Lisinopril - an inhibitor of the angiotensin-converting enzyme (ACE), which reduces the formation of angiotensin II from angiotensin I.
Release form and composition
Lisinopril dosage form - tablets: flat, round, with beveled edges, with a risk on one of the sides (10 pieces in blisters, 2, 3, 4, 5 or 6 packs in a cardboard box; 14 in blisters Cell packs, in carton packs of 1, 2, 3 or 4 packs).
The active ingredient of the drug is lisinopril in the form of dihydrate. Its content in tablets depending on color:
- Dark orange - 2.5 mg;
- Orange - 5 mg;
- Pink - 10 mg;
- White or almost white - 20 mg.
Auxiliary components: lactose monohydrate, corn starch, methylene chloride, povidone, magnesium stearate. In the tablets of 2.5 and 5 mg, in addition, the dye contains a sunset sunburst yellow, in tablets of 10 mg - the dye azorubine, in tablets of 20 mg - titanium dioxide.
Indications for use
- Early (in the first 24 hours) treatment of acute myocardial infarction in patients with stable hemodynamic parameters (as part of combination therapy in order to maintain these indicators and prevent heart failure and left ventricular dysfunction);
- Chronic heart failure (as part of complex therapy);
- Renovascular and essential arterial hypertension (as a single agent or in combination with other antihypertensive drugs);
- Diabetic nephropathy (to reduce albuminuria in patients with diabetes mellitus type I with normal blood pressure and patients with diabetes mellitus type II with arterial hypertension).
- Hereditary idiopathic edema or angioedema; angioedema;
- Angioedema in history, including as a result of the use of ACE inhibitors;
- Lactose intolerance, glucose-galactose malabsorption, lactase deficiency;
- Age up to 18 years;
- Hypersensitivity to the components of the drug or other ACE inhibitors.
Relative (special caution required):
- Elderly age;
- Hypertrophic obstructive cardiomyopathy;
- Aortic stenosis;
- Severe chronic heart failure;
- Coronary heart disease;
- Cerebrovascular diseases (including cerebrovascular insufficiency);
- Oppression of bone marrow hematopoiesis;
- Primary hyperaldosteronism;
- Systemic diseases of the connective tissue (including scleroderma and systemic lupus erythematosus);
- Hypovolemic states (including diarrhea and vomiting);
- Bilateral renal artery stenosis or arterial stenosis of a single kidney, severe renal failure (creatinine clearance less than 30 ml / minute), condition after kidney transplantation;
- Hemodialysis, which uses high-flow dialysis membranes (AN69).
Dosing and Administration
Lisinopril should be taken orally once a day, regardless of the meal, but preferably at the same time of day.
Treatment of essential hypertension begins with a daily dose of 10 mg. Maintenance dose - 20 mg, maximum daily - 40 mg. With increasing doses, it is important to consider that a stable hypotensive effect develops after 1-2 months of therapy. If, while taking the maximum daily dose, the therapeutic effect is not enough, the additional prescription of another antihypertensive agent is possible. Patients receiving pre-diuretics, for 2-3 days before the appointment of this drug should be canceled. If this is not possible, then the initial dose of Lisinopril should not exceed 5 mg per day.
The initial dose in renovascular hypertension and other conditions with increased activity of the renin-angiotensin-aldosterone system is 2.5-5 mg per day. The treatment is carried out under the control of kidney function, blood pressure (BP), the content of potassium in the blood serum. The doctor determines the maintenance dose based on the value of blood pressure. In chronic renal failure, the daily dose is set depending on creatinine clearance (CK): with CK 30-70 ml / minute - 5-10 mg, with CK 10-30 ml / minute - 2.5-5 mg, with CK less than 10 ml / minute and patients on hemodialysis - 2.5 mg. Maintenance dose depends on blood pressure.
Treatment of chronic heart failure begins with a dose of 2.5 mg per day (simultaneously with cardiac glycosides and / or diuretics). With intervals of 3-5 days, it is gradually increased by 2.5 mg to achieve a maintenance dose of 5-10 mg per day. The maximum permissible daily dose is 20 mg. If possible, before starting Lisinopril, the dose of diuretic should be reduced.
Older people often have a more pronounced long-term hypotensive effect, so treatment is recommended to start with a daily dose of 2.5 mg. In acute myocardial infarction, in the first 24 hours, 5 mg is prescribed, in a day - 5 mg, in another two days - 10 mg and then in 10 mg once a day, the minimum course of treatment is 6 weeks. In the case of a decrease in systolic pressure to 100 mm Hg. st. and lower the dose to 2.5 mg. With a prolonged (over 1 hour) marked decrease in systolic pressure below 90 mm Hg. st. the drug is canceled. Patients with low systolic pressure (120 mmHg and below) for the first 3 days after acute myocardial infarction or at the beginning of therapy Lisinopril is prescribed at a dose of 2.5 mg.
The initial dose for diabetic nephropathy is 10 mg per day. If necessary, it is increased to 20 mg: in order for patients with diabetes mellitus type I to achieve a diastolic pressure lower than 75 mm Hg. Art., and in patients with diabetes mellitus type II - below 90 mm Hg. st. (pressure measured in sitting position).
The most common side effects are fatigue, headache, dizziness, nausea, diarrhea, dry cough.
- Cardiovascular system: marked reduction in blood pressure, bradycardia, tachycardia, feeling of heartbeat, chest pain, impaired atrioventricular conduction, the appearance or worsening of symptoms of heart failure, orthostatic hypotension, myocardial infarction;
- Central nervous system: convulsive twitching of the lips and muscles of the extremities, paresthesias, asthenic syndrome, impaired concentration of attention, increased fatigue, emotional lability, drowsiness, confusion;
- The digestive system: changes in taste, dryness of the oral mucosa, abdominal pain, dyspepsia, anorexia, jaundice (cholestatic or hepatocellular), pancreatitis, hepatitis;
- Urogenital system: anuria, oliguria, proteinuria, uremia, impaired renal function, acute renal failure, reduced potency;
- Respiratory system: dry cough, dyspnea, bronchospasm;
- Hematopoietic system: agranulocytosis, neutropenia, thrombocytopenia, leukopenia, anemia (erythropenia, a decrease in the concentration of hemoglobin, hematocrit);
- Skin: photosensitivity, alopecia, increased sweating, pruritus;
- Allergic reactions: angioedema of the extremities, face, lips, tongue, epiglottis and / or larynx, skin rash, urticaria, increased ESR, fever, eosinophilia, positive test results for antinuclear antibodies, leukocytosis, intestinal angioedema;
- Other: arthralgia / arthritis, myalgia, vasculitis;
- Laboratory indicators: increased activity of hepatic transaminases, hyperbilirubinemia, hyponatremia, hypercreatininemia, hyperkalemia, increased urea concentration.
With simultaneous use of a gold preparation (sodium aurothiomalate) intravenously with an ACE inhibitor, a symptom complex has been described, including nausea and vomiting, facial flushing, arterial hypotension.
Lisinopril is contraindicated in cardiogenic shock and acute myocardial infarction, if a vasodilator can significantly worsen hemodynamic parameters, for example, when systolic BP is less than 100 mm Hg. st.
A pronounced decrease in blood pressure during administration of the drug most often occurs in the case of a decrease in circulating blood volume (BCC) caused by the use of diuretics, diarrhea or vomiting, hemodialysis, a decrease in the amount of salt in food. Patients with chronic heart failure also have a risk of marked reduction in blood pressure. More often, it is detected in patients with severe chronic heart failure as a result of hyponatremia, impaired renal function, or receiving high-dose diuretics. At the beginning of treatment, the described categories of patients should be under strict medical supervision; the selection of doses of Lisinopril and diuretics should be carried out with extreme caution. Similar rules must be followed when prescribing the drug to patients with coronary heart disease and cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to a stroke or myocardial infarction. Before therapy, it is recommended to normalize the concentration of sodium in the blood and / or replenish the BCC, then carefully monitor the effect of the initial dose of the drug.
In the treatment of symptomatic arterial hypotension, bed rest should be provided, if necessary, intravenous fluids (saline) should be prescribed. Transient arterial hypotension is not a contraindication to lisinopril, but may require a dose reduction or discontinuation of the drug.
Reduced kidney function (plasma creatinine concentration of more than 177 µmol / L and / or proteinuria of more than 500 mg / 24 hours) in patients with acute myocardial infarction is a contraindication to the use of Lisinopril. With the development of renal failure (the concentration of creatinine in the blood plasma is more than 265 µmol / l or 2 times the initial level) during treatment with this drug, the doctor decides whether to stop treatment.
Angioedema of the extremities, face, tongue, lips, epiglottis and / or larynx is rare, but may occur at any time during therapy. In this case, treatment should be stopped immediately and careful monitoring of the patient should be established until the symptoms are fully regressed. Laryngeal edema can be fatal. If the larynx, epiglottis or tongue is covered, airway obstruction is possible, therefore urgent appropriate therapy and / or measures to ensure the airway are needed.
When treating with ACE inhibitors, there is a potential risk of agranulocytosis, therefore it is necessary to monitor the blood picture.
In case of increased activity of hepatic transaminases or the appearance of cholestasis symptoms, the drug should be discontinued, since there is a risk of cholestatic jaundice, progressing to fulminant necrosis of the liver.
The entire period of therapy should refrain from the use of alcoholic beverages, as well as be careful in hot weather and during exercise, because possible development of dehydration and excessive reduction of blood pressure.
According to epidemiological studies, the simultaneous use of ACE inhibitors with insulin or oral hypoglycemic agents can lead to the development of hypoglycemia, especially during the first weeks of combination therapy, as well as in patients with impaired renal function. For this reason, glycemia should be carefully controlled in patients with diabetes mellitus, especially the first month of Lisinopril.
In the event of side effects from the central nervous system, it is recommended to refrain from driving and performing potentially dangerous types of work.
Beta-blockers, diuretics, slow calcium channel blockers and other antihypertensive agents enhance the hypotensive effect of Lisinopril.
With the simultaneous use of potassium supplements, salt substitutes containing potassium or potassium-saving diuretics (amiloride, triamterene, spironolactone), the risk of hyperkalemia increases, especially in patients with impaired renal function. For this reason, only a doctor should prescribe such a combination, and treatment should be carried out under constant monitoring of renal function and serum potassium concentration.
With the simultaneous use of vasodilators, barbiturates, tricyclic antidepressants, phenothiazine and ethanol, the antihypertensive effect of Lisinopril is enhanced. Antacids and colestyramine reduce its absorption from the gastrointestinal tract.
Nonsteroidal anti-inflammatory drugs (including selective cyclooxygenase-2 inhibitors), adrenostimulants and estrogens reduce the hypotensive effect of the drug.
Lisinopril with simultaneous use slows down the elimination of lithium from the body, which increases its cardiotoxic and neurotoxic effects.
Combined use with methyldopa can lead to hemolysis; with selective serotonin reuptake inhibitors - to severe hyponatremia; with cytostatics, procainamide, allopurinol - to leukopenia.
Lisinopril enhances the action of peripheral muscle relaxants, reduces the effectiveness of oral contraceptives, reduces the excretion of quinidine, enhances the neurotoxicity of salicylates, reduces the effect of oral hypoglycemic drugs, epinephrine (adrenaline), norepinephrine (noradrenaline) and anti-inflammatory drugs; enhances the effects (including side) of cardiac glycosides.
With simultaneous use of lizinopril with gold preparations may develop facial hyperemia, nausea and vomiting, arterial hypotension.
Terms and conditions of storage
Store at temperatures up to 25 ºС protected from moisture and light, out of reach of children.
Shelf life - 3 years.