Lisinopril-OBL - instructions for use, dose, side effects, contraindications

lisinopril dihydrate 2.723 mg in terms of lisinopril 2.5 mg or lisinopril dihydrate 5.445 mg in terms of lisinopril 5 mg or lisinopril dihydrate 10.89 mg in terms of lisinopril 10 mg or lisinopril dihydrate 21.78 mg in terms of lisinopril 20 mg.

Excipients: lactose monohydrate, calcium hydrogen phosphate dihydrate, g silicon dioxide colloid (aerosil), microcrystalline cellulose, magnesium stearate, talc.

Description:Tablets are white, round, flat-faced with a facet (at a dosage of 2.5 mg) and risk (at a dosage of 10 mg) or biconvex, oblong with rounded edges, with a risk (with a dosage of 5 mg and 20 mg).

Pharmacotherapeutic group:Angiotensin-converting enzyme inhibitor (ACE)

ATX: & nbsp

C.09.A.A.03 Lisinopril

C.09.A.A ACE Inhibitors

Pharmacodynamics:

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 the overall peripheral vascular resistance, arterial pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and increased tolerance of the myocardium to loads 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, myocardial hypertrophy and the walls of arteries of resistive type decrease. 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 maximum effect is determined after 6-7 hours and persists for 24 hours. With arterial hypertension, the effect is observed in the first days after the start of treatment, stable action develops after 1-2 months. With a sharp withdrawal of the drug, no pronounced increase in blood pressure (BP) was observed.

In addition to reducing blood pressure lisinopril reduces albuminuria. Lisinopril does not affect the concentration of glucose in the blood in patients with diabetes mellitus and does not increase the incidence of hypoglycemia.

Pharmacokinetics:

Suction. After oral administration lisinopril absorbed; from the gastrointestinal tract (GIT) on average by 25%, but the absorption can vary from 6 to 60%., Bioavailability is 25%. Eating does not affect the absorption of the drug.

Distribution. Almost does not bind to blood plasma proteins. The maximum concentration in blood plasma of 90 ng / ml is reached in 7 hours. Permeability through the blood-brain and placental barrier is low.

Metabolism. Lizinopril is not biotransformed in the body.

Excretion. It is excreted by the kidneys unchanged. The half-life is 12 hours.

Pharmacokinetics in selected patient groups

In patients with chronic heart failure, the absorption and clearance of lisinopril are reduced, bioavailability is 16%.

In patients with renal insufficiency, the concentration of lisinopril is several times higher than the concentration in the blood plasma in healthy volunteers, with an increase in the time to reach the maximum concentration in the blood plasma and an increase in the half-life.

In elderly patients, the concentration of the drug in the blood plasma and the area under the "concentration-time" curve is 2 times greater than in young patients.

Indications:

- Arterial hypertension (in monotherapy or in combination with other antihypertensive agents);

- Chronic heart failure (as part of combination therapy for the treatment of patients taking cardiac glycosides and / or diuretics);

- Early treatment of acute myocardial infarction in combination therapy (in the first 24 hours with stable hemodynamic parameters to maintain these parameters and prevention of left ventricular dysfunction and heart failure);

Diabetic nephropathy (decreased albuminuria in insulin-dependent patients with normal blood pressure and non-insulin-dependent patients with hypertension).

Contraindications:

- Hypersensitivity to lisinopril and other components of the drug, as well as to other ACE inhibitors;

- angioedema in history, including the use of ACE inhibitors;

- Hereditary edema Quincke or idiopathic angioedema;

- age under 18 years (effectiveness and safety not established);

- simultaneous use with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus or violations of kidney function of moderate and / or severe severity (creatinine clearance (CK) less than 60 ml / min);

- lactose intolerance, lactase deficiency, glucose-galactose mal-absorption syndrome.

Carefully:Expressed violations of kidney function,bilateral renal artery stenosis or stenosis of the artery only kidneys with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia. aortic stenosis, hypertrophic obstructive cardiomyopathy, primary aldosteronism, hypotension, cerebrovascular diseases (including cerebrovascular insufficiency), ischemic heart disease, coronary insufficiency, autoimmune systemic diseases of connective tissue (including scleroderma. systemic lupus erythematosus ); oppression of bone marrow hematopoiesis; simultaneous use of ACE inhibitors with drugs containing aliskiren, or angiotensin II receptor antagonists (with double blockade of RAAS, there is an increased risk of arterial hypotension, hyperkalemia and renal failure); diabetes; diet with sodium restriction; hypovolemic conditions (including as a result of diarrhea, vomiting); elderly, hemodialysis vysokoprotochnyh using dialysis membranes with high permeability (AN695); the use of Negroid race in patients.

Pregnancy and lactation:

The use of Lysinocryl in pregnancy is contraindicated. When pregnancy is established, taking the drug Lisinopril you must stop as soon as possible. Admission of ACE inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (there may be a pronounced 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 case of application during the I trimester are not present. For newborns and infants who have undergone intrauterine exposure to ACE inhibitors, careful monitoring is recommended to timely detect a marked decrease in blood pressure, oliguria, and hyperkalemia.

Lysinocryl penetrates the placenta. There is no data on the isolation of lisinopril in breast milk. If the drug is taken Lisinopril it is necessary during lactation that breastfeeding should be abolished.

Dosing and Administration:

Inside, regardless of food intake, preferably at the same time.

When arterial hypertension patients who do not receive other antihypertensives are prescribed 5 mg once a day.In the absence of effect, the dose is increased every 2-3 days by 5 mg to an average therapeutic dose of 20-40 mg / day (increasing the dose above 40 mg / day usually does not lead to a further decrease in blood pressure). The usual daily maintenance dose is 20 mg.

The maximum daily dose is 40 mg.

The full effect usually develops in 2-4 weeks from the start of treatment, which should be taken into account when increasing the dose. With insufficient clinical effect, it is possible to combine the drug with other antihypertensive drugs.

If the patient received prior treatment with diuretics, the use of such drugs should be stopped 2-3 days before the drug is started Lisinopril. If this is not feasible, then the initial dose of the drug Lisinopril should not exceed 5 mg per day. In this case, after taking the first dose, medical supervision is recommended for several hours (maximum effect is achieved after about 6 hours), since there may be a pronounced decrease in blood pressure.

With Renovascular Hypertension or other conditions with increased activity of the renin-angiotensin-aldosterone system, it is also advisable to prescribe a low initial dose of 2.5-5 mg per day, under enhanced medical supervision (blood pressure control, kidney function, potassium ion content in blood serum).The maintenance dose, continuing strict medical control, should be determined depending on the dynamics of blood pressure.

With renal insufficiency, due to the fact that lisinopril is released through the kidneys, the initial dose should be determined depending on the creatinine clearance. Further, the choice of doses should be made depending on individual reactions with regular monitoring of kidney function, potassium level, sodium in the blood serum.

Creatinine clearance, ml / min	Initial dose of lisinopril, mg per day
30-70	5-10
10-30	2,5-5
less than 10	2,5

(including patients on hemodialysis)

With persistent arterial hypertension, prolonged maintenance therapy of 10-15 mg / day is shown.

With chronic heart failure - begin with 2.5 mg once a day, followed by an increase in the dose of 2.5 mg 3-5 days before the usual, maintaining a daily dose of 5-20 mg. The dose should not exceed 20 mg per day. In elderly patients, a more pronounced prolonged hypotensive effect is often observed, which is associated with a decrease in the rate of excretion of lisinopril (it is recommended to begin treatment with 2.5 mg / day).

Acute myocardial infarction (as part of combination therapy) - on the first day - 5 mg orally, then 5 mg every other day, 10 mg after two days and then 10 mg once a day. In patients with acute myocardial infarction, the drug should be applied for at least 6 weeks.

At the beginning of treatment or within the first 3 days after an acute myocardial infarction in patients with low systolic BP (120 mm Hg or lower), a smaller dose of 2.5 mg should be given. In the case of a decrease in blood pressure (systolic blood pressure is below or equal to 100 mm Hg), a daily dose of 5 mg can be reduced to 2.5 mg if necessary. In the case of a long pronounced decrease in blood pressure (systolic blood pressure below 90 mm Hg for more than 1 hour), treatment with the drug Lisinopril should be discontinued.

Diabetic Nephropathy - in patients with insulin-dependent diabetes mellitus, 10 mg of the drug Lisinopril 1 time per day. The dose may, if necessary, be increased to 20 mg once a day in order to achieve diastolic blood pressure values below 75 mm Hg in the "sitting" position.

In patients with insulin-dependent diabetes mellitus, the dose is the same, in order to achieve diastolic blood pressure values below 90 mm Hg. in the "sitting" position.

Side effects:

The incidence of unwanted reactions is presented according to the WHO classification: very often (≥1 / 10 cases), often (≥1 / 100 and <1/10 cases) infrequently (≥1 / 1000 and <1/100 cases), rarely (≥ 1/10000 and <1/1000 cases) and very rarely (<1/10000 cases).

The most common side effects are: dizziness, headache, fatigue, dry cough, nausea, diarrhea.

From the cardiovascular system: often - marked decrease in blood pressure, orthostatic hypotension; rarely - chest pain, tachycardia, bradycardia, aggravation of symptoms of chronic heart failure, violation of atrioventricular conduction, myocardial infarction.

From the central nervous system: often - paresthesia, lability of mood, confusion, drowsiness, convulsive twitching of the muscles of the limbs and lips; rarely - asthenic syndrome.

On the part of the hematopoiesis system: rarely - leukopenia, neutropenia. agranulocytosis, thrombocytopenia, with prolonged treatment - anemia (reduction of hemoglobin, hematocrit, erythrocytopenia).

From the respiratory system: rarely dyspepsia, bronchospasm.

Laboratory indicators: often - hyperkalemia, hyponatremia; infrequently - hyperbilirubinemia, increased activity of "hepatic" enzymes, hypercreatininaemia, increased concentrations of urea and creatinine; very rarely - a decrease in the concentration of glucose in the blood.

From the digestive system: rarely - dryness of the oral mucosa, dyspepsia, changes in taste, anorexia, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

From the skin: rarely - urticaria, increased sweating, pruritus, alopecia, photosensitivity; very rarely - pseudolymphoma of the skin.

From the genitourinary system: rarely - a violation of kidney function, oliguria, anuria, acute renal failure, uremia, proteinuria, decreased potency.

Allergic reactions: rarely angioedema, swelling of the face, limbs, lips, tongue, epiglottis and / or larynx, skin rashes, itchy skin, fever, positive antinuclear antibody test results, increased erythrocyte sedimentation rate (ESR), eosinophilia, leukocytosis. In very rare cases, an intestinal angioedema.

Other: rarely - myalgia, arthralgia / arthritis, vasculitis.

Overdose:

Symptoms (occur when taking a single dose of 50 mg): a marked decrease in blood pressure, dryness of the oral mucosa, drowsiness, urinary retention, constipation, anxiety, increased irritability.

Treatment: there is no specific antidote. Gastric lavage, application of enterosorbents and laxatives. Intravenous introduction of 0.9% sodium chloride solution was shown. In the case of a sustained bradycardia, the use of an artificial pacemaker is necessary. It is necessary to monitor blood pressure, indicators of water-electrolyte balance. Hemodialysis is effective.

Interaction:

With the simultaneous use of the drug with potassium-sparing diuretics (spironolactone, triamterene. amyloride), potassium preparations, salt substitutes containing potassium, cyclosporine, increases the risk of hyperkalemia, especially with impaired renal function, so they can be jointly administered only with regular monitoring of potassium ion content in the blood serum and kidney function.

The combined use of lisinopril with beta-blockers, slow calcium channel blockers (BCCI), diuretics, tricyclic antidepressants / neuroleptics and other antihypertensive drugs increases the severity of hypotensive action.

Lizinopril slows down the excretion of lithium preparations.Therefore, when combined, it is necessary to regularly monitor the concentration of lithium in the blood serum.

Antacids and colestramine reduce the absorption of lisinopril in the gastrointestinal tract.

When combined with insulin and hypoglycemic agents for oral administration, there is a risk of developing hypoglycemia.

Non-steroidal anti-inflammatory drugs (NSAIDs) (including selective inhibitors of cyclooxygenase-2 (COX-2)), estrogens, adrenostimulants reduce the hypotensive effect of lisinopril.

With the simultaneous use of inhibitors of ACE and gold preparations intravenously (sodium aurotomy malate) describes a symptom complex, which includes facial flushing, nausea, vomiting and lowering blood pressure.

When combined with selective serotonin reuptake inhibitors, it can lead to severe hyponatraemia. Joint application with allopurinol, procainamide, cytostatics can lead to leukopenia. Contraindicated simultaneous use of ACE inhibitors with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus or violations of the kidneys of moderate and / or severe severity (creatinine clearance (CC) less than 60 ml / min).In elderly patients and patients with impaired renal function, simultaneous administration of ACE inhibitors with sulfamethoxazole / trimethoprim was accompanied by severe hyperkalemia, which is believed to be caused by trimethoprim, so the drug should be used with caution with preparations containing trimethoprim regularly monitoring the potassium content in the blood plasma. Simultaneous use of ACE inhibitors and inhibitors of the mTOR kinase enzyme (mammalian rapamycin target), for example tessirolimus, sirolimus, everolimus may be accompanied by an increased risk of angioedema.

Special instructions:

Symptomatic hypotension

Most often, a marked decrease in blood pressure occurs with a decrease in the volume of circulating blood (BCC), caused by diuretic therapy, a decrease in salt in the diet, dialysis, diarrhea, or vomiting. In patients with chronic heart failure with concurrent renal failure or without it, a marked decrease in blood pressure is possible.

Under the strict supervision of a physician, Lisinopril patients with coronary artery disease, cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or to a stroke.Transient arterial hypotension is not a contraindication for taking the next dose of the drug.

When using the drug Lisinopril, in some patients with chronic heart failure, but with normal or low blood pressure, there may be a decrease in blood pressure, which is usually not a reason for stopping treatment.

Before the start of treatment with the drug, if possible, the sodium content should be normalized and / or replenished with BCC. carefully monitor the effect of the initial dose of the drug Lisinopril on the patient.

With bilateral renal artery stenosis and renal artery stenosis of a single kidney, as well as with hyponatremia and / or a decrease in the volume of circulating blood (BCC) or circulatory insufficiency, arterial hypotension caused by taking the drug Lisinopril, can lead to a decrease in kidney function with the subsequent development of reversible (after discontinuation of the drug) acute renal failure.

Data on the use of the drug Lisinopril in patients after kidney transplantation there are no kidneys.

With acute myocardial infarction

The use of standard therapy (thrombolytics, acetylsalicylic acid, beta-blockers). Lisinopril it is possible to use together with intravenous administration or with the use of therapeutic transdermal systems of nitroglycerin.

Stenosis of the aortic estuary / hypertrophic obstructive cardiomyopathy

Lizinopril, like other ACE inhibitors, should be administered with caution to patients with obstruction of the left ventricular outflow tract (stenosis of the aortic estuary, hypertrophic obstructive cardiomyopathy).

Hyperkalemia

During treatment with ACE inhibitors, including lisinopril, hyperkalemia may develop. Risk factors for hyperkalemia include renal failure (eg, diabetic nephropathy), advanced age, diabetes mellitus, certain concomitant conditions (decreased BCC, acute heart failure in decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), as well as preparations of potassium or potassium-containing salt substitutes and the use of other drugs that increase the level of potassium in the blood plasma (for example, heparin).If it is necessary to simultaneously take the above drugs, you need to monitor the potassium content in the blood serum.

Surgery / general anesthesia

With extensive surgical interventions, as well as with the use of other means that cause a decrease in blood pressure, Lisinopril, blocking the formation of angiotensin II, can cause a pronounced unpredictable decrease in blood pressure.

Hypoglycemic drugs

With the simultaneous use of ACE inhibitors and insulin, as well as hypoglycemic drugs for oral administration, hypoglycemia may develop. The greatest risk of development of hypoglycemia is observed during the first two weeks of combined therapy, as well as in patients with renal impairment. Patients with diabetes require careful monitoring of the glycemic profile, especially during the first month of therapy.

In elderly patients, the same dose leads to a higher concentration of the drug in the blood, therefore special caution is required when determining the dose.

Because the potential risk of agranulocytosis can not be ruled out, periodic monitoring of the blood picture is required.

When using the drug in dialysis with polyacryl-nitrile membranes, anaphylactic shock can occur. therefore, either a different type of membrane for dialysis or the prescription of other antihypertensive agents is recommended.

Double blockade of RAAS

Arterial hypotension, fainting, stroke, hyperkalemia and renal dysfunction (including acute renal failure) have been reported in susceptible patients, especially when used with medications that affect this system. Therefore, a double blockade of RAAS due to a combination of an ACE inhibitor with ARA II or aliskiren is not recommended.

Hypersensitivity / angioedema

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. In this case, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without a previous angioedema and at a normal level of C-1-esterase. The diagnosis is established by means of computed tomography of the abdominal cavity, ultrasound examination or at the time of surgical intervention.Symptoms disappear after the cessation of the use of ACE inhibitors. In patients with abdominal pain taking ACE inhibitors, the differential diagnosis should take into account the possibility of angioedema edema development.

Neutropenia, agranulocytosis, thrombocytopenia, anemia

Against the background of taking ACE inhibitors, neutropenia, agranulocytosis, thrombocytopenia and anemia can occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia develops rarely. With special care, lisino-pril should be used in patients with systemic connective tissue diseases, when immunosuppressants, allopurino-l or procainamide are used, especially in patients with impaired renal function.

Ethnic differences

Lizinopril and other ACE inhibitors are less effective in patients of the Negroid race, due to the prevalence of patients with hypertension with low renin activity. In patients of the Negroid race angioneurotic edema with lisinopril is more common than in patients of other races.

Effect on the ability to drive transp. cf. and fur:There is no evidence of the effect of Lysino-pril on the ability to drive vehicles and mechanisms, applied in therapeutic doses, but it must be taken into account that dizziness and drowsiness may occur, therefore, care must be taken.

Form release / dosage:Tablets of 2.5 mg, 5 mg, 10 mg and 20 mg.

Packaging:

For 10, 15, 20, 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 1, 2, 3, 4, 5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-004403/10

Date of registration:18.05.2010 / 23.03.2016

Expiration Date:Unlimited

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Information update date: & nbsp25.02.2018

Illustrated instructions

Instructions

Lisinopril-OBL (Lisinopril-OBL)