Composition, form of production and packaging
Tablets are light blue with a few impregnations of a darker color, round, plane-cylindrical, with a facet, with engraving "C43" on one side.
1 tab.
lisinopril dihydrate 10.89 mg,
which corresponds to the content of lisinopril 10 mg
hydrochlorothiazide 12.5 mg
Auxiliary substances: mannitol - 50 mg, aluminum lacquer based on indigotine dye (E132) 0.2 mg, pregelatinized starch 2.25 mg, corn starch 31 mg, calcium hydrogen phosphate dihydrate 136.8 mg, partially pregelatinized calcium starch 2.25 mg, magnesium stearate - 5 mg.
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
Tablets of light green color with a few impregnations of a darker color, round, plane-cylindrical, with a facet, with engraving "C44" on one side.
1 tab.
lisinopril dihydrate 21.77 mg,
which corresponds to the content of lisinopril 20 mg
hydrochlorothiazide 12.5 mg
Auxiliary substances: mannitol - 50 mg, lacquer aluminum based on the dye of indigotine (E132) 0.2 mg, iron dye oxide yellow (E172) 0.1 mg, pregelatinized starch 2.25 mg, corn starch 31 mg, calcium hydrogen phosphate dihydrate 136.7 mg , partially pregelatinized starch - 2.25 mg, magnesium stearate - 5 mg.
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Antihypertensive drug. Has antihypertensive and diuretic effect.
Lisinopril
The ACE inhibitor reduces the formation of angiotensin II from angiotensin I. Reducing angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces OPSS, AD, preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and increased tolerance to stress in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by the effect on tissue renin-angiotensin systems. With prolonged use, the severity of myocardial hypertrophy and the walls of arteries of resistive type decreases. Improves the blood supply of the ischemic myocardium.
ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients who underwent myocardial infarction without clinical manifestations of heart failure. The antihypertensive effect begins in about 6 hours and persists for 24 hours. The duration of the effect also depends on the amount of the dose. The onset of action is after 1 hour. The maximum effect is determined after 6-7 hours. With arterial hypertension, the effect is observed in the first days after the start of treatment, stable effect develops in 1-2 months.
With a sharp withdrawal of the drug, there is no pronounced increase in blood pressure.
In addition to reducing blood pressure, lisinopril reduces albuminuria. In patients with hyperglycemia contributes to the normalization of the function of the damaged glomerular endothelium.
Lizinopril does not affect the concentration of glucose in the blood in patients with diabetes mellitus and does not increase the incidence of hypoglycemia.
Hydrochlorothiazide
A thiazide diuretic whose diuretic effect is associated with a disruption of the reabsorption of sodium, chlorine, potassium, magnesium, water in the distal nephron;delays the excretion of calcium ions, uric acid. Has antihypertensive properties; the hypotensive effect develops due to the expansion of arterioles. Virtually no effect on normal blood pressure.
The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours and persists for 6-12 hours. Antihypertensive effect occurs in 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.
Lizinopril and hydrochlorothiazide, if used simultaneously, have an additive antihypertensive effect.
PHARMACOKINETICS
Lysinopril. After taking lisinopril, C max in the blood serum is reached after 7 hours. It weakly binds to plasma proteins. The average degree of absorption of lisinopril is about 25%, with a significant interindividual variability (6-60%). Food does not affect the absorption of lisinopril. Lizinopril is not metabolized and is excreted unchanged only by the kidneys. After repeated administration, the effective T 1/2 of lisinopril is 12 hours. Impaired renal function slows the excretion of lisinopril, but this slowing becomes clinically significant only when the glomerular filtration rate decreases below 30 mL / min. In elderly patients, an average of 2 times the level of the maximum concentration of the drug in the blood and AUC, compared with patients of a younger age. Lizinopril is excreted from the body by hemodialysis.
It penetrates to a small extent through the BBB.
Hydrochlorothiazide is not metabolized, but is rapidly eliminated through the kidneys. T 1/2 of the drug ranges from 5.6 to 14.8 hours. At least 61% of the ingested drug is excreted unchanged for 24 hours. Hydrochlorothiazide penetrates the placental barrier, but does not penetrate the BBB.
INDICATIONS
- Arterial hypertension (in patients who are shown combined therapy).
DOSING MODE
Assign inside 1 tab. 1 time / day. If the proper therapeutic effect is not achieved within 2-4 weeks, the dose of the drug can be increased to 2 tab. 1 time / day.
In patients with KK 30-80 ml / min the drug can be used only after selecting the dose of individual components of the drug. The recommended initial dose of lisinopril in uncomplicated renal failure is 5-10 mg.
Symptomatic arterial hypotension can occur after taking the initial dose of the drug. Such cases are more common in patients who have had a loss of fluid and electrolytes due to previous treatment with diuretics. Therefore, you should stop taking diuretics 2-3 days before starting treatment with the drug.
SIDE EFFECT
The most common side effects: dizziness, headache.
From the cardiovascular system: a marked decrease in blood pressure, chest pain; rarely - orthostatic hypotension, tachycardia, bradycardia, the appearance of symptoms of heart failure, violation of AV-conduction, myocardial infarction.
On the part of the digestive system: nausea, vomiting, abdominal pain, dry mouth, diarrhea, dyspepsia, anorexia, taste change, pancreatitis, hepatitis (hepatocellular and cholestatic), jaundice.
From the skin: urticaria, increased sweating, photosensitivity, skin itching, hair loss.
From the side of the central nervous system: lability of mood, violation of concentration, paresthesia, increased fatigue, drowsiness, convulsive twitching of the muscles of the extremities and lips; rarely - asthenic syndrome, confusion.
On the part of the respiratory system: dyspnoea, dry cough, bronchospasm, apnea.
On the part of the hematopoiesis system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decrease in hemoglobin concentration, hematocrit, erythrocytopenia).
Allergic reactions: angioedema, facial, extremities, lips, tongue, epiglottis and / or larynx, skin rashes, itching, fever, vasculitis, positive reactions to antinuclear antibodies, increased ESR, eosinophilia.
On the part of the genitourinary system: uremia, oliguria / anuria, impaired renal function, acute renal failure, decreased potency.
Laboratory indicators: hyperkalemia and / or hypokalemia, hyponatremia, hypomagnesemia, hypochloraemia, hypercalcemia, hyperuricemia, hyperglycemia, increased urea and creatinine levels in the blood plasma, hyperbilirubinemia, hypercholesterolemia, hypertriglyceridemia, decreased glucose tolerance, increased hepatic transaminase activity, especially when present in the anamnesis of kidney disease, diabetes mellitus, and renovascular hypertension.
Other: arthralgia, arthritis, myalgia, fever, impaired fetal development, exacerbation of gout.
CONTRAINDICATIONS
- angioedema (including Quincke's swelling in the anamnesis associated with the use of ACE inhibitors);
anuria;
- marked renal failure (CC less than 30 ml / min);
- hemodialysis using high-flow membranes;
- hypercalcemia;
- hyponatremia;
- porphyria;
- Prekoma;
- hepatic coma;
- severe forms of diabetes mellitus;
- age under 18 years (efficiency and safety not established);
- hypersensitivity to lisinopril, other ACE inhibitors or hydrochlorothiazide and excipients.
With caution: aortic stenosis / hypertrophic cardiomyopathy, bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney with progressive azotemia, condition after kidney transplantation, renal failure (QC more than 30 ml / min), primary hyperaldosteronism, hypotension, bone marrow hypoplasia, hyponatremia an increased risk of developing arterial hypotension in patients on a low-salt or salt-free diet), hypovolemic conditions (including diarrhea, vomiting), connective disorders (including systemic lupus erythematosus, scleroderma), diabetes mellitus, gout, oppression of bone marrow hematopoiesis, hyperuricemia, hyperkalemia, IHD, cerebrovascular diseases (including cerebral circulatory insufficiency), severe chronic heart failure, hepatic insufficiency , elderly age.
PREGNANCY AND LACTATION
The use of lisinopril during pregnancy is contraindicated. When establishing a pregnancy, the drug should be stopped as soon as possible. Admission of ACE inhibitors in the II and III trimesters of pregnancy has an adverse effect on the fetus (there may be a marked decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, fetal death). Data on the negative effects of the drug on the fetus in the case of application in the I trimester is not. For newborns and infants who have undergone intrauterine exposure to ACE inhibitors, it is recommended to monitor for the timely detection of a marked decrease in blood pressure, oliguria, and hyperkalemia.
During the treatment, the drug should be abolished breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in severe renal failure (QC less than 30 ml / min), a condition after kidney transplantation.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution: liver failure.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
APPLICATION IN ELDERLY PATIENTS
With caution: the elderly.
SPECIAL INSTRUCTIONS
Most often, a marked decrease in blood pressure occurs with a decrease in fluid volume caused by diuretic therapy, a decrease in the amount of salt in the food, dialysis, diarrhea, or vomiting.
In patients with chronic heart failure with simultaneous renal insufficiency or without it, a marked decrease in blood pressure is possible. It is more often detected in patients with a severe class of chronic heart failure, as a result of the use of large doses of diuretics, hyponatremia or impaired renal function. In such patients, treatment should begin under the strict supervision of a physician. Similar rules should be adhered to in the appointment of patients with IHD, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.
Transient arterial hypotension is not a contraindication for further administration of the drug.
Before the start of treatment, if possible, the sodium concentration should be normalized and / or replace the lost volume of fluid, carefully monitor the effect of the initial dose of the drug on the patient.
In patients with chronic heart failure, a marked decrease in blood pressure after initiation of treatment with ACE inhibitors may lead to further deterioration of renal function. Cases of acute renal failure are noted.
In patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney receiving ACE inhibitors, there was an increase in urea and serum creatinine, usually reversible after discontinuation of treatment. It was more common in patients with renal insufficiency.
Angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx was rarely seen in patients treated with ACE inhibitors, including lisinopril, which may occur at any time of treatment. In this case, treatment with lisinopril should be stopped as soon as possible and for the patient to establish an observation until the symptoms regress completely. In cases where there was only edema of the face and lips, the condition usually passes without treatment, however, it is possible to prescribe antihistamines. Angioedema with edema of the larynx can be fatal. When the tongue, epiglottis or larynx are covered, airway obstruction may occur, so an appropriate therapy (0.3-0.5 ml epinephrine (adrenaline) 1: 1000 p / c) should be taken immediately and / or measures to ensure airway patency.
Patients who have had a history of angioedema, not associated with previous treatment with ACE inhibitors, may have an increased risk of developing it during treatment with an ACE inhibitor.
When an ACE inhibitor was used, a cough was noted. Cough is dry, prolonged, which disappears after discontinuing treatment with an ACE inhibitor. With a differential diagnosis of cough, one must also consider a cough caused by the use of an ACE inhibitor.
Anaphylactic reaction was noted in patients undergoing hemodialysis using dialysis membranes with high permeability (AN69 В® ), which simultaneously take ACE inhibitors. In such cases, one should consider the possibility of using another type of membrane for dialysis or another antihypertensive agent.
When using drugs that reduce blood pressure in patients with extensive surgery or during general anesthesia, lisinopril may block the formation of angiotensin II.
The pronounced decrease in blood pressure, which is considered a consequence of this mechanism, can be eliminated by an increase in BCC.
Before surgery (including dentistry), an anesthesiologist should be warned about the use of ACE inhibitors.
In some cases, hyperkalemia was noted. Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, the use of potassium drugs or drugs that cause an increase in the potassium concentration in the blood (eg, heparin), especially in patients with impaired renal function.
In patients who have a risk of symptomatic hypotension (on a low-salt or salt-free diet) with or without hyponatremia, as well as in patients who received high doses of diuretics, the above conditions must be compensated before the start of treatment (loss of fluid and salts).
Thiazide diuretics can influence glucose tolerance, so you need to adjust the dose of hypoglycemic agents for oral administration. Thiazide diuretics can reduce the secretion of calcium by the kidneys and cause hypercalcemia. Expressed hypercalcemia may be a symptom of latent hyperparathyroidism. It is recommended to stop treatment with thiazide diuretics before the parathyroid gland function test.
During the treatment with the drug, regular monitoring of the blood plasma of potassium, glucose, urea, lipids is required.
During the period of treatment it is not recommended to drink alcoholic beverages. Ethanol enhances the hypotensive effect of the drug.
Care should be taken when performing physical exercises, hot weather (the risk of dehydration and excessive blood pressure lowering due to a decrease in BCC).
Impact on the ability to drive vehicles and manage mechanisms
During the treatment period, one should refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, possibly dizziness, especially at the beginning of the course of treatment.
OVERDOSE
Symptoms: marked decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, increased irritability.
Treatment: symptomatic therapy, intravenous fluids, blood pressure control; therapy aimed at correcting dehydration and violations of the water-salt balance. Control of urea, creatinine and electrolytes in blood serum, as well as diuresis.
DRUG INTERACTION
With simultaneous use with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium, the risk of hyperkalemia increases, especially in patients with impaired renal function. Therefore, they can be jointly administered only on the basis of an individual decision of the physician with regular monitoring of potassium level in the serum and kidney function.
With simultaneous use with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol, increased antihypertensive effect.
With simultaneous use with NSAIDs (indomethacin and others), estrogens, there is a decrease in the antihypertensive effect of lisinopril.
With simultaneous use with lithium preparations, lithium removal from the body slows down (increased cardiotoxic and neurotoxic action of lithium).
With simultaneous use with antacids and colestyramin, absorption in the digestive tract decreases.
The preparation enhances the neurotoxicity salicylates, reduces the effect of hypoglycemic agents for oral administration, norepinephrine, epinephrine and protivopodagricakih preparations enhances the effects (including spin), cardiac glycosides, peripheral muscle relaxant effect, reduces the excretion of quinidine.
Reduces the effect of oral contraceptives.
Ethanol enhances the hypotensive effect of the drug.
At the same time taking methyldopa increased risk of hemolysis.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of reach of children at a temperature not higher than 30 В° C. Shelf life - 3 years.
