Lisinopril-SZ tablets 20 mg, 50 pcs.

Pharmacotherapeutic group:

An angiotensin-converting enzyme (ACE) inhibitor;

ATX code: [C09AA03];

Pharmacological effect.

Pharmacodynamics:

ACE inhibitor, reduces angiotensin II formation 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 the minute blood volume and increases myocardial tolerance to exercise 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. 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 in the first days after the start of treatment, the stable effect develops after 1-2 months. No pronounced increase in BP was observed when the drug was abruptly withdrawn. In addition to BP reduction, Lisinopril reduces albuminuria. In patients with hyperglycemia, it normalizes 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 does not affect absorption of the drug. Bioavailability is 29%. Distribution. It is almost not bound to plasma proteins. Maximum plasma concentration (90 ng/ml) is achieved after 7 hours. Hematoencephalic and placental barrier permeability 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 individual groups of patients:

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

Indications

Active ingredient

Composition

Active substance:

lisinopril dihydrate corresponding to 20 mg lisinopril;

Auxiliary substances:

milk sugar (lactose);

calcium stearate.

Description:

The tablets 20 mg are white or almost white, flat-cylindrical shape, with a bevel and a rib.

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 received prior treatment with diuretics, it is necessary to stop taking these drugs 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), because 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 monitoring by a physician, 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.

Interaction

The concomitant use of the drug with potassium-saving diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium, cyclosporine increases the risk of hyperkalemia, especially with impaired renal function, so they may be used together only with regular monitoring of serum potassium ions and renal function.

The combined use of lisinopril with beta-adrenoblockers, “slow” calcium channel blockers (SCBs), diuretics, tricyclic antidepressants/neuroleptics and other hypotensive agents increases the severity of hypotensive effect.

Lisinopril slows down excretion of lithium preparations. Therefore, when using together it is necessary to monitor serum lithium concentration regularly.

Antacids and colestiramine decrease absorption of lisinopril in gastrointestinal tract.

When combined with insulin and hypoglycemic agents for oral administration, there may be a risk of hypoglycemia.

Non-steroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 (COX-2) inhibitors), estrogens, adrenomimetics decrease hypotensive effect of lisinopril.

In concomitant use of ACE inhibitors and intravenous gold drugs (sodium aurothiomalate), a symptom complex including facial hyperemia, nausea, vomiting and BP decrease has been described.

When coadministered with selective serotonin reuptake inhibitors, it may lead to severe hyponatremia.

Concomitant use with allopurinol, procainamide, cytostatics may lead to leukopenia.

Special Instructions

Symptomatic hypotension

Most often a pronounced decrease in BP occurs with a decrease in circulating blood volume (CBC) caused by diuretic therapy, reduction of table salt in food, dialysis, diarrhea or vomiting. In patients with chronic heart failure with or without concomitant renal insufficiency, marked BP reduction is possible.
Under close medical supervision, Lisinopril should be used in patients with coronary heart disease, cerebrovascular insufficiency, in whom a sharp decrease in BP may lead to myocardial infarction or stroke. Transient arterial hypotension is not a contraindication for the next dose of the drug.

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

Before initiating treatment with the drug, if possible, sodium should be normalized and/or the BOD 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 with bilateral stenosis or in presence of artery stenosis of single kidney) as well as in circulatory failure due to lack of sodium ions and/or fluid, use of Lisinopril may lead to renal dysfunction, acute renal failure, which is usually irreversible even after drug withdrawal.

In acute myocardial infarction

The use of 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 pronounced unpredictable decrease in BP during major surgical interventions, as well as during the use of other agents that cause BP reduction.
In elderly patients, the same dose leads to higher blood concentrations of the drug, so special caution is required in determining the dose.

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

Impact on driving and operating ability

There are no data about the effect of the drug Lisinopril on the ability to drive vehicles and operate mechanisms when used in therapeutic doses, but it should be taken into account that at the beginning of treatment arterial hypotension may occur, which may affect the ability to drive vehicles and operate potentially dangerous mechanisms, and dizziness and somnolence may occur, therefore 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.

Side effects

The most common side effects: dizziness, headache, increased fatigue, diarrhea, dry cough, nausea.

– Cardiovascular system: marked BP decrease, chest pain, rarely – orthostatic hypotension, tachycardia, bradycardia, worsening of symptoms of heart failure, atrioventricular conduction disorder, myocardial infarction, palpitations.

– Central nervous system: mood lability, confusion, paraesthesia, somnolence, convulsive twitching of the muscles of the limbs and lips, rarely – asthenic syndrome.

– Blood system disorders: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, anemia (decreased concentration of hemoglobin, hematocrit, erythrocytopenia).

– Laboratory parameters: hyperkalemia, hyponatremia, rarely – increased liver enzymes activity, hyperbilirubinemia, increased urea and creatinine.

– Respiratory system: dyspnea, bronchospasm.

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

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

– Urinary system disorders: renal dysfunction, oliguria, anuria, acute renal failure, uremia, proteinuria, decreased potency. Allergic reactions: angioedema of the face, extremities, lips, tongue, epiglottis and/or larynx, skin rash, itching, fever, positive results of antinuclear antibody test, increased erythrocyte sedimentation rate (ESR), eosinophilia, leukocytosis.

In very rare cases – interstitial angioedema.

– Other: myalgia, arthralgia/arthritis, vasculitis.

Overdose

Symptoms (occurs with a single dose of 50 mg or more): marked BP decrease; dry mouth, drowsiness, urinary retention, constipation, restlessness, increased irritability.

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

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