Index of drugs

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

1 tabl contains 8 mg or 16 mg candesartan cilexetil and 12.5 mg hydrochlorothiazide. The tablets contain 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 receptor₁It does not bind and does not block other hormone receptors and ion channels that play a role in the regulation of the circulatory system. Hydrochlorothiazide inhibits the active reabsorption of sodium, mainly in the channels of distal kidneys, and increases the excretion of sodium, chloride and water. The elimination of potassium and Magnesium by the kidneys increases in a dose-dependent manner, while increasing Calcium reabsorption. Hydrochlorothiazide reduces plasma volume and extracellular fluid, decreases cardiac output and decreases blood pressure. Bioavailability of candesartan given in the form of is about 34%. C_maxCandesartan in the blood occurs after 3-4 hours. Candesartan is highly bound to plasma proteins (over 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 an absolute 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 sulfonamide derivatives or other components of the preparation. Severe renal dysfunction (creatinine clearance <30 ml / min / 1.73 m² pc.). Severe liver dysfunction and / or cholestasis. Guided hypokalemia and hypercalcemia. Gout. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²). II and III trimester of pregnancy.

Patients with primary hyperaldosteronism usually do not respond to treatment with antihypertensive drugs acting through the inhibition of the renin-angiotensin-aldosterone system - 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 a 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 the activity of the renin-angiotensin-aldosterone system - RAA (eg patients with severe congestive heart failure or kidney disease, including renal artery stenosis), candesartan may cause a sudden fall in blood pressure , azotemia, oliguria and rarely - acute renal failure.The concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalaemia and renal dysfunction (including acute renal failure) - therefore, dual blocking of the RAA system is not recommended by concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren. If the use of a dual RAA blockade is absolutely necessary, it should only be carried out under the supervision of a specialist, and the vital parameters of the patient, such as kidney function, electrolyte concentration and blood pressure should be closely monitored. In patients with diabetic nephropathy, ACE inhibitors and angiotensin II receptor antagonists should not be used concurrently. In patients with hypovolaemia and / or sodium deficiency, symptomatic hypotension may occur after administration of the preparation - the use of the preparation is not recommended until the patient is in good condition. 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 narrowing cardiomyopathy. During treatment with the product, the concentration of electrolytes in the blood should be checked regularly. Although hypokalaemia may occur with thiazide diuretics, combination therapy with candesartan may reduce the diuretic-induced hypokalemia. The risk of hypokalemia is higher 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. Candidartan may, however, cause hyperkalaemia, especially if 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. Hydrochlorothiazide may cause slight and transient hypercalcaemia; significant hypercalcemia may be evidence of concomitant hyperparathyroidism. The use of thiazide diuretics should be discontinued before performing tests to evaluate parathyroid function. 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. In addition, thiazides may cause or worsen systemic lupus erythematosus. The occurrence of a hypersensitivity reaction to hydrochlorothiazide is more likely in patients with a history of allergy or bronchiectasis. Thiazide diuretics can cause hypersensitivity to light (if it occurs, treatment should be discontinued); if it is necessary to resume therapy with a diuretic, it is recommended to protect the body against sunlight or artificial UVA radiation. The safety and efficacy of the preparation in children and adolescents <18 years have not been established. 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; infants whose mothers took the drug during pregnancy should be closely monitored for hypotension. Hydrochlorothiazide crosses the placental barrier. Used in the second and third trimester of pregnancy may reduce the blood flow through the placenta and may cause such effects in the fetus and newborn, such as electrolyte abnormalities, jaundice and thrombocytopenia.The drug should not be used to treat oedemas in pregnant women, gestational hypertension and preeclampsia. Hydrochlorothiazide should not be used in the treatment of essential hypertension in pregnant women except in rare cases where no other treatment can be used. The preparation is not recommended during breastfeeding; in case of administration, the lowest possible dose should be used. There are no data on the use of candesartan during lactation; It is recommended to administer drugs with an established safety profile, especially when feeding newborns and premature babies. Thiazides are excreted in breast milk; they can inhibit lactation.

Undesirable effects on individual components may be potential adverse events when using a combined preparation.candesartan. Common: respiratory tract infections, pain and dizziness. 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 may cause water-electrolyte imbalance (hypercalcemia, hypokalaemia, hyponatremia, hypomagnesaemia and hypochloraemia alkalosis) and increase serum uric acid (in sensitive patients, they may cause gout). 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, loss of appetite, 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, paresthesias, transient blurred vision, arrhythmias , necrotizing polyarteritis (vasculitis, vasculitis), respiratory failure (including inflammation and pulmonary edema), pancreatitis, jaundice (with intrahepatic cholestasis), toxic epidermal necrolysis, reactions of type Lupus erythematosus, activation of rnego lupus erythematosus, muscle spasms, renal dysfunction and interstitial nephritis, fever, increased plasma urea nitrogen 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), dose adjustment of candesartan is recommended (an initial dose of 4 mg candesartan should be considered in this patient group). In patients with mild to moderate renal impairment (creatinine clearance ≥30 ml / min / 1.73 m² p.) or mild to moderate hepatic impairment, dose adjustment of candesartan is recommended prior to initiation of the combination (the recommended initial dose of candesartan is 4 mg in these patients). The drug can be taken regardless of meals.