Lizinopril-Lupine 5 mg tablet number 30
Author Ольга Кияница
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Lisinopril (LISINOPRIL) user manual
active ingredient: lisinopril; 1 tablet contains lisinopril dihydrate equivalent to lisinopril 5 mg or 10 mg or 20 mg
auxiliary substances: mannitol (E 421), calcium phosphate, corn starch, corn starch, silicon dioxide colloid, magnesium stearate, iron oxide red (E172).
Basic physical and chemical properties:
tablets of 5 mg round, biconvex without a pink coat, embossed "5" on one side and a fault line on the other;
tablets of 10 mg round, biconvex without a pink coat, embossed "10" on one side and a fault line on the other;
tablets of 20 mg round, biconvex without a shell of pink color, embossed "20" on one side and a line of a fault on the other.
ACE inhibitors (ACE). The ATX code is C09A A03.
Lizinopril reduces the level of angiotensin II and aldosterone in the plasma, while increasing the concentration of the bradykinin vasodilator. Lizinopril causes a decrease in peripheral vascular resistance and arterial pressure, the minute volume of the heart can increase with unchanged heart rate, and kidney blood flow may also increase.
The arterial pressure begins to decrease one hour after ingestion, the maximum hypotensive effect is achieved after 6 hours. The duration of action of lisinopril (about 24 hours) depends on the dose. With long-term treatment, the effectiveness of the drug is not reduced. With a sharp cessation of treatment, large changes in blood pressure (withdrawal syndrome) does not occur.
Although the primary action of lisinopril is associated with the renin-angiotensin-aldosterone system, the drug is also effective in hypertension, which occurs with a low content of renin.
In addition to directly lowering arterial pressure, lisinopril reduces albuminuria due to changes in the histology and hemodynamics of the glomerular renal apparatus. In the course of controlled trials, no changes in blood sugar level or an increase in hypoglycemia were observed in patients with diabetes mellitus.
It plays a positive role in restoring the function of damaged endothelium in patients with hyperglycemia.
With oral intake of lisinopril, the maximum concentration in the blood plasma is reached at about 7:00. Judging by the amount excreted in the urine, the average rate of absorption of lisinopril is approximately 25% when taking a dose of 5-80 mg. The variability of indicators between patients can be from 6 to 60%. The bioavailability of lisinopril decreases to about 16% in patients with NYHA class II-IV heart failure. Eating does not affect the absorption of lisinopril.
In addition to binding with ACE, lisinopril does not bind to other blood plasma proteins. As studies on animals show, lisinopril in a small amount penetrates the blood-brain barrier.
Lizinopril is not metabolized and is excreted exclusively by the kidneys in unchanged form. After increasing the dose, the effective half-life is 12.6 hours. The clearance of lisinopril is approximately 50 ml / min in healthy volunteers. After the withdrawal of a significant amount of the free active, the slower removal of the fraction associated with the ACE follows.
Impaired liver function
In patients with cirrhosis of the liver, suction of lisinopril is slowed by approximately 30% (as determined in urinary excretion) depending on the liver function disorder. On the other hand, its withdrawal decreases and leads to an increase in the effectiveness of lisinopril by 50%.
Impaired renal function
Violation of kidney function reduces the excretion of lisinopril, which is excreted by the kidneys. This decrease is of clinical importance only when the level of glomerular filtration is less than 30 ml / min. If the creatinine clearance is 30-80 ml / min, the average area under the curve increases only by 13%. If the creatinine clearance is from 5 to 30 ml / min, despite this, the average area under the curve increases 4.5 times compared with the norm. Lizinopril can be removed by dialysis.
In the presence of heart failure, the effect of lisinopril increases (AUC increases by about 25%). On the other hand, the bioavailability of lisinopril is reduced to about 16% in patients with heart failure.
In elderly patients, the level of lisinopril is usually higher due to a violation of the kidney function AUC approximately 60% higher than in younger patients.
Heart failure (symptomatic treatment).
Acute myocardial infarction (short-term treatment (6 weeks) of hemodynamically stable patients no later than 24 hours after acute myocardial infarction).
Treatment of initial nephropathy in patients with type II diabetes, arterial hypertension.
Hypersensitivity to the active or auxiliary substances of the drug.
Angioedema in history, associated with previous treatment with other ACE inhibitors.
Hereditary or idiopathic angioedema.
Stenosis of the aorta or mitral valve or hypertrophic cardiomyopathy with a violation of hemodynamics.
Stenosis of the renal artery (bilateral or unilateral).
A condition with unstable hemodynamics after acute myocardial infarction.
Use for patients on hemodialysis using high-flow membranes (eg AN 69).
The level of creatinine in the serum is> 220 μmol / l.
Pregnant women or women who plan to become pregnant.
Interaction with other drugs and other interactions
Potassium-sparing diuretics and potassium supplements
Simultaneous use of potassium-sparing diuretics (eg spironolactone, triamterene and amiloride), potassium and potassium-containing salt substitutes requires caution. Hyperkalemia in some cases can lead to impaired renal function.For this reason, this combination of drugs can be prescribed only with further careful monitoring of the doctor and with regular monitoring of the potassium level in the serum and kidney function.
Simultaneous reception of diuretics with lisinopril, as a rule, has an antihypertensive effect. Special care should be exercised with the addition of lisinopril in the therapy of patients taking diuretics, since a significant reduction in blood pressure is possible due to a decrease in the volume of the intercellular fluid and / or excessive removal of sodium chloride from the body. In view of the foregoing, the risk of developing symptomatic hypotension can be reduced by stopping diuretics and increasing fluid intake or salt intake before starting the dosage of lisinopril, and also at the start of treatment with low doses of ACE inhibitors.
Other antihypertensive agents
Taking other concomitant antihypertensive drugs can enhance the antihypertensive effect of lisinopril.
Simultaneous intake of nitroglycerin and other nitrates or other vasodilators can further reduce blood pressure.
Non-steroidal anti-inflammatory drugs (including acetylsalicylic acid in a dose of 3 g / day)
Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of ACE inhibitors. In addition, an increase in serum potassium levels caused by NSAIDs and ACE inhibitors is reported, which can lead to impaired renal function. This action, as a rule, is reversible, and its manifestation is possible, first of all, in patients with a previous renal dysfunction.
Acetylsalicylic acid, thrombolytic drugs, beta-blockers, nitrates
Lizinopril can be used concomitantly with acetylsalicylic acid (in cardiac doses), thrombolytic drugs, beta-blockers and / or nitrates under the supervision of a lactar.
ACE inhibitors can reduce the excretion of lithium, may be accompanied by an increase in toxicity. Taking into account this fact, simultaneous use of lisinopril with lithium preparations is not recommended, but if simultaneous reception of these drugs is necessary, the level of lithium in the blood plasma should be regularly monitored.
Simultaneous reception of antidiabetic agents with ACE inhibitors can enhance the hypoglycemic effect of insulin and sulfonylureas, which increases the risk of symptomatic hypoglycemia. However, an increase in glucose tolerance may reduce the necessary dose of insulin or sulfonylurea. This interaction, as a rule, manifests itself in the first week of combined treatment in patients with renal insufficiency.
Sympathomimetics can reduce the hypotensive effect of ACE inhibitors. For this reason, the patient's blood pressure should be monitored more closely to determine if the desired therapeutic effect has been achieved.
Tricyclic antidepressants, antipsychotics, anesthetics
Simultaneous reception of tricyclic antidepressants, neuroleptics or anesthetics may increase the hypotensive effect of lisinopril.
Nitrite reactions (symptoms of vasodilation, including hyperemia, nausea, dizziness and arterial hypotension, which can occur in severe form) as a result of gold injections (for example sodium once) are more frequent in patients who simultaneously take lisinopril.
A significant reduction in blood pressure accompanied by symptomatic hypotension may occur in patients with hypovolemia and / or a decrease in the volume of intercellular fluid resulting from the treatment with diuretics or in the case of restriction of consumption of edible salt and other forms of fluid loss (increased sweating, prolonged vomiting, diarrhea , dialysis), as well as in case of heart failure. In the event of arterial hypotension, the patient should be placed in a horizontal position, as an obligatory measure, intravenous fluid infusion is recommended (infusion of physiological solution). Transient arterial hypotension, as a rule, is not a contraindication for further treatment, but it may be necessary to temporarily stop therapy or reduce the dose.
If possible, hypovolemia should be eliminated and / or the volume of intercellular fluid decreased before treatment with lisinopril and carefully monitor the effect of the initial dose on blood pressure. In the case of cerebral circulation or ischemic heart disease, a sharp initial drop in blood pressure may be the cause of stroke or myocardial infarction.
In the case of acute myocardial infarction, it is forbidden to use lisinopril if the treatment with vasodilating drugs can worsen the hemodynamic status of the patient (for example, if the systolic blood pressure is 100 mm Hg. Or below) or in case of cardiogenic shock. If the systolic blood pressure is 120 mm Hg. Art. or lower, low doses (2.5 mg / day) should be administered within the first 3 days after the infarction. With arterial hypotension, maintenance doses should be reduced to 5 mg or temporarily to 2.5 mg. With persistent arterial hypotension (systolic blood pressure below 90 mm Hg St for more than 1:00), discontinue treatment with this medication.
Aortic stenosis / hypertrophic cardiomyopathy
Like all vasodilators, ACE inhibitors should be used with caution, given the previous obstruction of outflow tracts.
Impaired renal function
In case of impaired renal function (creatinine clearance <80 ml / min), the initial dose of lisinopril should be selected depending on the creatinine clearance (see the section "Method of administration and dose") and the clinical response to treatment. For such patients, continuous monitoring of the potassium and creatinine concentrations in the blood is recommended.
In patients with heart failure, arterial hypotension, which occurs after the initiation of therapy with ACE inhibitors, can lead to impaired renal function. There was reported acute renal failure, which in such cases, as a rule, is reversible.
In the case of stenosis of the renal artery (in particular in the case of bilateral stenosis or stenosis of the artery of a single kidney), as with hypovolemia and / or a decrease in the volume of intercellular fluid or insufficient circulation, arterial hypotension, developed with the use of lisinopril, may cause or enhance renal dysfunction, which can lead to the development of acute renal failure, the latter is usually reversible after discontinuation of therapy. A slight or short-term increase in AMC and creatinine levels may also not be associated with vascular kidney disease, including in the case of simultaneous intake of diuretics. It is necessary to exercise special care and carry out constant monitoring of renal function in patients with severe renal dysfunction (creatinine clearance <30 ml / min).
Do not initiate treatment if an acute myocardial infarction develops, if the kidney function of the patient is at risk (serum creatinine levels above 177 μmol / L and / or albuminuria above 500 mg / 24 hours). In conditions of renal impairment developed in the treatment (serum creatinine level is above 265 μmol / l or twice as high as the baseline level), the doctor should consider the possibility of cessation of treatment.
Rarely reported angioedema of the face, extremities, lips, tongue, pharynx and / or larynx in patients undergoing ACE inhibitors, including lisinopril. Edema can develop during treatment in 0.1-1% of patients. In this case, the treatment should be stopped immediately, the patient should be monitored until the symptoms disappear completely.
Even with complete rapid disappearance of the edema from the face and lips, antihistamines can be used to relieve symptoms. Angioedema, affects the larynx, can lead to death. The defeat of the tongue, vocal cuff, or throat may cause airway obstruction, therefore, the appropriate treatment should immediately begin: 0.3-0.5 ml of a solution of epinephrine 0.1% (0.3-0.5 mg epinephrine) subcutaneously or 0, 1 ml intravenously slowly, the use of glucocorticoids, antihistamines.
Surgery / anesthesia
During a cavitary operation or general anesthesia with the use of drugs provoking the development of arterial hypotension, lisinopril blocks the formation of angiotensin II against the background of compensatory renin release.Arterial hypotension, which develops as a result of this mechanism, can be eliminated by replenishing the volume of the fluid.
Anaphylactoid reactions have been reported in patients undergoing dialysis using high-flux polyacrylonitrile membranes (eg, AN 69) and concomitantly taking an ACE inhibitor. This combination should be avoided, and attention should be paid to the use of another type of dialysis membrane or other class of antihypertensive agents.
Ateresis of LDL
Anaphylactoid reactions that pose a threat to life (eg, deep hypotension, respiratory distress, vomiting, allergic skin reactions) may develop in patients undergoing ACE inhibitors during LDL (low density lipoprotein) - apheresis with dextran sulfate. For this reason, during apheresis of LDL, ACE inhibitors used to treat hypertension or heart failure should be temporarily replaced with other drugs.
Desensitization caused by insect venom refers to anaphylactoid reactions in some patients taking ACE inhibitors. These reactions, which create a life threat, can be avoided by early withdrawal from the use of ACE inhibitors.
Neutropenia / agranulocytosis
Neutropenia / agranulocytosis, thrombocytopenia and anemia can develop during treatment with ACE inhibitors in patients with hypertension. These pathologies were rarely observed in patients with normal renal function and in the absence of other complications. Neutropenia and agranulocytosis disappeared after discontinuation of treatment with ACE inhibitors. Lizinopril should be used with caution in patients with impaired renal function, particularly in diseases affecting the vascular system of both kidneys and connective tissue (eg, in systemic lupus erythematosus or scleroderma), and with concomitant immunosuppressive therapy (eg, corticosteroids, cytotoxic agents, antimetabolites).The use of ACE inhibitors in these patients may be accompanied by the development of a particularly acute infections, in some cases do not respond to intensive antibiotic treatment.
These patients should be periodically check the level of leukocytes in the blood for the treatment with lisinopril and the patient should be warned of the need to report the occurrence of any infections.
Ethnic features (race)
ACE inhibitors are the cause of angioedema is more common in blacks patients than in Caucasians.
As is the case with other ACE inhibitor, lisinopril efficiency is increased in patients blacks, among them due to the presence of large amounts of low-renin hypertension patients as compared to Caucasians.
Very rarely, ACE inhibitors can accelerate the development of cholestatic jaundice or hepatitis, can lead to the rapid development of necrosis and sometimes death. The root cause of this process is unknown. If patients taking lisinopril, develop jaundice or marked elevation of liver enzymes should discontinue the use of lisinopril and continue treatment with alternative drugs.
Treatment with lisinopril may be accompanied by the development of hyperkalemia, especially in patients with renal insufficiency and / or heart failure. Potassium supplement or treatment with potassium-sparing diuretics are generally not recommended as it may lead to a significant increase in serum potassium levels. If simultaneous reception of the aforementioned drugs is required, it is recommended frequent monitoring of serum potassium levels.
In elderly patients the same dose may be accompanied by an increase in its concentration in the blood, for this reason, the dose should be determined with caution and taking into account the state of the patient's renal function. Despite this, between young and elderly patients showed no significant difference in the effectiveness of antihypertensive lisinopril.
It reported the occurrence of cough during treatment with ACE inhibitors. The cough is usually dry, no sputum, stopped after stopping treatment.
A more careful monitoring of the glucose level in the first month of treatment with ACE inhibitors in addition to the previous treatment with insulin or oral hypoglycemic agents.
of lithium drugs
It is not recommended to combine drugs lithium and lisinopril.
Use during pregnancy or lactation.
The gestation period. Lisinopril Lupine contraindicated use for pregnant women or women trying to conceive. If during treatment confirmed the pregnancy, its use must be stopped immediately and, if necessary - to replace another drug approved for use for pregnant women.
The period of breastfeeding. Since the information about the possibility of the use of lisinopril during breast-feeding is not, the drug Lisinopril Lupine contraindicated.
Ability to influence the reaction rate when driving or operating other machinery.
Given the possibility of dizziness and fatigue development, lisinopril may affect the ability of car driving and operating machinery, especially at the beginning of treatment.
Therefore it is necessary to refrain from control and road works with the mechanisms to establish individual response to the drug.
Dosing and Administration
Take 1 times a day at the same time, regardless of the meal.
The initial dose.The recommended starting dose is usually 10 mg. In patients with very active renin-angiotensin-aldosterone system (especially with renovascular hypertension, excessive excretion of sodium chloride and / or dehydration, cardiac decompensation or severe hypertension) probably excessive fall in blood pressure after the first dose. Therefore, at the beginning of the treatment, such patients should be under the supervision of a physician recommended starting dose is 2.5 mg * 5. Patients with renal failure also necessary to reduce the initial dose (see. Table 1).
Supportive dose.Typically, an effective maintenance dose is 20 mg 1 time per day. If when applying the prescribed dose for 2-4 weeks is not achieved the desired therapeutic effect, the dose can be further increased. The maximum daily dose should not exceed 80 mg.
If patients take diuretic 2-3 days before beginning therapy with lisinopril receiving these agents should be discontinued. If this is not possible, the initial dose of lisinopril should not exceed 5 mg per day, it is recommended to provide medical monitoring of patients after the first dose, as may develop symptomatic hypotension (maximum effect seen after 6 h after drug administration).
At the start of treatment with lisinopril may develop hypotension. This is most likely in patients already diuretics. Because these patients may experience a dehydration and / or excessive excretion of sodium chloride, the drug should be used with caution.
Lisinopril can be used simultaneously with diuretics and / or digitalis drugs. In this case, in advance, if possible, the diuretic dose should be reduced. Starting lisinopril daily dose of 2.5 mg * may be gradually increased to a maintenance dose of 5-20 mg per day.
The recommended dose rate of increase after 2 weeks is not more than 10 mg.
The maximum daily dose of lisinopril - 35 mg / day.
Before treatment lisinopril and during treatment should regularly monitor blood pressure, renal function, potassium and sodium concentration in the blood to avoid the development of hypotension and associated renal dysfunction.
The daily dose for non-insulin dependent diabetic patients suffering from hypertension is 10 mg per day in one portion. If necessary, the dose can be increased to 20 mg per day in order to achieve optimal diastolic pressure (should be below 90 mm Hg. Cm.).
Acute myocardial infarction.
In the case of lisinopril in the first 24 hours after infarction initial dose should be 5 mg per day, 24 hours later re prescribed 5 mg, after 48 hours - 10 mg, further maintenance dose is 10 mg per day. Duration of treatment - 6 weeks. If necessary, the treatment is carried out by a conventional circuit, in such cases, for example administered thrombolytic drugs, acetylsalicylic acid, and β-blockers.
Sistolitichnomu at low pressure (≤ 120 mm Hg. Cm.) Or during the first 3 days after myocardial shows the use of a low dose (2.5 mg / d), after which, if conditions allow the patient can continue treatment larger dose. In the case of arterial hypotension (.. Systolic pressure of ≤ 100 mm Hg) to reduce the recommended maintenance dose to 5 mg / day, if necessary - with an intermediate reduction * 2.5 mg / day.
The indications for treatment discontinuation lisinopril is hypotension, continues when one hour after the drug sistolitichny pressure remains below 90 mm Hg. Art.
With the development of heart failure should be observed for dosage instructions set out in the relevant section.
Patients with impaired renal function.
Since the elimination of lisinopril carried kidney initial dose depends on the performance of creatinine clearance, maintenance dose depends on the clinical response and is chosen with regular measurement of parameters of renal function, potassium and sodium concentration in the blood.
CC (ml / min)
Starting Dose (mg / day)
31 - 70
10 - 30
(Including patients on hemodialysis) *
5 - 10
2.5 - 5
Admission lisinopril can be stopped for the duration of dialysis.
If necessary to assign a dose of 2.5 mg apply the drug with a suitable dosage.
The dose and frequency of drug administration is determined by parameters lowering blood pressure.
The maximum dose of lisinopril is 40 mg / day.
Use in elderly patients
In clinical trials showed no difference in the efficacy or safety of treatment with lisinopril, depending on age. Since old age is often a decrease in kidney function, the dose should be defined, adopted in renal failure.
The use in patients with kidney transplant
Lisinopril experience with patients immediately after kidney transplantation have therefore assignment in these patients is not suitable for the preparation.
The drug is not used in children.
Data on overdose are limited people. Symptoms associated with overdose of ACE inhibitors may include hypotension, circulatory shock, electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.
Treatment is symptomatic.Also common measures for excretion from the body of lisinopril (gastric lavage, adsorbents and potassium sulfate for 30 minutes after administration of lisinopril) requires monitoring of vital signs and adjusting them in the ICU. It requires continuous monitoring of the level of electrolytes and creatinine concentrations in serum.
Registered in overdose treatment is administering a standard saline solution and replenishment fluid volume. If as a result of these measures the desired result was not achieved, it is necessary the introduction of catecholamines. It should also take into account the treatment of angiotensin II.
Bradycardia can be reduced by administering atropine. It is necessary to consider the installation of a pacemaker in the development of bradycardia resistant to treatment. Lisinopril can be removed from the general circulation by hemodialysis. During dialysis should be avoided polyacrylonitrile membranes with high flux density.
Side effects are usually mild and short-lived, treatment discontinuation is necessary in exceptional cases.
The following can be observed side effects, which are grouped into classes organs and frequency systems.
From the blood: suppression of bone marrow function, anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, haemolytic anemia, lymphadenopathy.
Immune system: autoimmune disease, angioedema.
From the Endocrine: syndrome of inappropriate secretion of ADH.
On the part of metabolism: hypoglycaemia.
From the nervous system: dizziness, headache, paresthesia, vertigo, taste disturbance, loss of consciousness.
On the part of the psyche: mood changes, sleep disturbances, confusion, depression.
Cardio-vascular system: palpitations, tachycardia, myocardial infarction (available as a complication of excessive hypotension in high-risk patients), orthostatic effects (including hypotension), cerebrovascular accident), possibly as a complication of excessive hypotension in high-risk patients), Raynaud's phenomenon .
The respiratory system: cough, inflammation of the mucous membranes of the nose, bronchospasm, sinusitis, allergic alveolitis, eosinophilic pneumonia.
On the part of the digestive tract: vomiting, diarrhea, nausea, abdominal pain, dyspepsia, dry mouth, pancreatitis, intestinal angioedema.
From the digestive system: hepatocellular or cholestatic jaundice, hepatitis, liver failure.
Skin: rash, itch, hypersensitivity / angioedema (face, extremities, lips, tongue, glottis and / or larynx), urticaria, alopecia, psoriasis, sweating, pemphigus, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, skin pseudolymphoma *.
From the urinary system: renal dysfunction, uremia, acute renal failure, oliguria / anuria.
Reproductive system: impotence, gynecomastia.
Systemic disorders and complications at the site of pain in the chest, fatigue, asthenia.
Changes in laboratory parameters: increase of urea, serum creatinine, elevated liver enzymes, hyperkalemia, increased hematocrit, decreased hemoglobin level, increase in serum bilirubin, hyponatraemia
* A complex of symptoms that can include both one and several manifestations: sensation of fever, pain in the muscles, joints, arthritis, vasculitis, eosinophilia, leukocytosis and / or positive response to antinuclear antibodies, acceleration of ESR, photosensitivity, rash. When developing a severe skin reaction, stop treatment with lisinopril and immediately consult a doctor.
The safety of preparations containing lisinopril also reported such adverse reactions: imbalance, disorientation, impaired sense of smell, glossitis, fainting, muscle spasms, dyspnea, upper respiratory tract infections, decreased appetite, constipation, skin hyperemia, proteinuria.
The safety data from clinical trials show that, in general, lisinopril is well tolerated by pediatric patients with hypertension, and the safety profile in this age group is comparable to the profile of a group of adult patients.
Store at a temperature of no higher than 25 ° C in the original packaging. Keep out of the reach of children.
For 14 tablets in a blister, 2 blisters in a carton.
For 15 tablets in a blister, 2 blisters in a carton.
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