Index of drugs

Treatment of hypertension in adult patients whose blood pressure is not sufficiently controlled with cilazapril monotherapy.

1 tabl powl. contains 5 mg of cilazapril and 12.5 mg of hydrochlorothiazide. The drug contains lactose.

Antihypertensive preparation - combination of an ACE inhibitor (cilazapril) with a diuretic (hydrochlorothiazide). The hypotensive effect of the combination of both components is additive. Cilazapril is converted into the active metabolite - cilazaprilat - a long-acting ACE inhibitor that inhibits the activity of the renin-angiotensin-aldosterone system by inhibiting the conversion of angiotensin I to angiotensin II, a substance that tightly constricts blood vessels. The effect of cilazapril in hypertensive patients persists for 24 h. Hydrochlorothiazide increases the excretion of sodium and chloride and to a lesser extent the excretion of potassium and Magnesium, increasing diuresis and acting hypotensive. It increases plasma renin activity and aldosterone secretion, which results in a decrease in potassium in the blood. Cilazapril is effectively absorbed and quickly converted by ester hydrolysis to the active form - cilazaprilat. The bioavailability of cilazaprilat after oral administration is approximately 60%. C_max Cilazaprilat in the blood is achieved within 2 hours. Cilazaprilate is excreted unchanged in the urine. T_0,5 is about 9 hours. C_max hydrochlorothiazide in the blood occurs within 2 h and its bioavailability is about 65%. It is excreted mainly in unchanged form in the urine. T_0,5 is 7-11 hours.

Hypersensitivity to cilazapril, other ACE inhibitors, hydrochlorothiazide, other thiazide diuretics, sulfonamides or any of the excipients. History of angioedema after treatment with ACE inhibitors. Hereditary or idiopathic angioneurotic edema. Impaired renal function (creatinine clearance <30 ml / min / 1.73 m²) or without. Co-administration with aliskiren in patients with diabetes or renal impairment (GFR <60 ml / min / 1.73 m²). II and III trimester of pregnancy.

Treatment can only be started in patients who have had their blood pressure checked during the administration of the individual active substances in the same doses as in the combined preparation. Particularly cautiously use in patients with stimulation of the renin-angiotensin-aldosterone system - RAA (renal arterial hypertension, other causes of renal hypoperfusion, severe heart failure, hyponatraemia, hypovolemia, previous treatment with vasodilators or diuretics), due to the risk of significant hypotension and impaired renal function (medical supervision is necessary, and treatment should be started with a small dose, very carefully increased, if possible, discontinuation of diuretic therapy should be temporarily stopped). If hypotension occurs, the patient should be placed on the back and filled up with fluid volume; drug administration can be continued after supplementing the intravascular volume, but if hypotension persists, the dose should be reduced or discontinued. Similar caution should be exercised in patients with angina or cerebrovascular disease in whom hypotension can cause ischaemia of the myocardium or brain. In patients with renal artery stenosis, cilazapril, like other substances acting on the RAA system, increases the risk of renal failure (including acute renal failure) - caution should be used in these patients; if renal failure occurs, treatment should be discontinued. In patients with moderate renal impairment, the dosage of cilazapril should be adjusted for creatinine clearance. In patients with impaired renal function, monitoring of potassium and creatinine levels is part of standard medical treatment. Due to the risk of hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure), it is not recommended to use a dual RAA blockade (e.g.through the combined use of an ACE inhibitor with an angiotensin II receptor antagonist 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. At the same time, ACE inhibitors and angiotensin II receptor antagonists should not be used in patients with diabetic nephropathy. ACE inhibitors are less effective in lowering blood pressure in black patients. The risk of angioedema is higher in black patients. Patients with a history of angioneurotic edema, unrelated to the use of ACE inhibitors may be at higher risk of angioedema. Anaphylactic reactions may occur in patients receiving ACE inhibitors and dialyzed using high-flow dialysis membranes, eg AN69 (use a different type of membrane or antihypertensive agent from another group) during LDL apheresis with dextran sulphate (discontinue treatment with ACE inhibitor before each apheresis) or in patients undergoing desensitisation, e.g. Hymenoptera venom (you should temporarily discontinue an ACE inhibitor and not replace it with a β-blocker). In patients receiving ACE inhibitors who have developed jaundice or who have a significant increase in liver enzymes, treatment should be discontinued. Cilazapril is not recommended for patients with ascites; especially cautiously use in patients with liver cirrhosis, without ascites (risk of significant hypotension, treatment should be started with a low dose). The use of thiazides in patients with liver cirrhosis may precipitate hepatic encephalopathy, resulting from small changes in water and electrolyte balance. Due to the risk of neutropenia and agranulocytosis, it is recommended to periodically determine the number of leukocytes in patients with renal insufficiency, vascular collagenosis or receiving immunosuppressive therapy. Patients with diabetes should be closely monitored for glycemia. Exercise caution in patients with narrowing of the left ventricle outflow pathway (eg, mitral valve stenosis, aortic stenosis, hypertrophic cardiomyopathy); when using hypotensive agents (if hypotension occurs due to this mechanism, they can be corrected by increasing the intravascular volume); with a history of gout (risk of gout attack, due to the hyperuricemic effect of hydrochlorothiazide); with porphyria (risk of exacerbation of the disease); in the elderly (decreased clearance of both cilazapril and hydrochlorothiazide). Renal function and blood electrolytes should be monitored in all patients taking the medicine. Due to cilazapril, hyperkalaemia may occur in patients with impaired renal function and / or taking potassium supplements (including salt substitutes). Due to hydrochlorothiazide, hypokalaemia may occur during treatment, although the risk is lower than in patients receiving thiazide as monotherapy. Thiazides may also cause hyponatremia and dehydration; the risk of hyponatremia is greater in women, patients with hypokalemia or low in sodium / salt and in the elderly. It is not recommended for use in children and adolescents <18 years (no data on safety and efficacy in this age group). Due to the lactose content, the drug should not be used in patients with galactose intolerance, Lapp lactase deficiency, malabsorption of glucose-galactose.

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. Cilazapril 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) - when exposure to the drug occurred from the second trimester of pregnancy, it is recommended an ultrasound examination of the fetus skull and kidneys; newborns whose mothers took the drug during pregnancy should be closely monitored for hypotension. Hydrochlorothiazide crosses the placenta. Used in the second and third trimester of pregnancy may worsen placental-fetal perfusion and may cause fetus and newborn jaundice, electrolyte disturbances and thrombocytopenia.The drug is not recommended during breastfeeding, especially breastfeeding newborns or premature babies.

cilazapril. Common: pain and dizziness, cough, nausea, tiredness. Uncommon: agranulocytosis, thrombocytopenia, anemia, angioneurotic edema, anaphylaxis, lupus-like syndrome, taste disorders, cerebral ischemia, transient ischemic attack, ischemic stroke, peripheral neuropathy, myocardial ischemia, angina pectoris, tachycardia, palpitations, myocardial infarction, arrhythmia , hypotension, orthostatic hypotension, shortness of breath, bronchospasm, rhinitis, interstitial lung disease, bronchitis, sinusitis, dry mouth, aphthous stomatitis, decreased appetite, diarrhea, vomiting, inflammation of the tongue, pancreatitis, abnormal results liver tests (including ALT, AST, GGT, bilirubin, alkaline phosphatase), cholestatic hepatitis with or without necrosis, rash, maculopapular rash, psoriatic dermatitis, psoriasis (exacerbation), lichen planus, exfoliative dermatitis, urticaria a, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigoid pemphigoid, pemphigus, Kaposi's sarcoma, vasculitis / purpura, photosensitivity, alopecia, separation of the nail from the placenta, muscle cramps, muscle pain, arthralgia, impaired renal function, acute renal failure, increased creatinine or urea in the blood, hyperkalemia, hyponatraemia, proteinuria, nephrotic syndrome, nephritis, impotence, gynecomastia, hyperhidrosis, flushing (especially the face), weakness, sleep disorders.hydrochlorothiazide. Common: dizziness, nausea, tiredness. Uncommon: thrombocytopenia, haemolytic anemia, bone marrow dysfunction, neutropenia, hypersensitivity reactions, lupus-like syndrome, hypokalaemia, hyponatremia, hypochloraemia, hypomagnesaemia, hypercalcemia, hypocalcemia, hypovolemia, metabolic alkalosis, hyperglycemia, hyperuricemia, gout, hypercholesterolemia, hypertriglyceridaemia, sleep, depression, confusion, decreased tear secretion, blurred vision, yellow vision, arrhythmia, hypotension, interstitial pneumonitis, acute pulmonary edema, dry mouth, salivary gland inflammation, decreased appetite, pancreatitis, cholestatic jaundice, rash , hypersensitivity reactions to light, pseudoporphyria, vasculitis of the skin, muscle spasms, interstitial nephritis, renal dysfunction, impotence.

Orally. Adults: 1 tabl. once a day. The drug should be taken at approximately the same time every day; can be taken regardless of food intake. The tablets should not be chewed or crushed, they should be swallowed with water.