Lisinopril-Teva, tablets 20 mg 30 pcs

Pharmacotherapeutic group: angiotensin-converting enzyme inhibitor
ATX code: C09AA03

Pharmacological properties

Pharmacodynamics. Angiotensin-converting enzyme (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 (TPR), 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 more than veins. Some effects are attributed to effects on the renin-angiotensin-aldosterone system (RAAS). Long-term use reduces myocardial hypertrophy and resistive arterial wall hypertrophy. It improves the blood supply to the ischemic myocardium.

The ACE inhibitors prolong life expectancy in patients with chronic heart failure (CHF), slow the progression of left ventricular dysfunction in patients who have had acute myocardial infarction without clinical manifestations of heart failure. Onset of action of the drug is within 1 hour, the maximum antihypertensive effect is achieved after 6-7 hours and is maintained for 24 hours. The duration of the effect also depends on the dose taken. In arterial hypertension, the effect is noted in the first days after the start of treatment, a stable effect develops after 1-2 months of therapy. No pronounced increase in BP was observed when lisinopril was abruptly withdrawn.

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

Pharmacokinetics

Intake. After oral administration, lisinopril is absorbed from the gastrointestinal tract (GIT) by an average of 25%, but absorption can vary from 6 to 60%. The bioavailability is 29%. Maximum plasma concentration (Cmax) is reached after 7 h. Food intake does not affect absorption of lisinopril.

Distribution. Lisinopril binds insignificantly to plasma proteins. Permeability through the blood-brain barrier and the placental barrier is low.

Metabolism. Lisinopril is not biotransformed in the body.

Elimation. It is excreted unchanged by the kidneys. The elimination half-life (T1/2) is 12.6 hours. Lisinopril clearance is 50 ml/min. Decrease in serum concentration of lisinopril occurs in two phases. The bulk of lisinopril is excreted during the initial alpha phase (effective T1/2- 12 h), followed by the terminal distant beta phase (about 30 h).

Pharmacokinetics in selected patient groups

In patients with CHF the absorption and clearance of lisinopril are reduced and the bioavailability is 16%.

In patients with renal insufficiency (creatinine clearance (CK) less than 30 ml/min), lisinopril concentrations are several times higher than plasma concentrations in
healthy volunteers, with increased time to reach Cmax in plasma and increased T1/2.

In elderly patients the plasma concentrations of the drug and the area under the curve “concentration-time” are twice as high as in younger patients.

In patients with cirrhosis the bioavailability of lisinopril is reduced by 30% and clearance by 50% compared to patients with normal liver function.

Indications

Active ingredient

Composition

1 tablet contains:

active ingredient: lisinopril dihydrate (lisinopril) – 21.84 mg (20.00 mg);

excipients: Pregelatinized starch 12.00 mg, corn starch 40.00 mg, calcium hydrophosphate (anhydrous) 73.96 mg, mannitol 70.00 mg, magnesium stearate 2.20 mg.

How to take, the dosage

Lisinopril-Teva is taken orally once a day, regardless of the time of meals, preferably at the same time of the day. The dose is chosen individually. In patients with arterial hypertension who do not receive other hypotensive agents, 5 mg per day is used. If there is no therapeutic effect, the dose is increased every 2-3 days by 5 mg to a dose of 20-40 mg/day (an increase in dose over 40 mg/day usually does not lead to further BP reduction).

The average daily maintenance dose is 20 mg. The maximum daily dose is 40 mg. Therapeutic effect usually develops in 2-4 weeks from the beginning of treatment, which should be taken into account when increasing the dose. If the effect is insufficient, concomitant use of the drug with other hypotensive agents is possible.

If the patient received prior treatment with diuretics, the administration of these drugs should be stopped 2-3 days before starting the drug Lisinopril-Teva. If this is not possible, the initial dose of Lisinopril-Teva should not exceed 5 mg per day. In this case after the first dose it is recommended to have a physician’s control for several hours (the maximum effect is reached after about 6 hours), since a marked decrease in BP may occur.

In renovascular hypertension associated with increased RAAS activity, a low initial dose of 2.5 mg per day should also be used in the follow-up, under increased medical monitoring (BP, renal function, serum potassium control). The maintenance dose, continuing close medical supervision, should be determined depending on the dynamics of BP.

In chronic heart failure, the initial dose of 2.5 mg per day, the dose is gradually increased (by no more than 10 mg, at intervals of at least 2 weeks) depending on BP. The maximum daily dose is 20 mg.

In early treatment of acute myocardial infarction, the dose is 5 mg in the first day, then 5 mg every other day, 10 mg after two days and then 10 mg daily 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 during the first 3 days after myocardial infarction in patients with low systolic blood pressure (120 mm Hg or less), a lower dose of 2.5 mg of Lisinopril-Teva should be used. It is not recommended to use Lisinopril-Teva if systolic blood pressure is lower or equal to 100 mmHg. In concomitant renal insufficiency (CKG less than 80 ml/min) the preparation dose should be corrected accordingly.

In diabetic nephropathy in patients with diabetes mellitus type 1,isinopril-Teva is used in dose of 10 mg daily. If necessary, the dose can be increased to 20 mg daily in order to achieve a diastolic BP below 75 mmHg in sitting position. In patients with type 2 diabetes mellitus, Lisinopril-Teva is used in the same dose to achieve a diastolic BP lower than 90 mmHg in sitting position.

The starting dose (mg/day)

30-80

5-10

10-29

2.5-5

less than 10 (including patients on hemodialysis)

2.5

In renal failure and in patients on hemodialysis, the starting dose is set depending on the CK. The maintenance dose is determined depending on BP (under control of renal function, blood potassium and sodium levels).

Interaction

Special Instructions

A pronounced decrease in BP most often occurs with a decrease in the blood pressure caused by diuretic therapy, reduction of dietary salt, dialysis, diarrhea, or vomiting. It is recommended to use Lisinopril-Teva under medical supervision in patients with CHD, cerebrovascular failure, where a sharp decrease in BP may lead to myocardial infarction or stroke. The use of the drug Lisinopril-Teva may lead to impaired renal function, acute renal failure, which is usually irreversible even after discontinuation of the drug.

Transient arterial hypotension is not a contraindication for further use of the drug.

. In case of renal artery stenosis (especially in bilateral stenosis or in presence of artery stenosis of single renal artery) as well as in peripheral circulatory failure due to hyponatremia and hypovolemia the use of this medicine may cause renal dysfunction, acute renal failure which is usually irreversible after drug withdrawal.

Lisinopril-Teva may be used simultaneously with standard therapy of acute myocardial infarction (thrombolytics, acetylsalicylic acid as an antiplatelet agent, beta-adrenoblockers).

Lisinopril-Teva may be used concomitantly with intravenous nitroglycerin or with therapeutic nitroglycerin transdermal systems.

The use of the drug Lisinopril-Teva is not recommended in patients who have had acute myocardial infarction if systolic blood pressure is less than 100 mm Hg. During surgical interventions, as well as during the use of other drugs that cause BP decrease, lisinopril, by blocking angiotensin II formation, may cause a significant unpredictable BP decrease. Before surgical intervention (including dental surgery), the surgeon/anesthesiologist should be informed about the use of an ACE inhibitor.

In elderly patients, the use of standard doses leads to higher blood concentrations of the drug; therefore, special caution is required when determining the dose, although no differences in the antihypertensive effect of Lisinopril-Teva in elderly and young patients were found.
Since the potential risk of agranulocytosis cannot be excluded, periodic peripheral blood monitoring is required.

Angioneurotic edema of the face, extremities, lips, tongue, epiglottis and/or larynx, which may occur during any period of treatment, has rarely been noted in patients taking ACE inhibitor, including lisinopril. In this case, treatment with the drug should be discontinued as soon as possible, and the patient should be monitored until the symptoms have completely regressed. Angioedema with laryngeal edema may be fatal. Tongue, epiglottis or pharyngeal edema may cause airway obstruction, so appropriate therapy (0.3-0.5 ml 1:1000 subcutaneous epinephrine (adrenaline) solution) and/or measures to ensure airway patency should be initiated immediately. In cases where the swelling is limited to the face and lips, the condition usually resolves without treatment, but antihistamines may be used. ACE inhibitors are more likely to cause angioedema in black patients than in other races. The risk of angioedema is increased in patients who have a history of angioedema unrelated to previous treatment with ACE inhibitors.

Patients taking ACE inhibitors during a desensitization procedure to hymenopteran venom, very rarely, may develop life-threatening anaphylactoid reactions. This can be avoided by temporarily discontinuing ACE inhibitor treatment before each hymenoptera desensitization procedure. Anaphylactoid reactions have also been reported in patients on hemodialysis using high flow dialysis membranes (AN69®) who are simultaneously taking ACE inhibitors. In such cases, another type of dialysis membrane or another hypotensive agent should be considered. In patients receiving oral hypoglycemic agents and insulin, blood glucose should be regularly monitored during the first month of therapy with ACE inhibitors.

A very rare syndrome has been observed with ACE inhibitors that began with cholestatic jaundice and progressed to fulminant liver necrosis, sometimes with a fatal outcome. The mechanism of this syndrome is unknown. If jaundice occurs during use of Lisinopril-Teva or marked increase in liver transaminase activity, the drug should be discontinued and the patient should be monitored.

Cough has been reported with ACE inhibitors. The cough is dry and prolonged, which disappears after discontinuation of ACE inhibitor treatment. In the differential diagnosis of cough, cough caused by ACE inhibitor use must also be considered.

Impact on driving and operating machinery

Cautions should be taken when taking Lisinopril-Teva due to the potential development of hypotension, dizziness and somnolence which may affect driving and operating potentially dangerous machinery.

Contraindications

Hypersensitivity to lisinopril, other drug components or other ACE inhibitors; history of angioedema (including from the use of other ACE inhibitors); hereditary Quincke’s edema and/or idiopathic angioedema; age under 18 years (effectiveness and safety not established); pregnancy and breastfeeding.

With caution:
Bilateral renal artery stenosis or artery stenosis of the single kidney with progressive azotemia; condition after renal transplantation; renal failure; hemodialysis using high-flow dialysis membranes (AN69®); azotemia; hyperkalemia; aortic stenosis; hypertrophic obstructive cardiomyopathy; primary hyperaldosteronism; arterial hypotension; cerebrovascular disease (including cerebrovascular insufficiency).including insufficiency of cerebral circulation); coronary heart disease (CHD); coronary insufficiency; autoimmune diseases of connective tissue (including scleroderma, systemic lupus erythematosus); inhibition of medullary hematopoiesis; conditions accompanied by a decrease in circulating blood volume (CBC) (including those due to diarrhea, vomiting); use in patients on diets with restriction of table salt; elderly patients; concomitant use with potassium preparations, diuretics, other hypotensive agents, nonsteroidal anti-inflammatory drugs (NSAIDs), lithium preparations, antacids, colestyramine, ethanol, insulin, other hypoglycemic drugs, allopurinol, procainamide, gold drugs, neuroleptics, tricyclic antidepressants, barbiturates, beta-adrenoblockers, slow calcium channel blockers.

Side effects

Overdose

Symptoms: marked BP decrease, dry mouth, water-electrolyte imbalance, renal failure, rapid breathing, tachycardia, palpitations, bradycardia, dizziness, anxiety, increased irritability, cough, drowsiness, urinary retention, constipation, collapse, hyperventilation of lungs.

Treatment: there is no specific antidote. Gastric lavage, use of enterosorbents and laxatives. Intravenous injection of 0.9% sodium chloride solution is indicated. In the case of treatment-resistant bradycardia, it is necessary to use an artificial “driver” of the rhythm. Necessary control of BP, indicators of water-electrolyte balance. Hemodialysis is effective.

Pregnancy use

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