Index of drugs

Mild to moderate hypertension in patients in whom treatment with individual active substances in the same doses, in separate medicines, allowed to control blood pressure.

1 tabl contains: 10 mg lisinopril (as lisin lisinopril) and 12.5 mg hydrochothotiazide or 20 mg lisinopril (as lisin lisinopril) and 12.5 mg hydroquinothiazide or 20 mg lisinopril (as lisinopril dihydrate) and 25 mg hydrochlorothiazide.

Combined preparation containing an angiotensin converting enzyme inhibitor (lisinopril) and a diuretic (hydrochlorothiazide). The antihypertensive effect of both of these active substances is mutually complementary and almost additive, while the loss of potassium caused by hydrochlorothiazide is reduced under the influence of lisinopril. Inhibition of ACE by lisinopril results in a decrease in angiotensin II concentration in the blood plasma and a reduction in aldosterone secretion, which may be the cause of increased serum potassium. The mechanism of action of lisinopril is mainly related to the inhibition of the renin-angiotensin-aldosterone system, but it also has antihypertensive effect in patients with low-renin hypertension. Lisinopril can also block the distribution of bradykinin. Hydrochlorothiazide is a thiazide diuretic. It works directly on the kidneys by increasing the excretion of NaCl and following water. In the initial section of the distal tubule of the nephron, the drug inhibits the transport of neutral electric NaCl in the lumen of the cell membrane. The elimination of potassium and Magnesium increases and Calcium decreases. Hydrochlorothiazide causes slight excretion of bicarbonates, and chloride excretion is greater than sodium excretion. Hydrochloric acidosis may occur during treatment with hydrochlorothiazide. Hydrochlorothiazide is actively excreted in the proximal tubule. The diuretic effect is maintained in acidosis or metabolic alkalosis. As possible mechanisms of antihypertensive effect of hydrochlorothiazide, changes in sodium balance, decrease in blood plasma volume and extracellular fluid, changes in renal vascular resistance and reduced susceptibility to noradrenaline and angiotensin II are considered. Elimination of electrolytes and water under the influence of hydrochlorothiazide begins after 2 hours, is the greatest after 3-6 h and persists for 6-12 h. Antihypertensive effect appears for the first time after 3-4 days and may persist up to 1 week after discontinuation of treatment. Co-administration of lisinopril and hydrochlorothiazide has no effect on the bioavailability of any of these substances. A compound dose containing lisinopril and hydrochlorothiazide has bioequivalence to be administered in separate medicines. After oral administration, maximum serum concentrations of lisinopril occur after approx. 7 hours. Effective T_0,5 lisinopril in the accumulation phase, after repeated administration is 12.6 h. The average absorption of lisinopril is about 25% of the adopted dose (range 6-60%). Lisinopril is not metabolised in the body and is excreted unchanged by the kidneys. It can be removed by dialysis. After oral administration, hydrochlorothiazide is absorbed in the gastrointestinal tract at approximately 80%. System availability is 71 ± 15%. The degree of binding to plasma proteins is 65%. In healthy people, it is excreted in over 95% in unchanged form by the kidneys. T_0,5 is 2.5 hours for normal kidney function. Maximum plasma concentration occurs after 2-5 h; It is prolonged in the case of kidney dysfunction and is about 20 hours in patients with end stage renal disease. The diuretic effect occurs within 1-2 h, persists for 10-12 h depending on the dose, the antihypertensive effect persists for 24 hours.

Hypersensitivity to active substances, any other ACE inhibitor or sulfonamides (possible cross-reactivity), or to any of the excipients. Angioneurotic edema associated with previous treatment with an ACE inhibitor. Hereditary or idiopathic angioneurotic edema. Haemodynamically significant aortic valve stenosis or mitral valve or hypertrophic cardiomyopathy.Severe renal impairment (creatinine clearance <30ml / min) and end-stage renal disease. Severe hepatic failure. II and III trimester of pregnancy, breastfeeding period. Public gout. Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²).

lisinopril. Patients with an increased risk of symptomatic hypotension (eg after treatment with diuretics, when using a salt-restricted diet, dialyzotherapy, diarrhea or vomiting, or if there is severe renin-dependent hypertension), and patients with heart failure should be closely monitored when starting treatment and increasing the dose. Similar recommendations apply to patients with ischemic heart disease and cerebrovascular disorders in which a significant reduction in blood pressure may result in a myocardial infarction or cerebrovascular accident. The occurrence of transient hypotension is not a contraindication to the use of further doses, which can usually be given without difficulty, if the blood pressure increases after supplementing the intravascular volume. Do not start treatment with lisinopril in patients with acute myocardial infarction. Lisinopril should be used with caution in patients with narrowing of the left ventricle outflow pathway. In patients with impaired renal function, the starting dose of lisinopril should be adjusted and serum potassium and creatinine should be monitored regularly. In patients with heart failure, hypotension that occurs after initiation of ACE inhibitor therapy may cause further deterioration of renal function. In some patients with bilateral renal artery stenosis or artery stenosis of the sole active kidney who have been treated with ACE inhibitors, increases in urea and serum creatinine, usually resolving after discontinuation of treatment, have been reported. This is most likely in patients with renal failure. In the case of coexistence of renal arterial hypertension, there is an increased risk of severe hypotension and renal failure. In these patients, treatment should be started under close medical supervision. Diuretics should be discontinued and renal function monitored for the first few weeks of treatment with lisinopril. In some hypertensive patients without co-existing renal vascular disease, there was an increase in serum urea and creatinine, usually insignificant and transient, especially when lisinopril was used concomitantly with diuretics. This is more likely in patients with co-existing kidney problems. It may be necessary to reduce the dose and / or discontinue diuretic and / or ACE inhibitor. Due to lack of experience, the administration of lisinopril in patients after kidney transplantation is not recommended. ACE inhibitors are more likely to cause angioneurotic edema in black patients compared to patients of other breeds; lisinopril may be less effective in lowering blood pressure in black patients. In patients with a history of angioneurotic edema, which is unrelated to the use of ACE inhibitors, there is an increased risk of angioneurotic edema during therapy with an ACE inhibitor. It is not recommended for patients undergoing dialysis for renal failure. In dialysis patients with high permeability dialysis membranes (eg AN 69) and simultaneously using an ACE inhibitor, anaphylactoid reactions have been reported - consideration should be given to using other type of dialysis membranes or an antihypertensive drug from another group. In patients receiving ACE inhibitors during LDL apheresis with dextran sulphate, life-threatening anaphylactic reactions have rarely occurred - the ACE inhibitor should be temporarily discontinued prior to each apheresis. In patients taking ACE inhibitors during desensitisation (eg Hymenoptera venom), anaphylactoid reactions have occurred; these reactions did not occur when ACE inhibitors were temporarily discontinued but recurrent when the drug was accidentally re-applied. In patients who develop jaundice or increase in liver enzymes, treatment with lisinopril should be discontinued and appropriate measures should be taken. During therapy, there is a risk of neutropenia or agranulocytosis, thrombocytopenia and anemia.Lisinopril should be used with extreme caution in patients with vascular collagen, using immunosuppressants, taking Allopurinol or procainamide, and in patients who have these co-morbidities, especially if coexisting with renal function. When using lisinopril in patients who develop severe infections, it is recommended that the amount of leucocytes in the blood is regularly monitored and patients should be informed to report any signs of infection. The drug may be less effective in lowering blood pressure in black patients than in patients of other breeds. In patients undergoing major surgery or during anesthesia with antihypertensive agents, lisinopril may inhibit the formation of angiotensin II, secondary to the compensatory release of renin. If hypotension occurs, which is presumably the result of such action, increase the intravascular volume. In patients with an increased risk of hyperkalemia (with renal insufficiency or diabetes, using potassium sparing diuretics, potassium supplements or potassium-containing salt substitutes, other drugs increasing serum potassium, eg heparin), regular monitoring of potassium levels is recommended. In diabetic patients treated with oral antidiabetic agents or insulin, the blood Glucose should be monitored frequently during the first month of use and in patients with impaired renal function. The simultaneous use of ACE inhibitors with lithium should be avoided. 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.hydrochlorothiazide. In patients with kidney disease, thiazide diuretics can cause azotemia, drug accumulation can occur - if progressive renal failure appears, as indicated by an increase in non-protein nitrogen, treatment should be reconsidered, possibly with discontinuation of the diuretic. In patients with hepatic impairment or progressive liver disease, the drug should be used with caution due to the risk of hepatic coma. Thiazide diuretic therapy may reduce glucose tolerance - adjustment of insulin dose or oral hypoglycaemic agents may be required. During treatment with thiazide diuretics, latent diabetes may occur. In patients with liver cirrhosis, severe diuresis, insufficient oral supply of electrolytes, and patients treated concomitantly with corticosteroids or ACTH, there is an increased risk of hypokalaemia. During the high air temperature in patients with edema, hyponatraemia may occur with dilution (usually no treatment required). The drug may reduce the excretion of calcium in the urine and cause a transient and slight increase in serum Calcium, even if calcium metabolism is not disturbed. Significant hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazide diuretics increase the excretion of magnesium in the urine, which can lead to hypomagnesaemia. It is not recommended for use in children and adolescents under 18 years due to a lack of data on safety and efficacy.

The drug is contraindicated in the second and third trimester of pregnancy; use in the first trimester of pregnancy is not recommended. Do not use during breast-feeding.

Lisinopril.Common: increased alacycline phosphatase, increased bilirubin, increased LDL, increased transaminases, tachycardia, central dizziness, headache, cough, vomiting, diarrhea, nausea, rash, dermatitis, hypotension or orthostatic, cage pain thoracic (not associated with the heart), weakness, angioneurotic edema.Uncommon: increase in urea and serum creatinine, hyperkalemia, transient decrease in hemoglobin, decrease in hematocrit, cardiac arrest, myocardial infarction, arrhythmia, conduction disturbance, angina pectoris, palpitations, stroke, cerebrovascular incident, paresthesia, drowsiness, taste disturbances, tremors, sleep disorders, blurred vision, ear pain, tinnitus, diarrheal headache, dyspnoea, tracheitis and bronchitis, sinusitis, rhinitis, constipation, dry mouth, bloating with gas donation, renal failure, proteinuria, excessive sweating, pruritus, urticaria, muscle pain, weight gain, gout, shock, hypertension, transient ischaemia, sexual dysfunction, decreased appetite, depression, confusion. Rare: slight increases in hemoglobin, hyponatraemia, eosinophilia, leukopenia, neutropenia, transient anemia, thrombocytopenia, lymphadenopathy, dysphasia, memory problems, confusion, bronchospasm, pneumonia, pulmonary congestion, epistaxis, laryngitis / hoarseness, pancreatitis, inflammatory changes in the mouth, swollen tongue, swallowing disorders, prostate disorders, ecchymosis, arthritis, flushing (especially the face), hemorrhage, peripheral vascular disorders, weakness of one limb, hepatitis. Very rare: agranulocytosis, angioedema of the intestines, (partial) intestinal obstruction, acute renal failure, liver failure. A syndrome that may include one or more of the symptoms: fever, vasculitis, arthralgia / arthritis, positive anti-nuclear titer (ANA), accelerated ESR, eosinophilia and leukocytosis, rash, photosensitivity, other dermatological symptoms have been reported.hydrochlorothiazide. Very common: hyperglycemia, glycosuria, hyperuricaemia, electrolyte disturbances (including hyponatraemia and hypokalaemia), increased cholesterol and triglycerides. Common: transient concentrations of substances usually excreted in the urine (creatinine, urea, uric acid), palpitations, dizziness and headache, pancreatitis, irritation of the gastric mucosa, diarrhea, constipation, orthostatic hypotension, weakness. Uncommon: yellow vision, transient blurred vision, breathing disorders (including pneumonia and pulmonary edema), interstitial nephritis, hypersensitivity reactions to light, rash, urticaria, fever, jaundice (intrahepatic cholestatic jaundice), loss of appetite, anorexia. Rare: leukopenia, neutropenia, arrhythmia, agranulocytosis, thrombocytopenia, aplastic and hemolytic, bone marrow suppression, paraesthesia, renal dysfunction, toxic epidermal necrolysis, reactions similar to cutaneous lupus erythematosus, activation of cutaneous lupus erythematosus, muscle spasms, necrotizing vasculitis (vasculitis, cutaneous vasculitis), anaphylactic reactions, depression, anxiety, and sleep disorders. Not known: vertigo, metabolic alkalosis.

Orally. A compound medicine is not suitable for starting treatment. It is recommended to adjust the dose of individual active substances separately. Adults: the usual dose is 1 tablet. once a day. If the desired reaction is not achieved within 2-4 weeks, the dose may be increased to 2 tablets. once a day. Treatment can be continued without time limits depending on the clinical response, unless there are side effects.
After the first dose, especially in dehydrated and / or electrolyte depleted patients as a result of prior diuretic therapy, symptomatic hypotension may occur; diuretics should be discontinued 2-3 days before starting treatment with the preparation; if possible, start with the use of small doses of individual components (lisinopril 5 mg).Special groups of patients. In patients with impaired renal function (creatinine clearance> 30 ml / min and <80 ml / min) the dose should be adjusted with particular care (gradual increase in the dose of individual active substances). Do not use the preparation in the initial treatment of patients with renal insufficiency.Way of giving. The drug should be taken every day at the same time.