Olsapres h

Concomitant use not recommended

Lithium preparations.

Concomitant use of lithium with angiotensin-converting enzyme inhibitors and sometimes with angiotensin II receptor antagonists has been associated with reversible increases in serum lithium concentration and its toxic effects. Moreover, thiazides reduce renal clearance of lithium, thereby increasing the risk of lithium toxicity when used with hydrochlorothiazide. Therefore, concomitant use of Olspres N with lithium is not recommended. In patients who require simultaneous administration of these agents, serum lithium concentrations should be closely monitored during treatment.

Concomitant use requiring caution

• Baclofen.* Hypotensive effect may be enhanced.

Non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs (e.g., acetylsalicylic acid (>3 g/day), COX-2 inhibitors, and non-selective NSAIDs) may attenuate the antihypertensive effects of thiazide diuretics and angiotensin II receptor blockers. In some patients with renal impairment (e.g., dehydrated patients or elderly patients with kidney disease), the use of angiotensin II receptor blockers together with cyclooxygenase-inhibiting agents may exacerbate renal dysfunction, including acute renal failure, which is usually reversible. Therefore, these agents should be used concomitantly with caution, especially in elderly patients. Patients should maintain adequate fluid intake. Furthermore, renal function should be monitored carefully after initiation of combined therapy and at regular intervals thereafter.

Concomitant use requiring special attention

Amifostine.

Antihypertensive effect may be enhanced.

Other antihypertensive agents.

The antihypertensive effect of Olspres N may be enhanced when used concomitantly with other agents that lower blood pressure.

Ethanol, barbiturates, narcotic analgesics, and antidepressants.

Orthostatic hypotension may be intensified.

Potential interactions with olmesartan medoxomil.

Concomitant use not recommended

ACE inhibitors, angiotensin II receptor blockers, or aliskiren.

Clinical data indicate that dual blockade of the renin-angiotensin-aldosterone system (RAAS), associated with the combined use of ACE inhibitors and angiotensin II receptor blockers or aliskiren, increases the incidence of adverse events such as hypotension, hyperkalemia, and renal dysfunction (including acute renal failure), compared to monotherapy with a single RAAS-acting agent.

Medicinal products affecting blood potassium concentration.

Based on experience with other agents acting on the renin-angiotensin system, serum potassium concentration may increase when potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other agents capable of increasing serum potassium (e.g., heparin, ACE inhibitors) are used concomitantly. When Olspres N is prescribed together with potassium-affecting agents, serum potassium levels should be monitored.

Medicinal product colesevelam, a bile acid sequestrant.

Concomitant use of the bile acid sequestrant colesevelam hydrochloride reduces systemic exposure and peak plasma concentration of olmesartan, as well as its elimination half-life. Administration of olmesartan medoxomil at least 4 hours before colesevelam hydrochloride reduces the effect of this drug interaction. Consideration should be given to administering olmesartan medoxomil at least 4 hours before colesevelam hydrochloride.

Additional information.

A moderate reduction in the bioavailability of olmesartan medoxomil has been observed after treatment with antacids (magnesium-aluminum hydroxide). Olmesartan medoxomil does not have a significant effect on the pharmacokinetics and pharmacodynamics of warfarin or the pharmacokinetics of digoxin. No clinically significant changes in the pharmacokinetics of either drug were observed when olmesartan medoxomil was co-administered with pravastatin. In vitro studies did not show clinically significant inhibition by olmesartan of the activity of human cytochrome P450 isoenzymes IA1/2, IIA6, IIC8/9, IIC19, IID6, IIE1, and IIIA4; olmesartan either had minimal inductive effects or no effect at all on animal cytochrome P450 isoenzymes. Therefore, clinically significant interactions between olmesartan and medicinal products metabolized by the aforementioned cytochrome P450 isoenzymes are not expected.

Potential interactions with hydrochlorothiazide.

Concomitant use not recommended

Medicinal products affecting blood potassium concentration.

The hypokalemic effect of hydrochlorothiazide may be enhanced when used concomitantly with other medicinal products causing potassium loss and hypokalemia (e.g., potassium-wasting diuretics, laxatives, corticosteroids, ACTH, amphotericin, carbenoxolone, sodium penicillin G, and salicylate derivatives). Therefore, concomitant use of hydrochlorothiazide with these agents is not recommended.

Concomitant use requiring caution

Calcium salts.

Thiazide diuretics may increase serum calcium concentration by reducing calcium excretion. If calcium supplements are necessary, serum calcium levels should be monitored and the calcium dose adjusted accordingly.

Cholestyramine and colestipol.

The use of anion-exchange resins slows the absorption of hydrochlorothiazide.

Cardiac glycosides.

The use of cardiac glycosides increases the risk of arrhythmias in the presence of thiazide-induced hypokalemia and hypomagnesemia.

Medicinal products whose efficacy depends on changes in serum potassium concentration.

When Olspres N is used concomitantly with medicinal products whose efficacy depends on changes in serum potassium concentration (e.g., cardiac glycosides and antiarrhythmic agents), or with agents that may cause torsade de pointes (ventricular tachycardia), including certain antiarrhythmic agents, regular monitoring of serum potassium concentration and ECG is recommended:

• Class Ia antiarrhythmic agents (e.g., quinidine, hydroquinidine, disopyramide);
• Class III antiarrhythmic agents (e.g., amiodarone, sotalol, dofetilide, ibutilide);
• Certain antipsychotics (e.g., thioridazine, chlorpromazine, levomepromazine, trifluoperazine, zuclopenthixol, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol);
• Others (e.g., bepridil, cisapride, difemanil, intravenous erythromycin, halofantrine, mizolastine, pentamidine, sparfloxacin, terfenadine, intravenous vinca alkaloids).

Non-depolarizing skeletal muscle relaxants (e.g., tubocurarine).

Hydrochlorothiazide may enhance the effect of non-depolarizing skeletal muscle relaxants.

Anticholinergic agents (e.g., atropine and biperiden).

By reducing gastrointestinal motility and gastric emptying, anticholinergic agents may increase the bioavailability of thiazide diuretics.

Antidiabetic medicinal products (oral agents and insulin).

Thiazide therapy may affect glucose tolerance. Dose adjustment of antidiabetic agents may be necessary.

Metformin.

Metformin should be used with caution due to the risk of lactic acidosis caused by functional renal impairment, which may occasionally occur with hydrochlorothiazide use.

Beta-blockers and diazoxide.

The hyperglycemic effect of beta-blockers and diazoxide may be enhanced by thiazides.

Pressor amines (e.g., noradrenaline).

The effectiveness of pressor amines may be reduced.

Medicinal products used to treat gout (probenecid, sulfinpyrazone, and allopurinol).

Since hydrochlorothiazide may occasionally increase serum uric acid concentration, dose adjustment of uricosuric agents used to treat gout may be necessary. Additionally, the dose of probenecid or sulfinpyrazone may sometimes need to be increased. When allopurinol is used concomitantly with thiazides, the frequency of allergic reactions to allopurinol may increase.

Amantadine.

Thiazides may increase the risk of adverse reactions caused by amantadine.

Antineoplastic agents (e.g., cyclophosphamide, methotrexate).

Thiazides may reduce renal excretion of anticancer drugs and enhance their myelosuppressive effects.

Salicylates.

When high doses of salicylates are administered, hydrochlorothiazide may potentiate their toxic effects on the central nervous system.

Metildopa.

Published reports describe isolated cases of hemolytic anemia associated with the use of hydrochlorothiazide in combination with methyldopa.

Cyclosporine.

Concomitant use of thiazides with cyclosporine may increase the risk of hyperuricemia and complications similar to gout.

Tetracycline.

Concomitant use of thiazides with tetracycline increases the risk of tetracycline-induced uremia. This effect probably does not apply to doxycycline.

Carbamazepine.

Due to the risk of symptomatic hyponatremia, clinical and biological monitoring is required.

Iodinated contrast agents.

Diuretics may lead to patient dehydration; therefore, adequate hydration should be ensured before administering high doses of iodinated contrast agents to reduce the risk of acute renal failure.

Special precautions for use.

Reduction in circulating blood volume.

In patients with reduced circulating blood volume and/or low sodium levels due to intensive diuretic therapy, low-salt diet, diarrhea, or vomiting, clinically significant arterial hypotension may occur, especially after the first dose of the drug. Before initiating treatment with Olspres N, these conditions should be corrected.

Other conditions associated with activation of the renin-angiotensin-aldosterone system (RAAS).

Patients in whom vascular tone and renal function are highly dependent on RAAS activity (e.g., those with severe congestive heart failure or renal disease, including renal artery stenosis) may experience acute arterial hypotension, azotemia, oliguria, or, in rare cases, acute renal failure when treated with drugs affecting this system.

Renovascular hypertension.

The use of drugs affecting the RAAS in patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney is associated with an increased risk of severe arterial hypotension and renal failure.

Renal impairment and kidney transplantation.

Olspres N is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min) (see section "Contraindications"). Dose adjustment is not required in patients with mild to moderate renal impairment (creatinine clearance ≥30 mL/min but <60 mL/min). However, the drug should be used with caution in such patients, and periodic monitoring of serum potassium, creatinine, and uric acid concentrations is recommended. Azotemia due to thiazide diuretics may occur in patients with renal impairment. If progressive renal failure becomes evident, the treatment regimen should be carefully reviewed and diuretics discontinued if necessary. There is no clinical experience with the use of Olspres N in patients who have recently undergone kidney transplantation.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS).

Concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of arterial hypotension, hyperkalemia, and impaired renal function (including acute renal failure). Therefore, dual RAAS blockade with concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended.

If dual blockade therapy is absolutely necessary, it should be administered only under specialist supervision and with close monitoring of renal function, electrolyte levels, and blood pressure.

Patients with diabetic nephropathy should not receive concomitant treatment with ACE inhibitors and angiotensin II receptor blockers.

Hepatic impairment.

There is no experience with the use of olmesartan medoxomil in patients with severe hepatic impairment. Additionally, minor disturbances in fluid and electrolyte balance caused by thiazide therapy may precipitate hepatic coma in patients with hepatic impairment or progressive liver disease. Therefore, Olspres N should be used with caution in patients with mild to moderate hepatic impairment. Olspres N is contraindicated in patients with severe hepatic impairment, cholestasis, or biliary obstruction.

Aortic valve stenosis and mitral valve stenosis, hypertrophic obstructive cardiomyopathy.

As with other vasodilators, olmesartan medoxomil should be used with caution in patients with aortic valve stenosis or mitral valve stenosis, as well as in those with obstructive hypertrophic cardiomyopathy.

Primary hyperaldosteronism.

Patients with primary hyperaldosteronism generally do not respond to antihypertensive agents that suppress the renin-angiotensin system. Therefore, Olspres N is not recommended for such patients.

Metabolic and endocrine effects.

Thiazide drugs may impair glucose tolerance. Insulin or oral hypoglycemic agents may require dose adjustment in diabetic patients. Thiazide use may also unmask latent diabetes mellitus.

Thiazide diuretics may cause increases in serum cholesterol and triglyceride levels. In some cases, thiazide use may lead to hyperuricemia or gout. Hydrochlorothiazide may increase serum free bilirubin levels.

Hydrochlorothiazide

Acute respiratory toxicity.

Very rare, severe cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS), have been reported after hydrochlorothiazide administration. Pulmonary edema usually develops within minutes or hours after taking hydrochlorothiazide. Initial symptoms include dyspnea, fever, worsening pulmonary condition, and hypotension. If ARDS is suspected, hydrochlorothiazide should be discontinued immediately and appropriate treatment initiated. Hydrochlorothiazide should not be prescribed to patients who previously experienced ARDS after taking hydrochlorothiazide.

Electrolyte disturbances.

As with any diuretic, serum electrolyte levels should be monitored at regular intervals during hydrochlorothiazide therapy. Thiazide drugs, including hydrochlorothiazide, may cause disturbances in fluid and electrolyte balance (including hypokalemia, hyponatremia, and hypochloremic alkalosis). Signs of fluid and electrolyte imbalance include dry mouth, thirst, weakness, prolonged sleep, drowsiness, restlessness, muscle pain or cramps, muscle fatigue, arterial hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. The risk of hypokalemia is highest in patients with liver cirrhosis, a sudden increase in diuresis, inadequate oral electrolyte intake, or concomitant use of corticosteroids and ACTH. On the other hand, blockade of angiotensin II (AT1) receptors by olmesartan medoxomil, a component of Olspres N, may lead to hyperkalemia, particularly in patients with renal impairment and/or heart failure, as well as in patients with diabetes mellitus. Serum potassium levels should be appropriately monitored in these patients. Olspres N should be used with caution when administered concomitantly with potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes, or other drugs that may increase serum potassium levels. There are no data indicating that olmesartan medoxomil can prevent or mitigate diuretic-induced hyponatremia. Chloride deficiency is usually mild and does not require specific treatment. Thiazides may reduce urinary calcium excretion and cause a slight and transient increase in serum calcium concentration in the absence of any calcium metabolism disorders. Hypercalcemia may indicate occult hyperparathyroidism. Thiazides should be discontinued before parathyroid function testing. Thiazides enhance magnesium excretion in urine, potentially leading to hypomagnesemia. Hyponatremia of dilution may occur in edematous patients during hot weather.

Lithium preparations.

As with other drugs containing angiotensin II receptor blockers in combination with thiazides, Olspres N is not recommended for concomitant use with lithium preparations.

Sprue-like enteropathy

In very rare cases, severe chronic diarrhea with significant weight loss has been reported, developing several months or years after starting treatment with olmesartan; this is likely due to a localized delayed hypersensitivity reaction. Intestinal mucosal biopsies in such patients often show villous atrophy. If these symptoms occur in a patient during olmesartan therapy and other probable causes can be excluded, olmesartan therapy should be discontinued immediately and not restarted. If diarrhea does not resolve within one week after stopping the drug, the patient should consult a specialist (e.g., a gastroenterologist).

Acute myopia and secondary angle-closure glaucoma

Hydrochlorothiazide is a sulfonamide and may cause idiosyncratic reactions leading to choroidal effusion with visual field defects, acute transient myopia, and acute attacks of angle-closure glaucoma. Symptoms include acute onset of myopia or eye pain and typically occur within hours to weeks after starting treatment. Untreated acute angle-closure glaucoma may lead to permanent vision loss. Hydrochlorothiazide should be discontinued as soon as possible. If intraocular pressure cannot be controlled, immediate therapeutic or surgical intervention may be necessary. A history of allergy to sulfonamides or penicillin may be a risk factor for developing angle-closure glaucoma (see section "Adverse reactions").

Ethnic differences.

As with other angiotensin II receptor blockers, the antihypertensive effect of olmesartan medoxomil is somewhat less pronounced in Black patients compared to other ethnic groups (possibly due to lower renin levels in Black patients).

Anti-doping testing.

Hydrochlorothiazide, a component of this drug, may cause false-positive results in anti-doping tests.

Pregnancy.

Olspres N is contraindicated in pregnant women or women who are planning to become pregnant. If pregnancy is confirmed during treatment with Olspres N, therapy should be discontinued immediately and, if necessary, replaced with another drug approved for use during pregnancy.

Intestinal angioedema

Cases of intestinal angioedema have been reported in patients taking angiotensin II receptor blockers [including olmesartan] (see section "Adverse reactions"). These patients experienced abdominal pain, nausea, vomiting, and diarrhea. Symptoms resolved after discontinuation of angiotensin II receptor blockers. If intestinal angioedema is diagnosed, olmesartan therapy should be discontinued and appropriate monitoring initiated until symptoms completely resolve.

Other precautions.

Excessive reduction in blood pressure in patients with generalized atherosclerosis, ischemic heart disease, or ischemic cerebrovascular disease may lead to myocardial infarction or stroke.

The risk of allergic reactions to hydrochlorothiazide is higher in patients with a history of allergy or bronchial asthma, although such reactions may also occur in patients without such history.

According to scientific literature, thiazide diuretics may exacerbate or activate systemic lupus erythematosus.

Photosensitivity reactions may occur during treatment with thiazide diuretics. In such cases, discontinuation of the drug is recommended. If the physician considers it necessary to reinitiate treatment, patients should be advised to protect skin areas exposed to sunlight or artificial ultraviolet radiation.

Non-melanoma skin cancer.

An increased risk of non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) associated with higher cumulative doses of hydrochlorothiazide was observed in two epidemiological studies based on data from the Danish National Cancer Registry. The photosensitizing effect of hydrochlorothiazide may be a mechanism underlying the development of non-melanoma skin cancer.

Patients taking hydrochlorothiazide should be informed about the potential risk of non-melanoma skin cancer. Regular skin examinations for new lesions are recommended, and any suspicious skin changes should be reported immediately.

Patients should be informed about possible preventive measures, such as limiting exposure to sunlight and UV radiation and using adequate skin protection when such exposure occurs, to minimize the risk of skin cancer.

Any suspicious skin reactions should be promptly investigated, including histological examination of biopsy specimens.

In patients with a history of non-melanoma skin cancer, reconsideration of hydrochlorothiazide use may be appropriate (see section "Adverse reactions").

If a patient has intolerance to certain sugars, medical advice should be sought before taking this medication.

The drug contains lactose and should not be administered to patients with congenital galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Use during pregnancy or breastfeeding.

Pregnancy.

Olmesartan medoxomil.

Angiotensin II receptor blockers are contraindicated in pregnant women or women planning pregnancy.

Epidemiological data on teratogenic risk associated with the use of angiotensin II receptor blockers during the first trimester of pregnancy do not allow definitive conclusions, but a slight increase in risk cannot be excluded. Controlled epidemiological studies have not provided data on teratogenic risk with angiotensin II receptor blockers, but an increased risk of similar effects cannot be ruled out. Except in cases where angiotensin II receptor blockers are used for life-saving reasons, women planning pregnancy should be switched to other antihypertensive agents with proven safety during pregnancy. If pregnancy is diagnosed, angiotensin II receptor blockers should be discontinued immediately, and alternative therapy initiated if necessary.

It has been established that use of angiotensin II receptor blockers during the second and third trimesters of pregnancy may result in fetotoxic effects (impaired renal function, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, arterial hypotension, hyperkalemia).

If angiotensin II receptor blockers are used during the second trimester of pregnancy, ultrasound monitoring of fetal renal function and skull development is recommended.

Newborns whose mothers used angiotensin II receptor blockers should be closely monitored for the development of arterial hypotension.

Hydrochlorothiazide.

Experience with hydrochlorothiazide use during pregnancy, especially in the first trimester, is limited. Experimental animal data are insufficient. Hydrochlorothiazide crosses the placenta. Due to its mechanism of action, hydrochlorothiazide use during the second and third trimesters of pregnancy may impair fetoplacental circulation and adversely affect the fetus and newborn, causing jaundice, electrolyte disturbances, and thrombocytopenia.

Hydrochlorothiazide is not indicated for the treatment of edema in pregnancy, gestational hypertension, or preeclampsia, as it may reduce plasma volume and cause placental hypoperfusion without providing adequate therapeutic benefit.

Hydrochlorothiazide is also not recommended for the treatment of essential hypertension in pregnant women, except in exceptional cases where other drugs cannot be used.

The combination drug olmesartan medoxomil/hydrochlorothiazide is contraindicated in pregnant women or women planning pregnancy.

Breastfeeding period.

Olmesartan medoxomil.

There is currently no information on the use of Olspres N during breastfeeding; therefore, the drug should not be administered to breastfeeding women. Alternative drugs with proven safety during breastfeeding, especially when nursing newborns or preterm infants, may be used.

Hydrochlorothiazide.

Hydrochlorothiazide passes into breast milk in small amounts. High doses of thiazides causing intense diuresis may suppress breast milk production. If its use is absolutely necessary, breastfeeding should be discontinued.

The use of Olspres N during breastfeeding is not recommended. If Olspres N must be used during breastfeeding, the dose should be kept as low as possible.

Ability to affect reaction speed when driving or operating machinery.

Olspres N may have a minor or moderate effect on the ability to drive vehicles or operate machinery. Dizziness and increased fatigue may occasionally occur in patients receiving antihypertensive therapy, which may impair reaction time.

Method of Administration and Dosage

Adults.

Olspres N is not a first-line agent. It is intended for patients in whom treatment with olmesartan medoxomil alone at a dose of 20 mg does not achieve the required level of blood pressure control.

Olspres N tablets should be taken once daily, independently of food intake.

In the presence of clinical indications, transition from monotherapy with olmesartan medoxomil 20 mg directly to the combination drug is permitted; however, it should be noted that the maximum antihypertensive effect of olmesartan medoxomil is achieved after 8 weeks of treatment initiation.

Dose titration of each component is recommended.

Olmesartan medoxomil/hydrochlorothiazide 20/12.5 mg may be prescribed to patients in whom treatment with olmesartan medoxomil alone at a dose of 20 mg does not achieve the required blood pressure control.

Olmesartan medoxomil/hydrochlorothiazide 20/25 mg may be prescribed to patients in whom treatment with olmesartan medoxomil/hydrochlorothiazide 20/12.5 mg does not achieve the required blood pressure control.

Elderly Patients (aged 65 years and older).

The combination drug is recommended for elderly patients at the same dosage as for adult patients.

Renal Impairment.

When Olspres N is administered to patients with mild to moderate renal impairment (creatinine clearance 30–60 mL/min), periodic monitoring of renal function is recommended. Olspres N is contraindicated in patients with severe renal impairment (creatinine clearance < 30 mL/min) (see sections "Contraindications", "Special Warnings and Precautions for Use", "Pharmacological Properties").

Hepatic Impairment.

Olspres N should be used with caution in patients with mild to moderate hepatic impairment. In patients with moderate hepatic impairment, olmesartan medoxomil should be initiated at a dose of 10 mg once daily, and the maximum dose should not exceed 20 mg once daily. Patients with hepatic impairment who are already receiving diuretics and/or other antihypertensive agents should be closely monitored for blood pressure and renal function. Experience with olmesartan medoxomil in patients with severe hepatic impairment is lacking. Olspres N is contraindicated in patients with severe hepatic impairment, as well as in those with cholestasis or biliary obstruction (see sections "Contraindications", "Pharmacological Properties").

Method of Administration.

Tablets should be swallowed whole with sufficient fluid (e.g., a glass of water). Tablets should not be chewed. The drug should be taken daily at the same time.

Children.

The safety and efficacy of Olspres N in children (under 18 years of age) have not been established. Data are lacking.

Overdose.

Specific information regarding symptoms or treatment of Olspres N overdose is lacking.

Close monitoring of the patient and symptomatic supportive treatment are required. Treatment is symptomatic and depends on the time elapsed since drug ingestion and the severity of symptoms. Emetics and/or gastric lavage may be recommended. Activated charcoal may sometimes be recommended in the management of overdose. Serum electrolyte and creatinine levels should be monitored regularly. In case of arterial hypotension, the patient should be placed in a supine position and promptly administered intravenous infusion of isotonic sodium chloride solution.

The most likely manifestations of olmesartan medoxomil overdose are arterial hypotension and tachycardia; bradycardia may also occur. Hydrochlorothiazide overdose is associated with electrolyte disturbances (hypokalemia, hypochloremia) and dehydration due to excessive diuresis. The most common symptoms of overdose are nausea and drowsiness. Hypokalemia may cause muscle cramps and/or exacerbate arrhythmias induced by concomitant medications (cardiac glycosides or certain antiarrhythmics).

It is unknown whether olmesartan or hydrochlorothiazide is removed by hemodialysis.

Adverse reactions.

The most common adverse reactions associated with the use of the drug are headache, dizziness, and increased fatigue.

Hydrochlorothiazide may cause or exacerbate hypovolemia, which may lead to disturbances in electrolyte balance.

The following terminology was used to classify the frequency of adverse reactions: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), not known (cannot be estimated from the available data).

*During the post-marketing period, cases of autoimmune hepatitis with a latency period of several months to years have been reported, which were reversible after discontinuation of olmesartan.

There have been reports of isolated cases of rhabdomyolysis temporally associated with the use of angiotensin II receptor blockers.

The following adverse reactions have been reported with hydrochlorothiazide: dry mouth, thirst, anaphylactic shock, coma, Stevens–Johnson syndrome, disorientation, mood changes, pneumonitis. The use of thiazide diuretics may lead to decreased glucose tolerance, which in turn may result in the manifestation of latent diabetes mellitus. Hypochloremic alkalosis may occur during hydrochlorothiazide therapy, which may trigger gout attacks in patients with asymptomatic gout.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after drug authorization is of great importance. It allows continuous monitoring of the benefit-risk ratio of the drug. Healthcare professionals, pharmacists, as well as patients or their legal representatives should report all suspected adverse reactions and lack of drug efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C.

Keep out of reach of children.

Packaging.

10 tablets per blister; 3 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "KYIV VITAMIN PLANT".

Manufacturer's address and location of business activity.

38 Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua