Index of drugs

Arterial hypertension if treatment with a combined preparation is indicated. The preparation is not suitable for initiating or determining a dose, but it substitutes the administration of 10 mg benazepril hydrochloride and 12.5 mg hydrochlorothiazide or 20 mg benazepril hydrochloride and 25 mg hydrochlorothiazide in separate maintenance treatments.

1 tabl powl. contains 10 mg benazepril hydrochloride and 12.5 mg hydrochlorothiazide or 20 mg benazepril hydrochloride and 25 mg hydrochlorothiazide. The preparations contain lactose.

Benazepril hydrochloride is hydrolyzed in the liver to benazeprilat, which is an inhibitor of an angiotensin converting enzyme (ACE). ACE inhibition leads to a reduction in the production of substances with vasoconstriction - angiotensin II - in tissues and blood plasma, which results in a reduction of aldosterone secretion and, consequently, an increase in serum potassium. The abolition of the negative feedback between angiotensin II and renin secretion leads to increased plasma renin activity. In hypertensive patients, it lowers blood pressure in both supine and standing position without compensatory acceleration of cardiac function. It significantly reduces peripheral arterial resistance. In the majority of patients, antihypertensive effect appeared after about 1 hour after oral administration, and the strongest was after 2-4 h; the maximum antihypertensive effect was usually achieved after 3-4 weeks. Abrupt discontinuation of treatment does not cause a rapid and significant increase in blood pressure. After oral administration, about 37% of the dose is absorbed, then the precursor is quickly converted into a pharmacologically active metabolite - benazeprilat, which reaches a maximum concentration after 1.5 hours. About 95% of benazepril and benazeprilat are bound to plasma proteins. Benazepril is eliminated mainly as a result of biotransformation, benazeprilat is excreted in the urine and bile. In patients with severe renal impairment, the kinase of benazeprilat is significantly impaired. Hydrochlorothiazide is a benzothiadiazine. It works directly on the kidneys by increasing the excretion of sodium chloride, and thus the water associated with it. Their main site of clinical significance is the initial section of the distal tubule; they also inhibit the independent of the electrical potential of sodium chloride back-up through the cell's luminal membrane. The elimination of potassium and Magnesium is increased and Calcium is reduced. Hydrochlorothiazide causes slight excretion of bicarbonates, and excretion of chlorides is higher than sodium. Elimination of electrolytes and water begins after 2 hours, is the highest after 3-6 h and persists for 6-12 h. Antihypertensive effect appears after 3-4 days and lasts up to a week after the end of treatment. Hydrochlorothiazide is absorbed 60-75% after oral administration. With proteins, it is 65% bound. Over 95% of the absorbed dose is excreted unchanged in the urine. T_0,5 in the elimination phase, it is 6-8 hours.

Hypersensitivity to benazepril hydrochloride, thiazides, sulfonamides (possible cross reactions) or to any of the excipients. Angioneurotic edema or swelling of a different type (eg associated with previous treatment with an ACE inhibitor). Severe renal impairment (serum creatinine <1.8 mg / dl or creatinine clearance <30 ml / min). Dialysis. Narrowing of the renal arteries (bilateral or one active kidney). Condition after kidney transplantation. Haemodynamically significant aortic or mitral valve stenosis or hypertrophic cardiomyopathy. Uncompensated heart failure. Primary hyperaldosteronism. Primary liver dysfunction or liver failure. Clinically significant electrolyte disturbances (hypercalcemia, hyponatremia, hypokalaemia). Children. Pregnancy and breastfeeding. During the treatment, dialysis or haemofiltration should not be performed using polyacrylonitrile or high permeability dialysis polysodium-2-methylalylsulphonate membranes (eg, AN 69). In case of urgent dialysis or haemofiltration, other treatment of hypertension or heart failure should be used - do not use ACE inhibitors or use another type of dialysis membrane. During LDL (low density lipoprotein) scintigraphy with dextarnin sulfate, there may be a life-threatening anaphylactoid reaction associated with ACE inhibitors. During desensitisation treatment of insect venom (eg bee and wasp stings) and concomitant use of ACE inhibitors, anaphylactoid reactions may occur (e.g.lowering of blood pressure, shortness of breath, vomiting, skin allergic reactions), which in some cases may be life-threatening. If you need LDL scandal or desensitization, the ACE inhibitor should be temporarily replaced with another preparation used to treat hypertension and heart failure. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²).

The preparation can be used only after a very critical risk-benefit assessment, regularly monitoring the clinical condition and laboratory parameters in the case of: clinically significant proteinuria (> 1 g / day); impaired immune response or collagenosis (e.g., lupus erythematosus, scleroderma); simultaneous, systemic administration of preparations that inhibit the immune response (e.g., corticosteroids, cytostatics, anti-metabolites), Allopurinol, procainamide or lithium; gout; reduction of intravascular volume, atherosclerosis of cerebral vessels; coronary atherosclerosis; diabetes or diabetes mellitus; hepatic impairment. Check the kidneys before using the product. Particularly at the beginning of treatment, the preparation should be used strictly to control the pressure and / or laboratory parameters in patients with salt and / or fluid deficiency, with impaired renal function (serum creatinine up to 1.8 mg / dl or creatinine clearance 30-60 ml / min), with severe hypertension, aged> 65 years. As with other ACE inhibitors and angiotensin II antagonists, the drug is less effective in lowering blood pressure in black patients than in non-black patients. In the case of jaundice or a significant increase in liver enzymes and in severe skin reactions, the preparation should be discontinued. 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. Due to the lactose content, the preparation should not be used in patients with galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

The drug is contraindicated during pregnancy and breastfeeding. If planning or confirming a pregnancy, other treatments should be taken as soon as possible. If mother's treatment is necessary, breast-feeding should be discontinued.

Common: especially at the beginning of treatment, as well as in patients with salt and / or liquid deficiency (eg due to vomiting, diarrhea, prior use of diuretics), severe hypertension, and when increasing the dose of the preparation, excessive hypotension may occur blood (hypotension, orthostatic hypotension), with symptoms such as dizziness, feelings of weakness, blurred vision, and in uncommon cases also with loss of consciousness (fainting); ECG changes and arrhythmias (in patients using hydrochlorothiazide due to hypokalemia); occurrence or worsening of renal dysfunction; dry cough, bronchitis; nausea, abdominal discomfort, digestive disorders; cutaneous allergic reactions such as rash, pruritus, redness; headache, fatigue, drowsiness, weakness, apathy; reduction in hemoglobin, hematocrit, leucocytes or platelets; especially in patients with impaired renal function there may be an increase in urea, creatinine and potassium in the blood serum and a decrease in serum sodium. Uncommon: proteinuria, sometimes accompanied by deterioration of renal function; dyspnoea, sinusitis, rhinitis; vomiting, diarrhea, constipation, loss of appetite, pancreatitis,especially in the case of previous cholelithiasis, acute cholecystitis; syndrome beginning with cholestatic jaundice and progressing to liver necrosis (sometimes fatal); urticaria, pemphigus, Stevens-Johnson syndrome, cutaneous lupus erythematosus, toxic epidermal necrolysis; angioneurotic edema including lips, face and / or limbs (more commonly in black patients); thrombosis and embolism (when using high doses of hydrochlorothiazide) as a result of blood compaction, especially in elderly patients or in the case of venous disorders; reducing the production of tears; depression, feelings of "emptiness" in the head, insomnia, nervousness, impotence, paresthesia, balance disorders, confusion, mood disorders, anxiety, tinnitus, blurred vision and taste disorders or transient loss of taste; muscle spasms, skeletal muscle weakness, muscle pain and paresis due to hypokalemia; anemia (including aplastic anemia), thrombocytopenia, leukopenia, neutropenia, eosinophilia, and in individual cases agranulocytosis or pancytopenia, especially in patients with renal impairment, collagenosis or concomitantly with allopurinol; procainamide or specific medicines that inhibit the immune response. Isolated cases: tachycardia, palpitations, arrhythmia, angina pectoris, myocardial infarction, transient ischemic attack (TIA), cerebrovascular accident; non-bacterial interstitial nephritis followed by acute renal failure; sudden pulmonary edema with symptoms of shock; angioedema involving the larynx, throat and / or tongue; liver dysfunction, hepatitis and obstruction (partial bowel); erythema multiforme, which may be accompanied by fever, muscle pain, joint pain / inflammation, vasculitis, eosinophilia, leukocytosis and / or increased antinuclear antibodies and accelerated OB; anaphylactoid reactions, psoriasis-like skin lesions, hypersensitivity to light; abundant sweating, baldness, separation of nails from the placenta and intensification of Raynaud's symptom; haemolysis / hemolytic anemia, also associated with glucose-6-phosphate dehydrogenase deficiency; hypokalemia, hypochloremia, hypomagnesemia, hypercalcemia, glucosuria, metabolic alkalosis, increased Glucose, cholesterol, triglycerides, uric acid and serum amylase, increased bilirubin and liver enzymes. In patients with diabetes, an increase in serum potassium was observed. Increased protein excretion in the urine may occur.

Treatment of hypertension should start with a small, gradually increased dose of a single active substance. Do not increase the dose of the combined preparation if there is no response to treatment. The dose should be individually adjusted to the patient's needs. The usual dose is 1 tablet. powl. containing 10 mg benazepril and 12.5 mg hydrochlorothiazide daily. If the blood pressure is not adequately reduced by the use of the preparation, 2 tablets containing 10 mg benazepril and 12.5 mg hydrochlorothiazide or 1 tablet containing 20 mg benazepril hydrochloride and 25 mg hydrochlorothiazide per day may be administered after gradual increase in the dosage of active substances in separate formulations. In isolated cases, the use of 20 mg benazepril and 25 mg hydrochlorothiazide twice daily, morning and evening may be considered. The dose should be increased at intervals of not less than 3-4 weeks. In patients with moderate renal impairment and in elderly patients, caution should be exercised when increasing the dose of individual components.
The preparation can be taken with or without food. The recommended daily dose should be taken in the morning with a lot of liquid. Do not divide the coated tablets.