Index of drugs

Treatment of essential hypertension in adults whose blood pressure is not sufficiently controlled with candesartan cilexetil or hydrochlorothiazide monotherapy.

1 tabl contains candesartan cilexetil and hydrochlorothiazide, respectively: 8 mg + 12.5 mg or 16 mg + 12.5 mg or 32 mg + 12.5 mg or 32 mg + 25 mg. The preparation contains lactose.

Antihypertensive preparation containing two antihypertensive agents with complementary mechanisms of action: angiotensin II receptor antagonist (candesartan) and thiazide diuretic (hydrochlorothiazide). Candesartan cilexetil is a pro-drug which, when absorbed from the gastrointestinal tract, is rapidly converted (by ester hydrolysis) to the active form - candesartan. Candesartan is a potent and specific angiotensin II receptor antagonist. It acts selectively on the AT receptor subtype₁by blocking the effects of angiotensin II. It has no agonist activity towards the AT receptor₁, is also not an ACE inhibitor - an enzyme that converts angiotensin I to angiotensin II and breaks down bradykinin. Therefore, unlike ACE inhibitors, the likelihood of coughing is low. It does not bind or block other hormone receptors or ion channels that play a role in the regulation of the circulatory system. Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the reabsorption of electrolytes in the renal tubules, directly increasing the excretion of sodium and chloride and water. The excretion of potassium and Magnesium by the kidneys increases in a dose-dependent manner, whereas Calcium is more reabsorbed. Hydrochlorothiazide reduces plasma volume and extracellular fluid, decreases cardiac output and decreases blood pressure. During long-term treatment, a reduction in peripheral resistance contributes to lowering the blood pressure. Co-administration of candesartan and hydrochlorothiazide does not affect the pharmacokinetics of any of these active substances. Bioavailability of candesartan given in the form of is approximately 34%, C_max occurs after 3-4 hours. Candesartan is strongly bound to plasma proteins (> 99%). A small part of the drug is metabolised in the liver with the participation of CYP2C9. It is excreted mainly in unchanged form with urine and bile. T_0,5 is about 9 hours. Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract, with a total bioavailability of about 70%. It binds to plasma proteins in about 60%. It is not metabolized, it is almost completely excreted unchanged in the urine. T_0,5 is about 8 hours.

Hypersensitivity to candesartan, hydrochlorothiazide, other sulphonamide derivatives or to any of the excipients. Severe renal dysfunction (creatinine clearance <30 ml / min / 1.73 m² pc.). Severe liver dysfunction and / or cholestasis. Guided hypokalemia and hypercalcemia. Gout. Co-administration with aliskiren in patients with diabetes or renal impairment (GFR <60 ml / min / 1.73 m²). II and III trimester of pregnancy.

Patients with primary hyperaldosteronism generally do not respond to treatment with antihypertensive drugs acting through the inhibition of the renin-angiotensin system (RAA) - the use of the preparation in these cases is not recommended. In patients with impaired liver function or progressive liver disease, thiazides should be used with caution, as slight changes in fluid and electrolyte balance may lead to hepatic coma. There is no clinical experience with the use of a combined preparation in patients with impaired liver function. In patients with renal impairment, loop diuretics are more favorable than the thiazides. If the drug is used in patients with impaired renal function, periodic monitoring of potassium, creatinine and uric acid levels is recommended. There are no data on the use of the preparation in patients after recent kidney transplantation.In patients with bilateral renal artery stenosis or stenosis of the artery to a single kidney, candesartan may increase the concentration of urea and creatinine in the blood. In patients whose vascular tone and renal function depend mainly on RAA activity (eg patients with severe congestive heart failure or kidney disease, including renal artery stenosis), candesartan may result in sudden lowering of blood pressure, azotemia, oliguria and rare - acute renal failure. Due to the risk of hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure), dual RAA blocking is not recommended (eg, by the combined use of an angiotensin II receptor antagonist with an ACE inhibitor or aliskiren); if the use of the RAA double block is absolutely necessary, it should only be carried out under the supervision of a specialist, renal function, electrolyte concentration and blood pressure should be monitored. At the same time, angiotensin II receptor antagonists and ACE inhibitors should not be used in patients with diabetic nephropathy. In patients with hypovolaemia and / or sodium deficiency, symptomatic hypotension may occur after administration of the preparation - these disorders should be corrected before administration. In patients treated with angiotensin II receptor antagonists, hypotension due to RAA system suppression may occur during anesthesia and / or surgery; very rarely hypotension can be so severe that it may be necessary to administer intravenous fluids and / or prescription drugs. As with other antihypertensive agents, excessive hypotension in patients with ischemic heart disease or with cerebrovascular atherosclerotic lesions can cause heart attacks or strokes. Special care should be taken in patients with haemodynamically significant aortic or mitral valve stenosis or with hypertrophic cardiomyopathy with narrowing of the outflow route. During treatment with the preparation, the concentration of electrolytes in the blood should be checked regularly; there is a risk of hypokalemia, hyponatremia, hypochilosis alkalosis, hypomagnesaemia and slight hypercalcaemia, associated with the use of hydrochlorothiazide (a significant hypercalcemia may be a symptom of latent hyperparathyroidism); on the other hand, there is a risk of hyperkalemia associated with the use of candesartan. Although hypokalaemia may occur with thiazide diuretics, combination therapy with candesartan may reduce the diuretic-induced hypokalemia. The risk of hypokalemia is greatest in patients with liver cirrhosis, in patients with increased diuresis, in patients receiving orally inadequate amounts of electrolytes and in patients treated concomitantly with corticosteroids or ACTH. However, the risk of hyperkalemia is higher when there is a renal dysfunction and / or heart failure. Use with potassium-sparing diuretics, potassium supplements, potassium salt substitutes and other medicines that may cause hyperkalaemia with caution. Appropriate monitoring of serum potassium in patients at risk is recommended. Caution use in diabetic patients, because treatment with thiazide may impair Glucose tolerance - you may need to adjust the dose of insulin or oral antidiabetic medicines. Thiazides may accelerate the onset of diabetes in patients with latent diabetes; may cause systemic lupus erythematosus to become active or exacerbated; they can cause hyperuricemia and cause an attack of susceptible patients. The use of thiazide diuretics may be associated with an increase in cholesterol and triglycerides. The occurrence of a hypersensitivity reaction to hydrochlorothiazide is more likely in patients with allergy and asthma. In case of hypersensitivity reactions to light, it is recommended to discontinue the drug; if it is necessary to restart the diuretic therapy, it is recommended to protect the body against sunlight or artificial UV radiation. Due to the lactose content, the preparation should not be used in patients with hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

The use of the preparation in the first trimester of pregnancy is not recommended (there is a risk of teratogenic effect).Use in the second and third trimester of pregnancy is contraindicated. Candidartrate used in the second and third trimester of pregnancy is toxic to fetal development (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and newborn (renal failure, hypotension, hyperkalemia) - in cases where exposure to candesartan occurred since the second trimester of pregnancy, it is recommended an ultrasound examination of the fetus skull and kidneys; children whose mothers took the drug during pregnancy should be closely monitored for hypotension. Hydrochlorothiazide crosses the placental barrier and may cause effects in the fetus and newborn, such as electrolyte disturbances, jaundice, and thrombocytopenia. It is not recommended to use the product during breastfeeding.

Undesirable effects on individual components may be potential adverse events when using a combined preparation.candesartan. Common: respiratory tract infections, dizziness, headache. Very rare: leukopenia, neutropenia, agranulocytosis, hyperkalemia, hyponatremia, cough, nausea, increased liver enzymes, liver dysfunction or inflammation of the liver, angioneurotic edema, rash, urticaria, pruritus, back pain, joint pain, muscle pain, kidney dysfunction (including renal failure in hypersensitive patients).hydrochlorothiazide. Thiazides, including hydrochlorothiazide, can cause fluid and electrolyte imbalance (hypercalcaemia, hypokalaemia, hyponatremia, hypomagnesaemia and hypochloraemia alkalosis). Common: hyperglycemia, hyperuricaemia, electrolyte imbalance, feeling of "emptiness in the head", dizziness, glycosuria, weakness, increased cholesterol and triglycerides in the blood Uncommon: orthostatic hypotension, anorexia, anorexia, gastric irritation, diarrhea, constipation , rash, urticaria, photosensitivity reactions Rare: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, aplastic anemia, bone marrow suppression, haemolytic anemia, anaphylactic reactions, sleep disturbances, depression, anxiety, paresthesia, transient blurred vision, arrhythmias , necrotizing polyarteritis (vasculitis, cutaneous vasculitis), acute respiratory failure (including alveolitis and pulmonary edema), pancreatitis, jaundice (with intrahepatic cholestasis), toxic necrotic decay of the epidermis, reactions reminiscent cutaneous cutaneous lupus, activation of cutaneous lupus erythematosus, muscle cramps, renal dysfunction and interstitial nephritis, fever, increase in bovine nitrogen (BUN) and creatinine in the blood. Not known: acute myopia, acute glaucoma with closed angle.

Orally. Adults: 1 tabl. once a day. It is recommended to individually adjust the dose of individual components of the preparation. In clinically relevant cases, a direct change from monotherapy to a combined preparation may be considered. If the hydrochlorothiazide monotherapy changes to the use of a combined preparation, a dose adjustment of candesartan is recommended. Full antihypertensive effect is usually achieved within 4 weeks of starting treatment.Special groups of patients. There is no need to change the dose in elderly patients. In patients at risk of hypotension (eg in patients with decreased intravascular volume), a titre of candesartan should be titrated (an initial dose of 4 mg candesartan should be considered in this patient group). In patients with mild to moderate renal impairment (CCr ≥ 30 ml / min) or mild to moderate hepatic impairment, gradual titration of candesartan is recommended prior to initiation of the combination (the recommended initial dose of candesartan is 4 mg in these patients). Do not use in patients with severe renal impairment (CCr <30 ml / min) or severe liver problems and / or cholestasis. The safety and efficacy of the preparation in children and adolescents <18 years have not been established.Way of giving. It can be taken with or without food. The dividing line on the tablet only facilitates crushing to facilitate swallowing, not splitting into equal doses.