Lisinopril-Vertex, tablets 10 mg 30 pcs

Lisinopril is cardioprotective, natriuretic, vasodilatory, hypotensive.

Pharmacodynamics

A ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. Decreased angiotensin II leads to a direct reduction in aldosterone release. Reduces bradykinin degradation and increases prostaglandin synthesis. Reduces total peripheral vascular resistance, blood pressure (BP), preload, pulmonary capillary pressure, causes an increase in minute blood volume and increases myocardial exercise tolerance in patients with chronic heart failure. Dilates arteries to a greater extent than veins. Some effects are explained by the effect on tissue renin-angiotensin systems. Long-term use reduces myocardial hypertrophy and resistive arterial wall hypertrophy. It improves the blood supply to the ischemic myocardium.

ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure. The antihypertensive effect begins after approximately 6 hours and lasts for 24 hours. The duration of the effect also depends on the dose. The onset of action is in 1 hour. The maximum effect is determined after 6-7 hours. In case of arterial hypertension, the effect is noted during the first days after the start of treatment, the stable effect develops after 1-2 months. At acute withdrawal of the drug no pronounced increase in BP was observed.
In addition to BP reduction, lisinopril decreases albuminuria. In patients with hyperglycemia it helps to normalize the function of the damaged glomerular endothelium.

Lisinopril does not affect blood glucose concentration in diabetic patients and does not lead to increased incidence of hypoglycemia.

Pharmacokinetics

Intake. After oral administration about 25% of lisinopril is absorbed from the gastrointestinal tract. Food intake has no effect on absorption of the drug. Absorption is on average 30%, bioavailability is 29%.

Distribution. Almost does not bind with blood plasma proteins. Maximal concentration in blood plasma (90 ng/ml) is reached after 7 hours. Permeability through the blood-brain and placental barrier is low.

Metabolism. Lisinopril is not biotransformed in the body.
Excretion. It is excreted unchanged by the kidneys. Half-life period is 12 hours.

Pharmacokinetics in selected groups of patients

In patients with chronic heart failure absorption and clearance of lisinopril are decreased.
In patients with renal failure, lisinopril concentrations are several times higher than plasma concentrations in volunteers, with increased time to reach maximum plasma concentration and increased elimination half-life.
In elderly patients the plasma concentration of the drug and area under the curve are 2 times higher than in younger patients.

Indications

• Arterial hypertension (in monotherapy or in combination with other antihypertensive agents);
• Cronic heart failure (as part of combination therapy to treat patients taking hypertensive drugs and/or diuretics);
• Diabetic nephropathy (decrease of albuminuria in insulin dependent patients with normal BP and insulin independent patients with hypertension).

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Active ingredient

Lisinopril

Composition

Active ingredient:

lisinopril dihydrate;

Excipients:

Milk sugar (lactose),

Microcrystalline cellulose,

Starch 1500 (gelatinized), <

aerosil (colloidal silicon dioxide),

talc,

magnesium stearate

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How to take, the dosage

Ingestion, regardless of meals. In patients with arterial hypertension who are not receiving other hypotensive agents, 5 mg once daily is prescribed. If there is no effect, the dose is increased every 2-3 days by 5 mg to an average therapeutic dose of 20-40 mg/day (an increase in dose over 40 mg/day usually does not lead to further BP reduction). 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. In case of insufficient clinical effect it is possible to combine the drug with other hypotensive agents.

If the patient has received prior treatment with diuretics, these drugs should be discontinued 2-3 days before starting Lisinopril. If this is not feasible, the initial dose of Lisinopril should not exceed 5 mg per day. In this case, after the first dose it is recommended that the physician controls for several hours (the maximum effect is reached after about 6 hours), since a marked decrease in BP may occur.

In renovascular hypertension or other conditions with increased activity of renin-angiotensin-aldosterone system it is reasonable to prescribe also low initial dose – 2.5-5 mg per day, under increased medical control (BP control, renal function, serum potassium concentration). The maintenance dose, while continuing close medical supervision, should be determined depending on the dynamics of BP.
In renal failure, due to the fact that lisinopril is excreted through the kidneys, the initial dose should be determined according to creatinine clearance, then according to the response, a maintenance dose should be established with frequent monitoring of renal function, serum potassium, sodium levels.

In persistent arterial hypertension, long-term maintenance therapy at 10-15 mg/day is indicated.
In chronic heart failure – start with 2.5 mg once daily, with subsequent dose increases by 2.5 mg after 3-5 days to the usual, maintenance daily dose of 5-20 mg. The dose should not exceed 20 mg daily.

Elderly people often have a more pronounced long-term hypotensive effect, which is associated with decreased excretion rate of lisinopril (it is recommended to start treatment with 2.5 mg/day).
Acute myocardial infarction (as part of combined therapy)

In the first day – 5 mg orally, then 5 mg every other day, 10 mg two days and then 10 mg once daily. In patients with acute myocardial infarction the drug should be used for at least 6 weeks.

At the beginning of treatment or during the first 3 days after acute myocardial infarction in patients with low systolic blood pressure (120 mm Hg or lower) a lower dose of 2.5 mg should be prescribed. In case of BP decrease (systolic BP below or equal to 100 mmHg), the daily dose of 5 mg may be temporarily reduced to 2.5 mg, if necessary. In case of prolonged marked BP lowering (systolic BP below 90 mmHg for more than 1 hour), treatment with Lisinopril should be stopped.

Diabetic nephropathy
In patients with insulin-independent diabetes mellitus 10 mg of Lisinopril once daily is used. The dose can be increased up to 20 mg
once a day if necessary in order to achieve diastolic BP values below 75 mmHg in sitting position. The dosage is identical in patients with insulin-dependent diabetes mellitus in order to achieve values of diastolic BP lower than 90 mmHg at sitting position.

Interaction

Lisinopril decreases potassium excretion when treated with diuretics.
Special caution is required when using the drug concomitantly with:

• kali-saving diuretics (spironolactone, triamterene, amiloride), potassium, table salt substitutes containing potassium (increased risk of hyperkalemia, especially in impaired renal function), so they can be prescribed together only on the basis of an individual decision of the treating doctor with regular monitoring of serum potassium and renal function.

Cautiously may be used with:

• with diuretics: When an additional diuretic is administered to a patient taking Lisinopril, there is usually an additive antihypertensive effect – the risk of a pronounced decrease in BP;
• with other antihypertensive agents (additive effect);
• with nonsteroidal anti-inflammatory drugs (indomethacin, etc.), estrogens, as well as adrenostimulants – decrease antihypertensive effect of lisinopril;
• with lithium (lithium excretion may decrease, therefore serum lithium concentration should be regularly monitored);
• with antacids and colestyramine – reduce absorption in the gastrointestinal tract.

Alcohol increases the effect of the drug.

Special Instructions

Symptomatic hypotension

Most often a pronounced decrease in BP occurs with a decrease in fluid volume caused by diuretic therapy, reduction of salt in food, dialysis, diarrhea or vomiting. In patients with chronic heart failure with or without concomitant renal failure, pronounced BP reduction is possible. It is more often found in patients with severe stage of chronic heart failure, as a consequence of high doses of diuretics, hyponatremia or impaired renal function. In such patients treatment with Lisinopril should be started under close supervision of physician (choose the dose of drug and diuretics with caution).

Similar rules should be followed when prescribing to patients with coronary heart disease, cerebrovascular insufficiency, in whom a sharp decrease in BP may lead to myocardial infarction or stroke.

Transient hypotensive reaction is not a contraindication for the next dose of the drug.

When using Lisinopril, some patients with chronic heart failure but with normal or lower BP may experience a decrease in BP, which is not usually a reason to discontinue treatment.

Before starting treatment with Lisinopril, if possible, sodium concentration should be normalized and/or lost fluid volume should be replenished and the effect of the initial dose of Lisinopril on the patient should be carefully monitored.

In case of renal artery stenosis (especially in bilateral stenosis, or in the presence of artery stenosis of the only kidney), as well as in circulatory failure due to lack of sodium and/or fluid, use of Lisinopril may also lead to impaired renal function, acute renal failure, which usually prove irreversible after withdrawal of the drug.

In acute myocardial infarction
Standard therapy (thrombolytics, acetylsalicylic acid, beta-adrenoblockers) is indicated. Lisinopril may be used in conjunction with intravenous or therapeutic nitroglycerin transdermal systems.

Surgery/general anesthesia
Lisinopril, by blocking angiotensin II formation, may cause a marked, unpredictable decrease in BP during major surgical interventions, as well as during the use of other drugs that cause BP reduction.

In elderly patients, the same dose leads to higher blood concentrations of the drug, so extra caution is required in determining the dose.

Because the potential risk of agranulocytosis cannot be excluded, periodic monitoring of blood counts is required. Anaphylactic shock may occur when the drug is used in dialysis with a polyacrylonitrile membrane, so either a different type of dialysis membrane or administration of other antihypertensive agents is recommended.

Effect on driving and operating ability

There are no data on the effect of lisinopril on driving and operating ability used in therapeutic doses, but it should be taken into account that dizziness may occur, so caution should be exercised.

Contraindications

Hypersensitivity to lisinopril or other ACE inhibitors, history of angioedema, including from use of ACE inhibitors, hereditary Quincke’s edema, age under 18 years (effectiveness and safety not established).

With caution: Severe renal dysfunction, bilateral renal artery stenosis or artery stenosis of the single kidney with progressive azotemia, condition after renal transplantation, renal failure, azotemia, hyperkalemia, aortic orifice stenosis, hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, arterial hypotension, cerebrovascular disease (includingincluding insufficiency of cerebral circulation), coronary heart disease, coronary insufficiency, autoimmune systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus); inhibition of bone marrow hematopoiesis; sodium-restricted diet: hypovolemic conditions (including those resulting from diarrhea, vomiting); old age.

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Side effects

Often: dizziness, headache (in 5-6% of patients), weakness, diarrhea, dry cough (3%), nausea, vomiting, orthostatic hypotension, skin rash, chest pain (1-3%).

Immune system disorders: (0.1%) angioedema (face, lips, tongue, larynx or epiglottis, upper and lower extremities).

Cardiovascular system: marked BP decrease, orthostatic hypotension, renal dysfunction, heart rhythm disorders, palpitations.

As to the central nervous system: increased fatigue, somnolence, convulsive twitching of the muscles of the limbs and lips.

Hematopoietic system disorders: leukopenia, neutropenia, agranulocytosis, thrombocytopenia are possible; with prolonged treatment – a slight decrease in hemoglobin concentration and hematocrit, erythrocytopenia.

Laboratory parameters: hyperkalemia, azotemia, hyperuricemia, hyperbilirubinemia, increased activity of “liver” enzymes, especially if there is a history of renal disease, diabetes and renovascular hypertension.

Rarely

Cardiovascular system: palpitation; tachycardia; myocardial infarction; cerebrovascular stroke in patients at increased risk due to marked BP reduction.

Gastrointestinal tract: dry mouth, anorexia, dyspepsia, changes in taste, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

Skin disorders: urticaria, increased sweating, itching, alopecia.

Urinary system disorders: renal dysfunction, oliguria, anuria, acute renal failure, uremia, proteinuria.

Immune system disorders: syndrome including accelerated erythrocyte sedimentation rate (ESR), arthralgia and the appearance of antinuclear antibodies.

Central nervous system: asthenic syndrome, mood lability, confusion, decreased potency.

Others: myalgia, fever, impaired fetal development.

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Overdose

Symptoms (occur with a single dose of 50 mg or more):

pronounced decrease in BP; dry mouth, drowsiness, delayed urination, constipation, restlessness, increased irritability.

Treatment:

symptomatic therapy, intravenous fluid administration, control of BP, water-electrolyte balance and its normalization.
Lisinopril may be eliminated from the body by hemodialysis.

Similarities

Diroton, Lisinopril, Lisinopril Stada, Lisinopril-Teva, Lisinopril-ALSI