Lizinopril - instructions for use, dose, side effects, contraindications

Excipients - mannitol 15mg / 30mg / 60mg, corn starch 36mg / 72mg / 144mg, calcium hydrophosphate dihydrate 30mg / 60mg / 120mg, sodium carboxymethyl starch 3mg / 6mg / 12mg, magnesium stearate 1mg / 2mg / 4mg, microcrystalline cellulose 10mg / 20mg / 40mg.

Description:

Tablets 5 mg and 10 mg. Tablets are white or almost white in color, flat-cylindrical, with a bevel.

Tablets 20 mg. Tablets are white or almost white in color, flat-cylindrical, with a facet and a risk.

Pharmacotherapeutic group:Angiotensin-converting enzyme (ACE) inhibitor

ATX: & nbsp

C.09.A.A.03 Lisinopril

C.09.A.A ACE Inhibitors

Pharmacodynamics:

ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. Reducing the content of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Inhibits tissue renin-angiotensin-aldosterone system, incl. vascular wall. As a consequence, blood pressure (BP) decreases, the total peripheral resistance of the vessels, preload, pressure in the pulmonary capillaries; the minute volume of blood increases, in patients with chronic heart failure, the tolerance of the myocardium to exercise increases. Lisinopril expands arteries more than veins. The antihypertensive effect begins to develop after 1 hour, reaching a maximum after 6-7 hours, and persists for 24 hours. With arterial hypertension, the effect is observed in the first days of treatment, stable after 1-2 months.With a sharp withdrawal of the drug marked increase in blood pressure is not observed.

Lizinopril reduces albuminuria. In patients with hyperglycemia contributes to the normalization of the function of the damaged glomerular endothelium. With prolonged use leads to the reverse development of myocardial hypertrophy and pathological remodeling in the cardiovascular system, improves endothelial function and blood supply of the ischemic myocardium.

ACE inhibitors increase 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.

Pharmacokinetics:

Absorption from the gastrointestinal tract is 30%. Eating does not affect the absorption of the drug. Bioavailability averages 25-30%. Time to reach the maximum concentration in the blood plasma (T_max ) - 6-7 hours, in the early post-infarction period - 8-10 hours. The maximum concentration in the blood plasma (C_max) is 90 ng / ml. Lisinopril It is not lipophilic and practically does not bind to plasma proteins (less than 5%).Penetration through the blood-brain and placental barrier is weak. Lisinopril not biotransformed in the body. It is excreted by the kidneys unchanged. Half-life (T_1/2) is 12 hours. Cumulative properties do not. Accumulation in the body is observed only in severe renal failure (creatinine clearance less than 30 ml / min).

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

In patients with cirrhosis, the bioavailability of lisinopril (by 30%) and its clearance (by 50%) were reduced.

In patients with renal insufficiency (creatinine clearance less than 30 ml / min), the concentration of lisinopril is several times higher than the concentration in the blood plasma of healthy volunteers, the time to reach the maximum concentration in the blood plasma and the half-life have been increased.

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 drugs)

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

- Acute myocardial infarction (early (within the first 24 hours) treatment of patients with stable hemodynamic parameters, to maintain these parameters and prevention of left ventricular dysfunction and heart failure)

- Diabetic, nephropathy (to reduce albuminuria in patients with type 1 diabetes mellitus with normal BP and in patients with type 2 diabetes mellitus with arterial hypertension).

Contraindications:Hypersensitivity to lisinopril and / or other components of the drug, increased sensitivity to other ACE inhibitors, angioedema in history, including those associated with the use of ACE inhibitors, hereditary angioedema Quincke or idiopathic angioedema, age to 18 years (efficacy and safety not established), pregnancy, lactation.

Carefully:Stenosis of the aortic estuary, hypertrophic obstructive cardiomyopathy, arterial, hypotension, ischemic heart disease,coronary insufficiency; hyponatremia / diet with restriction of table salt, hyperkalemia; bilateral renal artery stenosis or stenosis of the single kidney with progressive azotemia, condition after kidney transplantation, marked renal failure (creatinine clearance less than 30 ml / min), hemodialysis using high-flow dialysis membranes (AN 69®); primary hyperaldosteronism; cerebrovascular diseases, incl. insufficiency of cerebral circulation; severe forms of diabetes mellitus; systemic diseases of connective tissue (including scleroderma, systemic lupus erythematosus); oppression of bone marrow hematopoiesis; hypovolemic conditions (including as a result of diarrhea, vomiting); Older age (over 65 years).

Pregnancy and lactation:

Data on the effect on the fetus in the first trimester of pregnancy is not present, in the II and III trimesters has an adverse effect on the fetus.

The use of lisinopril during pregnancy is contraindicated. When confirming the pregnancy, the drug should be stopped immediately.

Lizinopril penetrates the placenta and can lead to malformations of the fetus, incl. incompatible with life.

There is no data on the penetration of lisinopril into breast milk. However, if you need to treat the drug, breastfeeding should be discontinued.

For newborns and infants who have been exposed to ACE inhibitors, careful monitoring is recommended to timely detect a marked decrease in blood pressure, oliguria, and hyperkalemia.

Dosing and Administration:

Inside, regardless of food intake, once a day in the morning, preferably at the same time.

Dose selection is performed until the optimal (target level) is reached.

The maintenance dose is determined depending on the dynamics of blood pressure. Do not increase the dose of the drug earlier than in 2 weeks (accelerated dose titration is allowed in patients with asymptomatic left ventricular dysfunction, mild heart failure, arterial hypertension and hospitalized patients).

With arterial hypertension the initial dose is 10 mg / day, the maintenance dose is -20 mg / day, the maximum daily dose is 40 mg (increasing the dose above 40 mg / day usually does not lead to a further decrease in blood pressure). A full and stable effect develops within 2-4 weeks.

Prior therapy with diuretics should be canceled 2-3 days before the start of the use of lisinopril. If diuretics can not be canceled, the initial dose of lisinopril should not exceed 5 mg / day. In this case, after taking the first dose, medical supervision is recommended for several hours, taking into account the maximum hypotensive effect in 6-7 hours.

With Renovascular Hypertension or other conditions with increased activity of the renin-angiotensin-aldosterone system, the initial dose is 5 mg per day, under strict medical supervision in a hospital (blood pressure control, kidney function, potassium 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 excreted through the kidneys; the initial dose is determined depending on the creatinine clearance. Further, in accordance with the therapeutic effect and tolerability, a maintenance dose should be established in conditions of frequent monitoring of kidney function, potassium and sodium content in 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 indicated.

In chronic heart failure (concurrent with diuretics and / or cardiac glycosides) - lisinopril in a dose of 5 - 10 mg is used for maintenance therapy. The initial dose is 2.5 mg (2.5 mg or 5 mg tablets with a risk are used). The maximum daily dose is 20 mg.

Acute myocardial infarction (as part of combination therapy).

In the first day lisinopril is shown only to patients with stable hemodynamic parameters - 5 mg orally, then 5 mg after 1 day, 10 mg after two days and then 10 mg once a day. At the beginning of treatment or within the first 3 days after acute myocardial infarction, a lower dose of 2.5 mg / day is prescribed in patients with low systolic blood pressure (100-120 mm Hg).

The course of treatment - at least 6 weeks.

In the case of a decrease in blood pressure (systolic blood pressure is below or equal to 100 mm Hg), the daily dose of 5 mg should be temporarily reduced to 2.5 mg.

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 lisinopril should be discontinued.

With diabetic nephropathy 10 mg of lisinopril is applied once a day.The dose can be increased to 20 mg once a day if necessary in order to achieve diastolic blood pressure values below 75 mm Hg. in the "sitting" position for patients with type 2 diabetes and below 90 mm Hg. in the "sitting" position in patients with type 1 diabetes mellitus.

Side effects:

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - more than 10%; often - more than 1 and less than 10%; infrequently - more than 0,1 and less than 1%; rarely - more than 0.01 and less than 0.1%; very rarely, less than 0.01%, the frequency is unknown.

The most common (3 - 6%) occur side effects: dizziness, headache, dry cough, fatigue, nausea, diarrhea.

From the side of the cardiovascular system: often - marked decrease in blood pressure, orthostatic hypotension; infrequently - acute myocardial infarction or stroke, tachycardia, palpitations; Raynaud's syndrome; rarely - bradycardia, aggravation of the severity of symptoms and course of CHF, violation of atrioventricular conduction, chest pain.

From the central nervous system: often - dizziness, headache; infrequently - lability of mood,paresthesia, sleep disorders (drowsiness / insomnia), asthenia; rarely confusion, impaired vision; frequency unknown - depression, faint.

From the organs of hematopoiesis and lymphatic system: rarely - reduction of hemoglobin and hematocrit; - Very rarely - leukopenia, neutropenia, agranulocytosis, thrombocytopenia, hemolytic anemia, lymphadenopathy, oppression of bone marrow hematopoiesis, eosinophilia and leukocytosis.

From the respiratory system: often - cough; infrequently - rhinitis; very rarely - sinusitis, bronchospasm; allergic alveolitis / eosinophilic pneumonia.

From the digestive system: often - diarrhea, vomiting; infrequently - dyspepsia, changes in taste; abdominal pain; rarely dryness of the oral mucosa; very rarely - pancreatitis, jaundice, (hepatocellular or cholestatic), hepatitis, hepatic insufficiency, intestinal edema.

From the skin: infrequently - skin itching, rash, angioedema, swelling of the face, limbs, lips, tongue, larynx; rarely - hives, alopecia, psoriasis; very rarely - increased sweating, pemphigus, toxic epidermal necrolysis (Lyell's syndrome), erythema multiforme, Stevens-Johnson syndrome, vasculitis, exanthema; reaction photosensitivity.

From the urinary system: often - renal dysfunction; rarely - uremia, acute renal failure, very rarely - oliguria, anuria.

On the part of the reproductive system: infrequently - impotence; rarely - gynecomastia.

From the side of metabolism: very rarely - hypoglycemia.

From the endocrine system: rarely - the syndrome of impaired secretion of antidiuretic hormone.

Laboratory indicators: infrequently - increased urea concentration in the blood, hypercreatininaemia, hyperkalemia, increased activity of "liver" transaminases; rarely - hyperbilirubinemia, hyponatremia; very rarely - acceleration of the rate of erythrocyte sedimentation (ESR), positive results of the test for antinuclear antibodies.

Other: very rarely - fever, myalgia, myositis, arthralgia, arthritis, serositis, autoimmune diseases.

With the simultaneous administration of ACE inhibitors and intravenous sodium aurotomy malate, a symptom complex including facial flushing, nausea, vomiting and hypertension is described.

Overdose:

Symptoms: marked decrease in blood pressure, cough, dryness of the oral mucosa, dizziness, anxiety,increased irritability, drowsiness, vascular collapse, rapid breathing, palpitations, tachycardia, bradycardia, disturbance of water-electrolyte balance, renal failure, delayed urination.

Treatment: gastric lavage, adsorptive drugs, giving the patient a horizontal position with raised legs, intravenous injection of 0.9% sodium chloride solution, if necessary - vasopressor medicines, blood pressure control, water-electrolyte balance, creatinine. With persistent bradycardia - the use of an artificial pacemaker. Hemodialysis is effective.

Interaction:

Lizinopril can be used simultaneously with beta-blockers, acetylsalicylic acid, thrombolytic agents, nitrates.

With the simultaneous use of lisinopril with potassium-sparing diuretics (spironolactone, triamterone, amiloride, eplerenone), potassium preparations, potassium-containing substitutes for table salt, cyclosporine increases the risk of hyperkalemia, especially with impaired renal function. Joint use is allowed only with regular monitoring of potassium content in the blood serum and kidney function.

When using lisinopril with other antihypertensive drugs, including diuretics, beta-adrenoblockers, blockers of "slow" calcium channels, etc., an additive antihypertensive effect should be considered.

The combination of lisinopril with tricyclic antidepressants / antipsychotics can lead to a marked decrease in blood pressure.

Lizinopril slows the excretion of lithium preparations, so you should regularly monitor the concentration of lithium in the blood plasma.

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

Joint use of lisinopril with insulin and hypoglycemic agents for oral administration increases the risk of hypoglycemia, especially during the first month of therapy with an ACE inhibitor.

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2, acetylsalicylic acid in doses of more than 3 g / day (maximum daily dose), estrogens and adrenomimetics contribute to reducing the antihypertensive effect of lisinopril. With simultaneous use of NSAIDs and ACE inhibitors (or angiotensin II receptor antagonists) can lead to an increase in potassium in the blood and worsen kidney function.With simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate) describes a symptom complex, which includes facial flushing, nausea, vomiting and lowering blood pressure. The combined use of lisinopril with selective serotonin reuptake inhibitors can lead to severe hyponatraemia.

Co-administration with allopurinol, procainamide, cytostatics can lead to leukopenia.

Ethanol enhances the effect of the drug.

Special instructions:

Therapy with ACE inhibitors should be started under the control of blood pressure, taking into account the maximum effect of lisinopril after 6-8 hours (with myocardial infarction 8-10 h).

High-risk group development of dangerous adverse reactions are patients with. heart failure (with or without renal insufficiency). In such cases, treatment with lisinopril should be started under the strict supervision of a doctor in a hospital. Similar rules should also be adhered to when assigning patients with coronary heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.

A marked decrease in blood pressure after taking the first dose of the drug can develop, in particular, in patients with high plasma renin activity (for example, in the presence of diuretic therapy in high doses or congestive heart failure). The pronounced decrease in blood pressure arises with initially reduced volume of circulating blood due to diuretic therapy, diets with restriction of table salt, hemodialysis, diarrhea and vomiting. Before starting treatment with lisinopril, it is necessary to replenish the volume of circulating blood.

Transient arterial hypotension is not a contraindication for taking the next dose of the drug.

With the use of lisinopril in some patients with chronic heart failure with normal or low blood pressure, there may be a decrease in blood pressure, which is not a reason for stopping treatment.
With stenosis of the renal artery (especially with bilateral stenosis, or with stenosis of the single kidney artery), as well as inadequate circulation, due to lack of sodium and / or liquid, the use of lisinopril may lead to an increase in the concentration of urea and creatinine in the blood, impaired renal function, and acute renal failure.

Treatment with lisinopril with acute myocardial infarction spend on a background of standard therapy (thrombolytics, acetylsalicylic acid, beta-blockers). Compatible with intravenous nitroglycerin and transdermal therapeutic system (TTS) nitroglycerin.

Surgery / general anesthesia. With extensive surgical interventions, as well as with the use of other drugs that cause a decrease in blood pressure, lisinopril, blocking the formation of angiotensin II, can cause a pronounced unpredictable decrease in blood pressure. Before surgery, including dental surgery, you should inform the surgeon / anesthesiologist about the use of an ACE inhibitor.

In elderly patients the same dose leads to a higher concentration of the drug in the blood plasma, so special care is required when determining the dose. Angioedema when using ACE inhibitors, including lisinopril, can develop at any stage, treatment. When swelling of the tongue, throat, larynx, airway obstruction with lethal outcome may develop.

If these complaints appear, stop taking the medication immediately and consult a doctor.In such cases, a rapid subcutaneous injection of an adrenaline solution 0.1% (0.3-0.5 ml), the administration of glucocorticosteroids, antihistamines and / or measures to ensure airway patency.

ACE inhibitors often cause the development of angioedema in patients of the Negroid race, than in representatives of other races.

In patients with heart failure, diabetes mellitus, concurrently taking potassium supplements, potassium-containing salt substitutes, potassium-sparing diuretics, or other drugs that increase serum potassium levels (heparin), ACE inhibitors increase the risk of developing hyperkalemia.

Very rarely, with the use of ACE inhibitors, a syndrome that started with cholestatic jaundice or hepatitis was observed and progressed to fulminant necrosis in the liver and (sometimes) with a fatal outcome. The mechanism of development of this syndrome is unknown. When jaundice occurs on the background of the use of the drug or a pronounced, increased activity of "liver" transaminases, the drug should be discontinued and careful monitoring of the patient's condition.

The use of lisinopril as well as all ACE inhibitors may be accompanied by a dry cough that stops when the dose of the drug is lowered or treatment is stopped. Because the potential risk of agranulocytosis can not be ruled out, periodic monitoring of the blood picture is required.

In patients taking ACE inhibitors, during desensitization to the venom of Hymenoptera (bees and wasps), a life threatening anaphylactoid reaction may occur. It is necessary to temporarily stop treatment with an ACE inhibitor before starting the course of desensitization.

Anaphylactoid reactions may occur with simultaneous hemodialysis using high-flow membranes (including AN 69®), as well as during apheresis of low-density lipoproteins with adsorption to dextran sulfate.

It is necessary to consider the possibility of using a different type of membrane for dialysis or another antihypertensive drug.

Patients receiving hypoglycemic agents inside and insulin during the first month of therapy with ACE inhibitors should regularly monitor blood glucose.

Care should be taken when performing physical exercises,hot weather (the risk of dehydration and excessive blood pressure lowering due to a decrease in the volume of circulating blood).

During the period of treatment, it is not recommended to drink alcoholic beverages, since alcohol increases the antihypertensive effect of the drug.

Effect on the ability to drive transp. cf. and fur:It should be taken into account that there may be dizziness, so you should be careful.

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

Packaging:

For 10 or 15 tablets in a planar cell packaging made of polyvinylchloride film and aluminum foil printed lacquered.

For 2 or 3 contour packs of 10 tablets or 2 contour packs of 15 tablets together with instructions for use 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-000289

Date of registration:26.03.2010 / 30.03.2012

Expiration Date:Unlimited

The owner of the registration certificate:NIZHFARM, JSC NIZHFARM, JSC Russia

Manufacturer: & nbsp

SKOPINSKY FARM ZAVOD, ZAO Russia

Information update date: & nbsp25.02.2018

Illustrated instructions

Instructions

Lisinopril (Lisinopril)