Liten - instructions for use, doses, side effects, contraindications

Composition:Liten® 5 mg
Active substance: lisinopril dihydrate 5.444 mg, which corresponds to 5,000 mg of lisinopril.
Excipients: calcium hydrophosphate dihydrate 61,780 mg, mannitol 20,600 mg, starch corn 13,050 mg, pregelatinized starch 2,200 mg, magnesium stearate 1,550 mg, talc 1,000 mg, silicon dioxide colloid 0,500 mg.
Liten® 10 mg
Active substance: lisinopril dihydrate 10.888 mg, which corresponds to 10,000 mg of lisinopril.
Excipients: calcium hydrophosphate dihydrate 121,600 mg, mannitol 41,200 mg, maize starch 28,000 mg, pregelatinized starch 4,000 mg, magnesium stearate 3,100 mg, talc 2,000 mg, silicon dioxide colloid 1,000 mg, iron oxide pigment yellow 0.500 mg (E172).
Liten® 20 mg
Active substance: lisinopril dihydrate 21,776 mg, which corresponds to 20,000 mg of lisinopril.
Excipients: calcium hydrophosphate dihydrate 123,500 mg, mannitol 41,200 mg, starch corn 28,000 mg, starch pregelatinized 4,500 mg, magnesium stearate 3,100 mg, talc 2,000 mg, silicon dioxide colloid 1,000 mg, iron oxide oxide yellow 0.136 mg (E172), iron dye oxide red 0.045 mg (E172).

Description:Tablets 5 mg
Round, white tablets with a flat surface and a risk in the middle.
Tablets 10 mg
Yellow, round tablets with a flat surface and a risk in the middle.
Tablets 20 mg
Round, from light pink to pink color tablets with a flat surface and a risk in the middle.

Pharmacotherapeutic group:Angiotensin-converting enzyme inhibitor (ACE).

ATX: & nbsp

C.09.A.A.03 Lisinopril

C.09.A.A ACE Inhibitors

Pharmacodynamics:ACE inhibitor, reduces the formation of angiotensin II from angiotensin I.Reduction of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the overall peripheral vascular resistance, arterial pressure (AD), preload on the heart, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and increased tolerance of the myocardium to loads in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by the effect on the tissue renin-angiotensin-aldosterone system. With prolonged use, myocardial hypertrophy and the walls of arteries of resistive type decrease. Improves the blood supply of the ischemic myocardium.
ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients who underwent myocardial infarction without clinical manifestations of heart failure. Antihypertensive effect begins in 1 hour. The maximum antihypertensive effect is achieved after 6 hours and persists for 24 hours.The duration of the effect also depends on the size of the dose. With arterial hypertension, the effect is observed in the first days after the start of treatment, stable action develops after 1-2 months. With a sharp withdrawal of the drug, no pronounced increase in blood pressure was observed.
In addition to reducing blood pressure lisinopril reduces albuminuria. Lisinopril does not affect the concentration of glucose in the blood in patients with diabetes mellitus and does not increase the incidence of hypoglycemia.

Pharmacokinetics:Suction
After oral administration lisinopril absorbed from the gastrointestinal tract (GIT) on average by 25%, but the absorption can vary from 6 to 60%. Bioavailability is 25%. Eating does not affect the absorption of lisinopril.
Distribution
Almost does not bind to blood plasma proteins.
The maximum concentration in blood plasma (90 ng / ml) is achieved after 7 hours. Permeability through the blood-brain and placental barrier is low.
Metabolism
Lizinopril is not biotransformed in the body.
Excretion
It is excreted by the kidneys unchanged. The half-life is 12 hours.
Pharmacokinetics in selected patient groups
In patients with chronic heart failure, the absorption and clearance of lisinopril are reduced, bioavailability is 16%.
In patients with renal insufficiency, the concentration of lisinopril is several times higher than the plasma concentration in healthy volunteers, with an increase in the time to reach the maximum concentration in the blood plasma and an increase in the half-life.
In elderly patients, the concentration of the drug in the blood plasma and the area under the "concentration-time" curve is 2 times greater than in young patients.

Indications:Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs).
Chronic heart failure (as part of combination therapy for the treatment of patients taking cardiac glycosides and / or diuretics).
Early treatment of acute myocardial infarction as part of combination therapy (in the first 24 hours with stable hemodynamic parameters to maintain these parameters and prevention of left ventricular dysfunction and heart failure). Diabetic nephropathy (a decrease in albuminuria in patients with type 1 diabetes mellitus with normal BP, and patients with type 2 diabetes mellitus with arterial hypertension).

Contraindications:Hypersensitivity to lisinopril, other ACE inhibitors or drug auxiliaries, history of angioedema, including the use of ACE inhibitors, hereditary Quincke edema or idiopathic edema, age under 18 years (efficacy and safety not established).

Carefully:Severe renal dysfunction, bilateral renal artery stenosis or arterial stenosis of a single kidney with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia, aortic aortic stenosis, hypertrophic obstructive cardiomyocathy, primary hyperaldosteronism, arterial hypotension, cerebrovascular diseases (including cerebral circulatory insufficiency ), ischemic heart disease, coronary insufficiency, autoimmune systemic connective tissue diseases (including chi le scleroderma, systemic lupus erythematosus); oppression of bone marrow hematopoiesis; diet with restriction of table salt; hypovolemic conditions (including as a result of diarrhea, vomiting); old age, hemodialysis using high-permeability dialysis membranes with high permeability (AN69®).

Pregnancy and lactation:The use of Liten® during pregnancy is not recommended. When diagnosing pregnancy, taking the drug should be stopped as soon as possible. Admission of ACE inhibitors in the II and III trimester of pregnancy has an adverse effect on the fetus (there may be a marked decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, fetal death). Data on the negative effects of the drug on the fetus in case of application during the I trimester are not present. For newborns and infants who have undergone intrauterine exposure to ACE inhibitors, careful monitoring is recommended to timely detect a marked decrease in blood pressure, oliguria, and hyperkalemia.
Lizinopril penetrates the placenta. There is no data on the penetration of lisinopril into breast milk. For the period of treatment with Liten®, breastfeeding should be abolished.

Dosing and Administration:Inside, 1 time per day, regardless of food intake, preferably at the same time. With arterial hypertension, patients who do not receive other antihypertensives, Liten®, are prescribed 5 mg once a day.In the absence of effect, the dose is increased every 2-3 days by 5 mg to an average therapeutic dose of 20-40 mg / day (increasing the dose above 40 mg / day usually does not lead to a further decrease in blood pressure). 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. If the clinical effect is insufficient, it is possible to combine Liten® with other antihypertensive drugs.
If the patient received pre-treatment with diuretics, the medication should be stopped 2-3 days before the Liten® drug is started. If this is not possible, then the initial dose of the drug should not exceed 5 mg per day. In this case, after taking the first dose, medical supervision is recommended for several hours (maximum effect is achieved after about 6 hours), since there may be a pronounced decrease in blood pressure.
In the case of renovascular hypertension or other conditions with increased activity of the renin-angiotensin-aldosterone system (RAAS), it is also advisable to prescribe a low initial dose of 2.5-5 mg per day (1/2 tablets of 5 mg - 1 tablet), under enhanced medical supervision (control of blood pressure, kidney function, potassium content in blood serum).The maintenance dose, continuing strict medical control, should be determined depending on the dynamics of blood pressure.
With renal failure due to the fact that lisinopril is released through the kidneys, the initial dose should be determined according to the creatinine clearance, then, in accordance with the reaction, a maintenance dose should be established in conditions of frequent monitoring of kidney function, potassium, sodium in the blood serum.

Creatinine clearance, ml / min	Initial dose of lisinopril, mg per day
30-70	5-10
10-30	2,5-5
less than 10	2,5

(including patients on hemodialysis)
With persistent arterial hypertension, prolonged maintenance therapy of 10-15 mg / day is shown.
For chronic heart failure, start with 2.5 mg (1/2 tablets 5 mg) once a day, followed by a 2.5 mg dose increase (1/2 tablets 5 mg) 3-5 days before the usual , supporting a daily dose of 5-20 mg. The dose should not exceed 20 mg per day.
Elderly people often have a more pronounced prolonged antihypertensive effect, which is associated with a decrease in the rate of excretion of lisinopril (it is recommended to start treatment with 2.5 mg / day (1/2 tablets of 5 mg)).Acute myocardial infarction (as part of combination therapy)
On the first day - 5 mg orally, then 5 mg every other day, 10 mg after two days and then 10 mg once a day. In patients with acute myocardial infarction, the drug should be applied for at least 6 weeks.
At the beginning of treatment or within the first 3 days after an acute myocardial infarction in patients with low systolic BP (120 mm Hg or lower), a smaller dose of 2.5 mg (1/2 tablets of 5 mg) should be given. In the case of a decrease in blood pressure (systolic blood pressure is less than or equal to 100 mm Hg), a daily dose of 5 mg can be administered if it is necessary to temporarily reduce to 2.5 mg (1/2 tablets 5 mg each). In the case of a long pronounced decrease in blood pressure (systolic blood pressure below 90 mm Hg for more than 1 hour), treatment with Liten® should be stopped.
Diabetic Nephropathy
In patients with type 2 diabetes mellitus, 10 mg of Liten® is administered once a day. The dose may, if necessary, be increased to 20 mg once a day in order to achieve diastolic blood pressure values below 75 mmHg. in the "sitting" position. In patients with type 1 diabetes, the dose is the same, in order to achieve diastolic blood pressure values below 90 mm Hg. in the "sitting" position.

Side effects:The frequency of occurrence of side effects is characterized as often (> 1%), rarely (<1%).The most common side effects; dizziness, headache, fatigue, diarrhea, dry cough, nausea.
From the central nervous system: often - paresthesia, lability of mood, confusion, drowsiness, convulsive twitching of the muscles of the extremities and lips, rarely asthenic syndrome.
From the hematopoiesis: rarely - leukopenia, neutropenia, agranulocytosis, thrombocytopenia, with long-term treatment - anemia (reduction of hemoglobin, hematocrit, erythropenia).
Laboratory indicators: often - hyperkalemia, hyponatremia; rarely - hyperbilirubinemia, increased activity of "hepatic" transaminases, hypercreatininaemia, increased concentrations of urea and creatinine.
From the cardiovascular system: often - marked decrease in blood pressure, orthostatic hypotension; rarely - chest pain, tachycardia, bradycardia, aggravation of symptoms of chronic heart failure, violation of atrioventricular conduction, myocardial infarction.
From the digestive system: rarely - dryness of the oral mucosa, anorexia, dyspepsia, taste disorders, abdominal pain, pancreatitis, jaundice (hepatocellular or cholestatic), hepatitis.
From the genitourinary system: rarely - a violation of kidney function, oliguria, anuria, acute renal failure, uremia, proteinuria, decreased potency.
From the respiratory system: rarely shortness of breath, bronchospasm.
From the skin: rarely - urticaria, pruritus, increased sweating, alopecia, photosensitivity.
Allergic reactions: rarely angioedema, swelling of the face, limbs, lips, tongue, epiglottis and / or larynx, skin rashes, itchy skin, fever, false positive antinuclear antibody test results, increased erythrocyte sedimentation rate (ESR), eosinophilia, leukocytosis. In rare cases, there is an intestinal angioedema.
Other: rarely - arthralgia, arthritis, vasculitis, myalgia.

Overdose:Symptoms (occur when taking a single dose of 50 mg): a marked decrease in blood pressure; dryness of the oral mucosa, drowsiness, urinary retention, constipation, anxiety, increased irritability.
Treatment: a specific antidote is absent; symptomatic therapy. Gastric lavage, application of enterosorbents and laxatives. Intravenous introduction of 0.9% sodium chloride solution was shown.In the case of a sustained bradycardia, the use of an artificial pacemaker is necessary. It is necessary to monitor blood pressure, indicators of water-electrolyte balance. Hemodialysis is effective.

Interaction:With the simultaneous use of the drug with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium, cyclosporine, increases the risk of hyperkalemia, especially with impaired renal function, so they can be used together only with regular monitoring of potassium ions in the blood serum and kidney function.
The simultaneous use of lisinopril with beta-blockers, slow calcium channel blockers (BCCC), diuretics, tricyclic antidepressants / neuroleptics and other antihypertensive drugs increases the severity of antihypertensive action.
Lizinopril slows down the excretion of lithium preparations. Therefore, with simultaneous use, it is necessary to regularly monitor the concentration of lithium in the blood serum. Antacids and colestramine reduce the absorption of lisinopril in the gastrointestinal tract.
When combined with insulin and hypoglycemic agents for oral administration, there is a risk of developing hypoglycemia.
Non-steroidal anti-inflammatory drugs (NSAIDs) (including selective inhibitors of cyclooxygenase-2 (COX-2)), estrogens, adrenomimetics reduce the antihypertensive effect of lisinopril.
With simultaneous use of ACE inhibitors and preparations of gold intravenously (sodium aurotomy malate) describes a symptom complex, which includes facial flushing, nausea, vomiting and lowering blood pressure.
When combined with selective serotonin reuptake inhibitors, it can lead to severe hyponatraemia.
Simultaneous use with allopurinol, procainamide, cytostatics can lead to leukopenia.

Special instructions:Symptomatic arterial hypotension
Most often, a marked decrease in blood pressure occurs with a decrease in the volume of circulating blood caused by diuretic therapy, reduction of table salt in food, dialysis, diarrhea, or vomiting. In patients with chronic heart failure with simultaneous renal insufficiency or without it, a marked decrease in blood pressure is possible.It is more often detected in patients with severe chronic heart failure, as a result of the use of large doses of diuretics, hyponatremia or impaired renal function. In such patients, treatment with Liten® should be started under the strict supervision of a doctor (with care to select the dose of the drug and diuretics).
With acute myocardial infarction
The use of standard therapy (thrombolytics, acetylsalicylic acid as an antiaggregant agent, beta-blockers). Liten® can be used in conjunction with intravenous administration or with the use of therapeutic transdermal systems of nitroglycerin.
Similar rules should be adhered to when assigning patients with coronary heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.
Transient hypotensive reaction is not a contraindication for taking the next dose of the drug.
When Liten® is used, in some patients with chronic heart failure, but with normal or reduced blood pressure, a decrease in blood pressure may be noted, which is usually not the reason for discontinuing treatment.
Before starting treatment with Liten®, if possible, normalize the sodium content and / or replenish the lost volume of fluid, carefully monitor the effect of the initial dose of Liten® on the patient.
In the case of stenosis of the renal artery (in particular, with bilateral stenosis, or in the presence of stenosis of the artery of a single kidney), as well as inadequate circulation due to lack of sodium and / or liquid, Liten® can lead to impaired renal function, acute renal failure , which is usually irreversible after drug withdrawal. Surgery / general anesthesia
With extensive surgical interventions, as well as with the use of other drugs that cause a decrease in blood pressure, lisinopril, blocking the formation of angiotensin II, can cause a pronounced unpredictable decrease in blood pressure.
In elderly patients, the same dose leads to a higher concentration of the drug in the blood, therefore special caution is required when determining the dose. Because the potential risk of agranulocytosis can not be ruled out, periodic monitoring of the blood picture is required.When the drug is used in dialysis with a polyacryl-nitrile membrane, anaphylactic shock can occur, so it is recommended that either a different type of membrane for dialysis or the appointment of other antihypertensive agents.

Effect on the ability to drive transp. cf. and fur:There is no data on the effect of Liten® on the ability to drive vehicles and mechanisms, applied in therapeutic doses, but it must be borne in mind that at the beginning of treatment it is possible to develop arterial hypotension, which can affect the ability to drive vehicles and work with potentially dangerous mechanisms, and there may be dizziness and drowsiness, so be careful.

Form release / dosage:Tablets of 5, 10, 20 mg.

Packaging:Tablets of 5 mg.
For 10 or 20 tablets in a blister of PVC / A1 - foil. By 1, or 2, or 5, or 10 blisters with instructions for use in a cardboard pack.
Tablets of 10 mg and 20 mg.
For 10 tablets in a blister of PVC / A1 - foil. By 1, or 2, or 3, or 10 blisters with instructions for use in a cardboard bundle.

Storage conditions:Store at a temperature of no higher than 25 ° C, in a place protected from light.
Keep out of the reach of children.

Shelf life:3 years.
Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-000549

Date of registration:23.07.2010

Expiration Date:Unlimited

The owner of the registration certificate:Boznalek, AOBoznalek, AO Bosnia and Herzegovina

Manufacturer: & nbsp

BOSNALIJEK, d.d. Bosnia and Herzegovina

Representation: & nbspBOSNALEK AO BOSNALEK AO Bosnia and Herzegovina

Information update date: & nbsp2016-11-18

Illustrated instructions

Instructions

Liten® (Liten)