinetics

Suction and distribution

Candesartan. When candesartan is absorbed from the gastrointestinal tract, cilexitil quickly turns into the active substance, candesartan, through ether hydrolysis, binds strongly to AT1 receptors and slowly dissociates, and has no agonist properties. The absolute bioavailability of candesartan after oral administration is about 40%. The relative bioavailability of the tablet form compared to the oral solution is approximately 34%. Thus, the calculated absolute bioavailability of the tablet form of the drug is 14%. Food intake does not have a significant effect on AUC, i.e. food does not significantly affect the bioavailability of the drug.

Cmax in blood plasma is achieved 3-4 hours after taking the tablet form of the drug. As the dose increases within the recommended limits, the concentration of candesartan increases linearly. The binding of candesartan to plasma proteins is more than 99%. Plasma Vd of candesartan is 0.1 l/kg.

The pharmacokinetic parameters of candesartan do not depend on the gender of the patient.

Hydrochlorothiazide. Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract. Bioavailability is approximately 70%. Concomitant meals increase absorption by approximately 15%. Bioavailability may be reduced in patients with heart failure and severe edema.

Plasma protein binding is approximately 60%. Apparent Vd is approximately 0.8 l/kg.

Metabolism and excretion

Candesartan. Candesartan is mainly excreted unchanged from the body by the kidneys and through the intestines with bile and is only slightly metabolized in the liver. T1/2 is approximately 9 hours. Cumulation of candesartan in the body is not observed.

The total clearance of candesartan is about 0.37 ml/min/kg, while the renal clearance is about 0.19 ml/min/kg. Renal excretion of candesartan is carried out by glomerular filtration and active tubular secretion.

When radiolabeled candesartan is administered orally, approximately 26% of the administered amount is excreted in the urine as candesartan and 7% as an inactive metabolite, whereas 56% of the administered amount is found in the feces as candesartan and 10% as an inactive metabolite.

Hydrochlorothiazide. Hydrochlorothiazide is not metabolized and is excreted almost entirely as the active form of the drug by glomerular filtration and active tubular secretion in the proximal nephron. T1/2 is about 8 hours and does not change when taken together with candesartan. Approximately 70% of the dose taken orally is excreted by the kidneys within 48 hours. When using a combination of drugs, no additional accumulation of hydrochlorothiazide was detected in comparison with monotherapy.

Pharmacokinetics in special clinical situations

Candesartan. In patients over 65 years of age, the Cmax and AUC of candesartan increase by 50% and 80%, respectively, compared with younger patients. However, the hypotensive effect and the incidence of side effects when using candesartan/hydrochlorothiazide do not depend on the age of the patients.

In patients with mild and moderate renal impairment, Cmax and AUC of candesartan increased by 50% and 70%, respectively, while T1/2 did not change compared to patients with normal renal function.

In patients with severe renal impairment and/or those on hemodialysis, the Cmax and AUC of candesartan increased by 50% and 110%, respectively, and T1/2 increased by 2 times.

In patients with mild to moderate hepatic impairment, the AUC of candesartan increased by 23%.

Hydrochlorothiazide. T1/2 is longer in patients with renal failure.

Indications for the drug Ordiss N® are the treatment of arterial hypertension in patients who are indicated for combination therapy. ICD-10 codes

Dosage regimen

Ordiss N® should be taken orally 1 time/day, regardless of meals.

The recommended dose is 1 tablet 1 time/day.

It is recommended to titrate the dose of candesartan before transferring the patient from hydrochlorothiazide monotherapy to therapy with Ordiss N®. If necessary, patients are transferred from monotherapy with Ordiss® to therapy with Ordiss N®.

The main hypotensive effect is achieved, as a rule, in the first 4 weeks after the start of treatment.

In elderly patients, no dose adjustment is required.

In patients with mild or moderate renal impairment (creatinine clearance 30-80 ml/min/1.73 m2 body surface area), dose titration is recommended. The drug Ordiss N® is contraindicated in patients with severe renal failure (creatinine clearance <.30 ml/min/1.73 m2 body surface area).

In patients with mild or moderate hepatic impairment, dose titration is recommended. Ordiss N® is contraindicated in patients with severe liver dysfunction and/or cholestasis.

Patients with reduced blood volume: for patients at risk of arterial hypotension, for example, for patients with reduced blood volume, it is recommended to titrate the dose of candesartan (via monotherapy with Ordiss®), starting from 4 mg.

The safety and effectiveness of the drug Ordiss N® in children and adolescents under 18 years of age have not been established.

Side effect

Determination of the frequency of side effects according to WHO recommendations: very often - at least 10%, often - at least 1%, but less than 10%, infrequently - at least 0.1%, but less than 1%, rarely - at least 0.01%, but less 0.1%, very rarely (including individual messages) - less than 0.01%.

Candesartan

From the hematopoietic system: very rarely - leukopenia, neutropenia, agranulocytosis.

Metabolic disorders: very rarely - hyperkalemia, hyponatremia.

From the nervous system: often - dizziness, very rarely - headache.

From the digestive system: very rarely - nausea.

From the liver and biliary tract: very rarely - increased activity of liver transaminases, impaired liver function, hepatitis.

From the respiratory system: very rarely - cough.

From the skin and subcutaneous tissues: very rarely - skin rash, itching, urticaria, angioedema.

From the musculoskeletal system: very rarely - back pain, arthralgia, myalgia.

From the kidneys and urinary tract: very rarely - renal failure (see section "Special instructions").

Hydrochlorothiazide

From the blood system: rarely - leukopenia, neutropenia, agranulocytosis, thrombocytopenia, aplastic anemia, suppression of bone marrow function, hemolytic anemia, decreased hemoglobin.

From the immune system: rarely - anaphylactic reaction.

Metabolism: often - hyperglycemia, hyperuricemia, hyponatremia, hypokalemia.

From the nervous system: often - dizziness, vergigo, rarely - sleep disturbances, anxiety, depression, paresthesia.

From the organ of vision: rarely - decreased clarity of vision, acute myopia, acute angle-closure glaucoma.

From the cardiovascular system: infrequently - postural hypotension, rarely - arrhythmia, vasculitis.

From the respiratory system: rarely - respiratory distress syndrome, pneumonitis, pulmonary edema.

From the digestive system: infrequently - anorexia, loss of appetite, constipation, diarrhea, irritation of the gastric mucosa, rarely - pancreatitis.

From the liver and biliary tract: rarely - intrahepatic cholestatic jaundice.

From the skin and subcutaneous tissues: infrequently - rash, urticaria, photosensitivity reaction, rarely - toxic epidermal necrolysis, erythematous-like reactions, relapse of cutaneous erythematosis.

From the musculoskeletal system: rarely - muscle spasm.

From the urinary system: often - glucosuria, rarely - renal dysfunction, interstitial nephritis.

Other: often - weakness, increased concentrations of cholesterol, triglycerides in the blood plasma, rarely - fever, increased concentrations of creatinine, urea in the blood plasma.

Contraindications for use

hypersensitivity to candesartan, hydrochlorothiazide and other components of the drug, hypersensitivity to other sulfonamide derivatives, primary hyperaldosteronism, gout, severe renal dysfunction (GFR <.30 ml/min/1.73 m2), severe liver dysfunction, cholestasis, refractory hypokalemia, hypercalcemia, condition after kidney transplantation, pregnancy, breastfeeding, childhood and adolescence under 18 years of age, simultaneous use with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and/or impaired renal function (GFR <.60 ml/min/1.73 m2 ), lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

With caution: simultaneous use with other antihypertensive drugs, potassium-sparing diuretics, amphotericin, carbenoxolone, sodium penicillin G drugs, salicylic acid derivatives, cardiac glycosides, antiarrhythmic drugs, lithium drugs, NSAIDs, colestipol, cholestyramine, tubocurarine, beta-blockers, anticholinergic drugs, amantadine, cytotoxic drugs, corticosteroids, ACTH, barbiturates, general anesthetics, epinephrine, iodine-containing drugs, alcohol, impaired renal function (creatinine clearance>30 ml/min), liver failure, severe chronic failure, bilateral renal artery stenosis, single artery stenosis kidneys, hemodynamically significant stenosis of the aortic and/or mitral valve, coronary heart disease, hypertrophic obstructive cardiomyopathy, decreased blood volume, diabetes mellitus, cerebrovascular diseases, acute myopia, angle-closure glaucoma, systemic lupus erythematosus, simultaneous use with alcohol.

Use during pregnancy and breastfeeding

The drug Ordiss N® is contraindicated for use during pregnancy and breastfeeding.

Patients taking the drug should be warned about this before planning pregnancy so that they can switch to alternative therapy with a proven safety profile for use during pregnancy. If pregnancy is diagnosed, drug therapy should be stopped immediately. Drugs that affect the RAAS can cause developmental disorders in the fetus and/or have a negative effect on the newborn, including death when using the drug during pregnancy. It is known that therapy with angiotensin II receptor antagonists can cause developmental disorders of the fetus (impaired renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (impaired renal function, arterial hypotension, hyperkalemia).

Experience with the use of hydrochlorothiazide during pregnancy is limited. Hydrochlorothiazide penetrates the placental barrier. Given the mechanism of action of hydrochlorothiazide, its use during pregnancy can cause disturbances in fetoplacental circulation and undesirable effects in the fetus and newborn in the form of jaundice, water-electrolyte imbalance and thrombocytopenia.

It is not known whether candesartan is excreted into breast milk in humans. Candesartan is excreted in the milk of lactating rats. Hydrochlorothiazide is excreted in breast milk.

Use for liver dysfunction

The drug Ordiss N is contraindicated in patients with severe liver failure. Use with caution in cases of moderate renal failure.

Use for impaired renal function Ordiss N is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min). Use with caution in cases of moderate renal failure.

Use in children The safety and effectiveness of Ordiss N® in children and adolescents under 18 years of age have not been established.

Use in elderly patients No dose adjustment is required in elderly patients.

special instructions

Concomitant use of ACE inhibitors, ARB II or aliskiren increases the risk of developing arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure). Double blockade of the RAAS when using ACE inhibitors, ARB II or aliskiren is not recommended (see section “Drug Interactions”).

If double blockade of the RAAS is considered absolutely necessary, then treatment should be carried out only under the supervision of a physician and with regular monitoring of renal function, electrolyte levels and blood pressure. ACE inhibitors and ARB II should not be used simultaneously in patients with diabetic nephropathy.

There are no data on the use of Ordiss N® in patients who have recently undergone a kidney transplant.

Drugs that affect the RAAS (eg, ACE inhibitors) may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or arterial stenosis of a solitary kidney. A similar effect should be expected from angiotensin II receptor antagonists.

In patients with BCC and/or sodium deficiency, symptomatic arterial hypotension may develop, so it is not recommended to use the drug Ordiss N® until these symptoms disappear.

In patients receiving angiotensin II antagonists, hypotension may develop during anesthesia and during surgery as a result of blockade of the RAAS. Very rarely, cases of severe arterial hypotension may occur, requiring IV fluids and/or vasoconstrictors.

Patients with impaired liver function or progressive liver disease should use thiazide diuretics with caution, because Minor fluctuations in fluid volume and electrolyte composition can cause hepatic coma. There are no data on the use of Ordiss N® in patients with liver failure.

When prescribing Ordiss N® to patients with obstructive hypertrophic cardiomyopathy or hemodynamically significant stenosis of the aortic or mitral valve, caution should be exercised.

Patients with primary hyperaldosteronism are usually resistant to treatment with antihypertensive drugs that affect the RAAS, therefore, the use of Ordiss N® in such patients is not recommended.

As in all cases of taking drugs that have a diuretic effect, electrolytes in the blood plasma should be monitored.

Thiazide-based drugs that have a diuretic effect can reduce the excretion of calcium ions in the urine and can cause sudden changes and a slight increase in the concentration of calcium ions in the blood plasma.

Thiazides, incl. and hydrochlorothiazide, can cause disturbances in water-salt balance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia and hypochloremic alkalosis).

Detected hypercalcemia may be a sign of latent hyperparathyroidism.

The use of thiazide diuretics should be discontinued until results of parathyroid tests are available.

Hydrochlorothiazide increases potassium excretion in a dose-dependent manner, which may cause hypokalemia. This effect of hydrochlorothiazide is less pronounced if it is used simultaneously with candesartan. The risk of hypokalemia appears to be increased in patients with liver cirrhosis, increased diuresis, taking fluids with a reduced salt content, and undergoing concurrent treatment with corticosteroids or ACTH.

Based on experience with the use of drugs that affect the RAAS, the concurrent use of Ordiss N® and diuretics that increase potassium excretion can be compensated by the use of nutritional supplements containing potassium or other drugs that can increase the level of potassium in the blood plasma.

The use of Ordiss N® may cause hypokalemia, especially in patients with heart or renal failure (such cases have not been documented).

Thiazide diuretics increase magnesium excretion, which can cause hypomagnesemia.

The use of thiazide diuretics can change the concentration of glucose in the blood up to the manifestation of latent diabetes mellitus. Dosage adjustment of hypoglycemic agents, including insulin, may be required.

The use of thiazide diuretics is associated with an increase in cholesterol and triglycerides in the blood plasma. However, when using the drug Ordiss N®, a minimal amount or absence of such effects was observed.

Thiazide diuretics increase plasma uric acid concentrations and may precipitate gout in predisposed patients.

Patients whose vascular tone and renal function are predominantly dependent on the activity of the RAAS (for example, patients with severe chronic heart failure, kidney disease, including renal artery stenosis) are especially sensitive to drugs acting on the RAAS. The prescription of such drugs is accompanied in these patients by severe arterial hypotension, azotemia, oliguria and, less commonly, acute renal failure. The possibility of developing the listed effects cannot be excluded when using angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with ischemic cardiopathy, cerebrovascular diseases of ischemic origin when using any antihypertensive drugs can lead to the development of myocardial infarction or stroke.

The occurrence of hypersensitivity reactions to hydrochlorothiazide is most likely in patients with bronchial asthma, a history of allergic reactions, which does not exclude the appearance of allergic symptoms in other patients.

When using thiazide diuretics, there have been cases of exacerbation or the appearance of symptoms of congestive seborrhea.

When using thiazide diuretics, there have been cases of worsening of systemic lupus erythematosus.

Hydrochlorothiazide may cause an idiosyncratic reaction leading to the development of acute myopia and secondary angle-closure glaucoma. Symptoms include: sudden loss of vision or eye pain, usually occurring within hours to weeks of starting hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to permanent vision loss. Treatment is to stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, emergency medical treatment or surgery may be required. Risk factors for the development of acute angle-closure glaucoma are a history of an allergic reaction to sulfonamides or benzylpenicillins.

The drug contains lactose, so it should not be taken by patients with rare hereditary diseases manifested by lactose intolerance, lactose deficiency or impaired absorption of glucose and galactose.

Hydrochlorothiazide, which is part of the drug Ordiss N®, can give a positive result during doping control.

Use in pediatrics

The safety and effectiveness of the drug Ordiss N® in children and adolescents under 18 years of age have not been established.

Impact on the ability to drive vehicles and machinery

If undesirable effects from the central nervous system occur during therapy with Ordiss N®, caution should be exercised when performing actions that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: analysis of the pharmacological properties of the drug suggests that the main pro

Ordiss N® (Ordiss N®)

Concomitant use of ACE inhibitors, ARB II or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure). Dual blockade of the RAAS with concomitant use of ACE inhibitors, ARB II or aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in others patients (see section “Interaction with other drugs”).

If double blockade of the RAAS is considered absolutely necessary, then treatment should only occur under the supervision of a physician and should be accompanied by regular monitoring of renal function, electrolytes and blood pressure. The concomitant use of ACE inhibitors and ARB II in patients with diabetic nephropathy is contraindicated and is not recommended in other patients.

In patients with renal failure, the use of loop diuretics is preferable to thiazide diuretics. For patients with renal failure during therapy with Ordiss N®, it is recommended to regularly monitor potassium levels, creatinine and uric acid concentrations. There are no data on the use of Ordiss N® in patients who have recently undergone a kidney transplant.

Drugs that affect the RAAS (eg, ACE inhibitors) may increase blood urea and serum creatinine concentrations in patients with bilateral renal artery stenosis or solitary renal artery stenosis. A similar effect should be expected from angiotensin II receptor antagonists.

In patients with BCC and/or sodium deficiency, symptomatic arterial hypotension may develop, so it is not recommended to use the drug Ordiss N® until these symptoms disappear.

In patients receiving angiotensin II receptor antagonists, hypotension may develop during general anesthesia and during surgery as a result of blockade of the RAAS. Very rarely, cases of severe arterial hypotension may occur, requiring IV fluids and/or vasoconstrictors.

Patients with impaired liver function or progressive liver disease should use thiazide diuretics with caution because minor fluctuations in fluid volume and fluid and electrolyte balance can cause hepatic coma.

There are no data on the use of Ordiss N® in patients with severe liver failure.

When prescribing Ordiss N® to patients with hypertrophic obstructive cardiomyopathy or hemodynamically significant stenosis of the aortic or mitral valve, caution should be exercised. Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that affect the RAAS, therefore the use of Ordiss N® in such patients is not recommended.

As in all cases of taking drugs that have a diuretic effect, the content of electrolytes in the blood plasma should be monitored.

Thiazide-based drugs that have a diuretic effect can reduce the excretion of calcium by the kidneys and can cause sudden changes and a slight increase in calcium levels in the blood plasma.

Thiazides, incl. and hydrochlorothiazide, can cause disturbances in water and electrolyte balance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia and hypochloremic alkalosis).

Detected hypercalcemia may be a sign of latent hyperparathyroidism.

The use of thiazide diuretics should be discontinued until results of parathyroid gland tests are available. Hydrochlorothiazide increases potassium excretion in a dose-dependent manner, which may cause hypokalemia. This effect of hydrochlorothiazide is less pronounced if it is used simultaneously with candesartan. The risk of hypokalemia appears to be increased in patients with liver cirrhosis, increased diuresis, taking fluids with a reduced salt content, and undergoing concurrent treatment with corticosteroids or ACTH.

Based on experience with the use of drugs that affect the RAAS, the simultaneous use of Ordiss N® and diuretics that increase potassium excretion can be compensated by the use of nutritional supplements containing potassium or other drugs that can increase the content of potassium in the blood plasma.

The use of Ordiss N® may cause hypokalemia, especially in patients with heart or renal failure (such cases have not been documented).

Thiazide diuretics increase magnesium excretion, which can cause hypomagnesemia. The use of thiazide diuretics can change the concentration of glucose in the blood up to the manifestation of latent diabetes mellitus. Dosage adjustment of hypoglycemic agents, including insulin, may be required.

Increases in plasma cholesterol and triglyceride concentrations are associated with the use of thiazide diuretics. However, when using the drug Ordiss N®, a minimal amount or absence of such effects was observed.

Thiazide diuretics increase plasma uric acid concentrations and may contribute to the development of gout symptoms in predisposed patients.

A sharp decrease in blood pressure in patients with ischemic cardiopathy, cerebrovascular diseases of ischemic origin when using any antihypertensive drugs can lead to the development of myocardial infarction or stroke.

When using thiazide diuretics, there have been cases of exacerbation or the appearance of symptoms of congestive seborrhea.

When using thiazide diuretics, there have been cases of worsening of systemic lupus erythematosus.

Non-melanoma skin cancer

Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide use and an increased risk of non-melanoma skin cancer (NMSC) basal cell carcinoma and squamous cell carcinoma. The risk of developing NMSC increased with increasing total (cumulative) dose of hydrochlorothiazide. A possible mechanism for the development of NMSC is the photosensitizing effect of hydrochlorothiazide.

Patients taking hydrochlorothiazide as monotherapy or in combination with other drugs should be aware of the risk of developing NMSC. In such patients, it is recommended that the skin be examined to identify any new suspicious lesions, as well as changes in existing skin lesions.

Any suspicious skin changes should be reported to your doctor immediately. Suspicious areas of skin should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.

To minimize the risk of developing NMSC, patients should be advised to follow preventive measures, such as limiting exposure to sunlight and UV rays, and using appropriate protective equipment.

In patients with a history of non-melanoma skin cancer, it is recommended to reconsider the use of hydrochlorothiazide. The drug contains lactose, so it should not be taken by patients with rare hereditary diseases manifested by lactose intolerance, lactase deficiency or impaired absorption of glucose and galactose.

Hydrochlorothiazide, which is part of the drug Ordiss N®, can give a positive result during doping control.

Use in pediatrics

The safety and effectiveness of the drug Ordiss N® in children under 18 years of age have not been established.