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

Composition:In 1 tablet contains: active substance: lisinopril dihydrate (lisinopril) - 2.73 mg (2.50 mg); 5.46 mg (5.00 mg); 10.92 mg (10.00 mg); 21.84 mg (20.00 mg); Excipients: starch, pregelatinized (12,00 / 12,00 / 12,00 / 12,00 mg), corn starch (40,00 / 40,00 / 40,00 / 40,00 mg), calcium hydrophosphate (anhydrous) (93, 07 / 90.34 / 84.88 / 73.96 mg), mannitol (70.00 / 70.00 / 70.00 / 70.00 mg), magnesium stearate (2.20 / 2.20 / 2.20 / 2.20 mg).

Description:Tablets 2.5 mg: Biconvex tablets are oval in white.On one side is engraved "LSN 2,5".
Tablets 5 mg: Biconvex tablets are oval in white. On one side is the engraving "LSN 5", on the other - the dividing risk.
Tablets 10 mg: Biconvex tablets are oval in white. On one side is the engraving "LSN 10", on the other - the dividing risk.
Tablets of 20 mg: Biconvex tablets are oval in white. On one side is the engraving "LSN 20", on the other - the dividing risk.

Pharmacotherapeutic group:Angiotensin-converting enzyme inhibitor.

ATX: & nbsp

C.09.A.A.03 Lisinopril

C.09.A.A ACE Inhibitors

Pharmacodynamics:The angiotensin-converting enzyme (ACE) inhibitor reduces the formation of angiotensin II from angiotensin I. Reducing angiotensin II leads to a direct reduction in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the overall peripheral vascular resistance (OPSS), 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 the load in patients with chronic heart failure. Expands arteries more than veins.Some effects are explained by the effect on the renin-angiotensin-aldosterone system (RAAS). 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 (CHF), slow the progression of left ventricular dysfunction in patients who underwent acute myocardial infarction without clinical manifestations of heart failure. The beginning of the drug - after 1 hour, the maximum antihypertensive effect is achieved after 6-7 hours and persists for 24 hours. The duration of the effect also depends on the amount of the dose taken. With arterial hypertension, the effect is observed in the first days after the start of treatment, stable action develops after 1-2 months. therapy. With a sharp reversal of lisinopril, there was no pronounced increase in blood pressure.
Lizinopril reduces albuminuria. Does not affect the concentration of glucose in the blood in patients with diabetes 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 29%. The maximum concentration in the blood plasma (C_max) is achieved after 7 hours. Food intake does not affect the absorption of lisinopril.
Distribution. Lisinopril slightly binds to blood plasma proteins. 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. Half-life (T_1/2) is 12.6 hours. The clearance of lisinopril is 50 ml / min. The decrease in serum concentration of lisinopril occurs in two phases. The bulk of lisinopril is excreted during the initial alpha phase (effective T_1/2 - 12 hours), followed by a terminal distant beta phase (about 30h).
Pharmacokinetics in selected patient groups
In patients with CHF, absorption and clearance of lisinopril are reduced, bioavailability is 16%.
In patients with renal insufficiency (creatinine clearance less than 30 ml / min), the concentration of lisinopril is several times higher than the plasma concentration in healthy volunteers, with an increase in the time to reach C_max in blood plasma and an increase T_1/2.
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.
In patients with liver cirrhosis, the bioavailability of lisinopril is reduced by 30%, and the clearance by 50% compared to patients with normal liver function.
In elderly patients, the concentration of lisinopril in the blood is increased by an average of 60%.

Indications:- Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs).
Chronic heart failure (as part of combination therapy).
- Early treatment of acute myocardial infarction (within the first 24 hours with stable hemodynamic parameters to maintain these parameters and prevention of left ventricular dysfunction and heart failure).
- Diabetic nephropathy (decrease in albuminuria in patients with type 1 diabetes mellitus at normal arterial pressure, and in patients with type 2 diabetes mellitus with hypertension).

Contraindications:Hypersensitivity to lisinopril, other components of the drug, or other ACE inhibitors; angioedema in the anamnesis (incl.and from the use of other ACE inhibitors); hereditary angioedema and / or idiopathic angioedema; age under 18 years (effectiveness and safety not established); pregnancy and the period of breastfeeding; simultaneous use with aliskirnym and aliskirensoderzhaschimi drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate (GFR) <60 ml / min / 1.73 m²).

Carefully:Two-sided stenosis of the renal arteries or stenosis of the artery of a single kidney with progressive azotemia; condition after kidney transplantation; kidney failure; hemodialysis using high-flow dialysis membranes (AN69®); azotemia; hyperkalemia; stenosis of the aortic aorta; hypertrophic obstructive cardiomyopathy; primary hyperaldosteronism; arterial hypotension; cerebrovascular diseases (including cerebral circulatory insufficiency); ischemic heart disease (IHD); coronary insufficiency; autoimmune diseases of connective tissue (including scleroderma, systemic lupus erythematosus); oppression of bone marrow hematopoiesis; state,accompanied by a decrease in the volume of circulating blood (BCC) (including as a result of diarrhea, vomiting); use in patients on a diet with restriction of table salt; in elderly patients; simultaneous use with potassium preparations, diuretics, other antihypertensive drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), lithium preparations, antacids, colestyramine, ethanol, insulin, other hypoglycemic drugs, allopurinol, procainamide, gold preparations, antipsychotics, tricyclic antidepressants, barbiturates, beta- adrenoblockers, blockers of slow calcium channels.

Pregnancy and lactation:The use of the drug Lizinopril-Teva during pregnancy is contraindicated. When diagnosing 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 effect of the drug on the fetus in case of application in the I trimester is 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. There is no data on the penetration of lisinopril into breast milk. If you need to use the drug Lizinopril-Teva during lactation, breastfeeding should be discontinued.

Dosing and Administration:The drug Lizinopril-Teva is taken orally 1 time per day, regardless of the time of ingestion, preferably at the same time of day. The dose is selected individually.
When arterial hypertension patients who do not receive other antihypertensives are given 5 mg per day. In the absence of therapeutic effect, the dose is increased every 2-3 days by 5 mg to a 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 average daily maintenance dose of 20 mg. The maximum daily dose is 40 mg. The therapeutic effect usually develops in 2-4 weeks from the start of treatment, which should be taken into account when increasing the dose. With insufficient effect, simultaneous application of the drug with other antihypertensive drugs is possible.
If the patient received a preliminary treatment with diuretics, then the medication should be stopped 2-3 days before the Lizinopril-Teva drug is used. If this is not possible, the initial dose of Lysinopril-Teva 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.
In the case of renovascular hypertension associated with increased activity of RAAS, it is also advisable to use a low initial dose of 2.5 mg per day in dynamics, under enhanced medical supervision (control of blood pressure, kidney function, potassium content in blood serum). The maintenance dose, continuing strict medical control, should be determined depending on the dynamics of blood pressure.
When chronic heart failure the initial dose of 2.5 mg per day, the dose is gradually increased (no more than 10 mg, with an interval of not less than 2 weeks), depending on blood pressure. The maximum daily dose is 20 mg.
When early treatment of acute myocardial infarction myocardium in the first day of the dose is 5 mg, then 5 mg every other day, 10 mg after two days and then 10 mg per day as maintenance therapy.In patients with acute myocardial infarction, the drug should be used for at least 6 weeks. At the beginning of treatment or within the first 3 days after myocardial infarction in patients with low systolic blood pressure (120 mm Hg or lower), a smaller dose of Lysinopril-Teva 2.5 mg is used. If the systolic blood pressure is less than or equal to 100 mm Hg. Lizinopril-Teva is not recommended. With concomitant renal failure (CC less than 80 ml / min.), Appropriate dose adjustment should be made.
When diabetic nephropathy In patients with type 1 diabetes mellitus, the drug Lizinopril-Teva is used at a dose of 10 mg per day. If necessary, the dose can be increased to 20 mg per day in order to achieve a diastolic blood pressure below 75 mm Hg. Art. in the "sitting" position. Patients with type 2 diabetes mellitus Lizinopril-Teva are used in the same dose, in order to achieve diastolic blood pressure below 90 mmHg. in the "sitting" position.
When renal failure and in patients on hemodialysis, the initial dose is set depending on the QA. The maintenance dose is determined depending on blood pressure (under the control of kidney function, the content of potassium and sodium in the blood).

CK (ml / min.)	Initial dose (mg / day)
30-80	5-10
10-29	2,5-5
less than 10 (including patients on hemodialysis)	2,5

Side effects:The most common side effects: dizziness, headache, fatigue, diarrhea, dry cough, nausea.
The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%.
From the cardiovascular system: often - marked decrease in blood pressure, orthostatic hypotension; infrequently - acute myocardial infarction, tachycardia, palpitation; Raynaud's syndrome; rarely - bradycardia, tachycardia, aggravation of symptoms of CHF, violation of atrioventricular conduction, chest pain.
From the central nervous system: often - dizziness, headache; infrequently - lability of mood, paresthesia, sleep disturbance, stroke; rarely - confusion, asthenic syndrome, convulsive twitching of the muscles of the limbs and lips, drowsiness.
From the hemopoietic system and lymphatic system: rarely - reduction of hemoglobin, hematocrit; very rarely - leukopenia, neutropenia, agranulocytosis, thrombocytopenia, eosinophilia, erythropenia, hemolytic anemia, lymphadenopathy, autoimmune diseases, oppression of bone marrow function.
From the respiratory system: often - cough, infrequently - rhinitis, very rarely - sinusitis, bronchospasm, allergic alveolitis / eosinophilic pneumonia, dyspnea.
From the digestive system: often - diarrhea, vomiting; infrequently - indigestion, changes in taste, abdominal pain; rarely dryness of the oral mucosa; very rarely - pancreatitis, jaundice (hepatocellular or cholestatic), hepatitis, hepatic insufficiency, intestinal edema, anorexia.
From the skin: infrequently - itchy skin, rash; rarely - angioedema, swelling of the face, limbs, lips, tongue, larynx, urticaria, alopecia, psoriasis; rarely -
increased sweating, vasculitis, pemphigus, photosensitivity, toxic epidermal necrolysis (Lyell's syndrome), erythema multiforme, Stevens-Johnson syndrome.
From the urinary system: often - renal dysfunction; infrequently, uremia, acute renal insufficiency; very rarely - anuria, oliguria, proteinuria.
On the part of the reproductive system: infrequently - impotence, rarely - gynecomastia.
From the side of metabolism: very rarely - hypoglycemia.
From the laboratory indicators: infrequent increase of urea concentration in the blood, hypercreatininaemia, hyperkalemia, increased activity of "hepatic" transaminases, rarely - hyperbilirubinemia, hyponatremia, increased erythrocyte sedimentation rate, false positive results of antinuclear antibodies test.
From the musculoskeletal system: rarely - arthralgia / arthritis, myalgia.
Other: rarely - with the simultaneous use of gold medications intravenously, the symptom complex is described, which includes facial hyperemia, nausea, vomiting and a decrease in blood pressure (see section "Interaction with other medicinal products").

Overdose:Symptoms: a pronounced decrease in blood pressure, dryness of the oral mucosa, a violation of the water-electrolyte balance, renal failure, rapid breathing, tachycardia, palpitations, bradycardia, dizziness, anxiety, irritability, cough, drowsiness, urinary retention, constipation, collapse, hyperventilation of the lungs .
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 bradycardia, which is resistant to treatment, it is necessary to use an artificial "driver" of the rhythm. It is necessary to monitor blood pressure, indicators of water-electrolyte balance. Hemodialysis is effective.

Interaction:Caution should be applied lisinopril simultaneously with potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium preparations, salt substitutes, containing potassium, cyclosporine - increases the risk of hyperkalemia, especially with impaired renal function. Therefore, these combinations should be used only on the basis of the individual solutions at regular physician monitoring the potassium content in blood serum and renal function. With simultaneous use with diuretics and other antihypertensive drugs, the antihypertensive effect of lisinopril is enhanced.
When applied simultaneously with NSAIDs (including selective inhibitors of cyclooxygenase-2 (COX-2)), acetylsalicylic acid at a dose of more than 3 g / day, estrogens, and sympathomimetics, the antihypertensive effect of lisinopril decreases.NSAIDs, including COX-2, and ACE inhibitors increase serum potassium levels and can worsen renal function. This effect is usually reversible.
Lizinopril slows down the excretion of lithium preparations, therefore, with simultaneous application, a reversible increase in its concentration in the blood plasma occurs, which can increase the likelihood of unwanted phenomena, therefore, the concentration of lithium in serum should be monitored regularly.
With simultaneous use with antacids and colestyramin, suction of lisinopril from the digestive tract decreases.
Ethanol enhances the action of lisinopril. With simultaneous use with insulin and hypoglycemic agents for oral administration, the risk of developing hypoglycemia increases.
With the simultaneous use of lisinopril with vasodilators, barbiturates, antipsychotic agents (antipsychotics), tricyclic antidepressants, blockers of "slow" calcium channels, beta-adrenoblockers, an increase in the antihypertensive effect is possible.
With the simultaneous use of ACE inhibitors and intravenous drugs of gold (sodium arothiamalate), a simp-tomocomplex is described, including facial hyperemia, nausea, vomiting and a decrease in blood pressure.Joint application with allopurinol, procainamide, cytostatics can lead to leukopenia. Double blockade of RAAS with the use of angiotensin II receptor antagonists (APA II), ACE inhibitors or aliskiren (renin inhibitor) is associated with an increased risk of arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy. Regular monitoring of blood pressure, kidney function and electrolyte content in the blood are necessary.

Special instructions:Most often, a marked decrease in blood pressure occurs with a decrease in bcc caused by diuretic therapy, a decrease in table salt content in food, dialysis, diarrhea, or vomiting. Under the supervision of a doctor, it is recommended to use the drug Lizinopril-Teva in patients with IHD, cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke. The use of lisinopril-Teva can lead to impaired renal function, acute renal failure, which is usually reversible after drug withdrawal.
Transient arterial hypotension is not a contraindication for the further use of the drug.
In the case of stenosis of the renal artery (especially with bilateral stenosis or in the presence of stenosis of the artery of a single kidney), as well as peripheral circulatory insufficiency resulting from hyponatremia and hypovolemia, the use of the drug Lizinopril-Teva can lead to impaired renal function, acute renal failure, which usually turns out to be reversible after drug discontinuation.
The drug Lizinopril-Teva can be used simultaneously with standard therapy of acute myocardial infarction (thrombolytics, acetylsalicylic acid as an apyaggregant agent, beta-adrenoblockers).
The drug Lizinopril-Teva can be used concurrently with intravenous nitroglycerin or with the use of therapeutic transdermal systems of nitroglycerin.
Lizinopril-Teva is not recommended in patients who underwent acute myocardial infarction if systolic blood pressure does not exceed 100 mm Hg.
In surgical interventions, as well as in 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), the surgeon / anesthesiologist should be informed of the use of an ACE inhibitor.
In elderly patients, the use of standard doses leads to a higher concentration of the drug in the blood, therefore special care is required in determining the dose, although there is no difference in the antihypertensive action of Lysinopril-Teva in elderly and young patients.
Since the potential risk of agranulocytosis can not be ruled out, periodic monitoring of peripheral blood is required.
Angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx that may occur at any time of treatment has rarely been seen in patients taking an ACE inhibitor, including lisinopril. In this case, treatment with the drug should be stopped as soon as possible, and the patient should be monitored until the symptoms regress completely. Angioedema with edema of the larynx can be lethal. Swelling of the tongue, epiglottis or larynx may be the cause of airway obstruction,therefore it is necessary to immediately carry out appropriate therapy (0.3-0.5 ml of 1: 1000 epinephrine (adrenaline) solution subcutaneously) and / or measures to ensure airway patency. In cases where the edema is localized only on the face and lips, the condition usually passes without treatment, but antihistamines can be used. ACE inhibitors often cause the development of angioedema in patients of the Negroid race, than in representatives of other races.
The risk of developing angioedema is increased in patients who have a history of angioedema, not associated with previous treatment with ACE inhibitors. In patients taking ACE inhibitors during the desensitization procedure for venom of Hymenoptera, extremely rare, life-threatening anaphylactoid reactions can develop. This can be avoided if the treatment with an ACE inhibitor is temporarily discontinued before each desensitization procedure on the hymenoptera.
Anaphylactoid reactions are also observed in patients on hemodialysis using high-flow dialysis membranes (AN69®), which simultaneously take ACE inhibitors.In such cases, one should consider the possibility of using another type of membrane for dialysis or another antihypertensive drug.
In patients receiving hypoglycemic drugs for oral administration and insulin. During the first month of therapy with ACE inhibitors, blood glucose should be monitored regularly.
Very rarely, with the use of ACE inhibitors, a syndrome that started with cholestatic jaundice and progressed to fulminant liver necrosis, sometimes with a fatal outcome, was observed. The mechanism of development of this syndrome is unknown. When jaundice appears on the background of the use of the drug Lizinopril-Teva or a marked increase in the activity of "liver" transaminases, the drug is canceled and the patient's condition is monitored.
Cough was used in the use of ACE inhibitors. Cough is dry, prolonged,
which disappears after discontinuation of treatment with an ACE inhibitor. With a differential diagnosis of cough, one should also consider a cough caused by the use of an ACE inhibitor.
Simultaneous use of ACE inhibitors, ARA II or aliskiren increases the risk of hypotension, gipsrkalismia and renal dysfunction (including acute renal failure).Double blockade of RAAS with the use of ACE inhibitors, ARA II or aliskiren is not recommended.
If a double blockade of RAAS is considered absolutely necessary, the treatment should only take place under the supervision of specialists and should be accompanied by careful and frequent monitoring of kidney function, electrolyte content and blood pressure. ACE inhibitors and ARA II, should not be used simultaneously in patients with diabetic nephropathy.

Effect on the ability to drive transp. cf. and fur:Caution should be used when taking Lizinopril-Teva because it is possible to develop arterial hypotension, dizziness and drowsiness, which can affect the ability to drive vehicles and work with potentially dangerous mechanisms.

Form release / dosage:Tablets 2.5 mg; 5 mg; 10 mg; 20 mg.

Packaging:Tablets 2.5 mg: 10 tablets in a blister of Al / PVC / PVDC.
3 blisters together with instructions for use in a pack of cardboard.
Tablets 5 mg: 10 tablets in a blister of Al / PVC / PVDC.
1 or 3 blisters together with instructions for use in a cardboard pack.
Tablets 10 mg: 10 tablets in a blister of Al / PVC / PVDC.
1,2 or 3 blisters together with instructions for use in a pack of cardboard.
Tablets of 20 mg: 10 tablets in a blister of Al / PVC / PVDC.
1,2 or 3 blisters together with instructions for use in a pack of cardboard.
When produced at OOO Teva, Russia
Tablets 5 mg; 10 mg; 20 mg:
10 tablets in a blister of PVC / PVDC film according to GOST 25250-88 or the European Pharmacopoeia of the current edition and aluminum foil according to GOST 745-2014 or TU 9570-001-63543701-11. Tablets 5 mg:
1 or 3 blisters together with instructions for use in a pack of cardboard in accordance with GOST 12303-80 from cardboard type chrome or chrome-ersatz according to GOST 7933-89 or other similar quality. Tablets 10 mg and 20 mg:
1,2 or 3 blisters together with instructions for use in a cardboard pack in accordance with GOST 12303-80 from cardboard type chrome or chrome-ersatz according to GOST 7933-89 or other similar quality.

Storage conditions:Store at a temperature not exceeding 25 ° C. Keep out of the reach of children!

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000973

Date of registration:18.10.2011 / 22.06.2016

Expiration Date:18.10.2016

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Works Private, Ltd. Co. Hungary

Representation: & nbspTeva Teva Israel

Information update date: & nbsp2016-11-16

Illustrated instructions

Instructions

Lizinopril-Teva (Lisinopril-Teva)