LIZIGAMMA

Active material: Lisinopril
When ATH: C09AA03
CCF: ACE inhibitor
ICD-10 codes (testimony): I10, I21, I50.0, N08.3
When CSF: 01.04.01.02
Manufacturer: WÖRWAG PHARMA GmbH & Co. KG (Germany)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills white, round, beveled inside edges, scored on one side and marking “5” – another.

Excipients: mannyt, phosphate calcium phosphate dihydrate, corn starch, pre-gelatinized starch, colloidal silicon dioxide, magnesium stearate.

10 PC. – blisters (3) – packs cardboard.

Pills white, round, lenticular, scored on one side and marking “10” – another.

Excipients: mannyt, phosphate calcium phosphate dihydrate, corn starch, pre-gelatinized starch, colloidal silicon dioxide, magnesium stearate.

10 PC. – blisters (3) – packs cardboard.

Pills white, round, lenticular, scored on one side and marking “20” – another.

Excipients: mannyt, calcium hydrogen phosphate dihydrate, corn starch, pre-gelatinized starch, colloidal silicon dioxide, magnesium stearate.

10 PC. – blisters (3) – packs cardboard.

Pharmacological action

Antihypertensive drugs, ACE inhibitor. Reduces the formation of angiotensin II from angiotensin I , that leads to direct reduction of aldosterone allocation. It reduces the degradation of bradykinin, and increases the synthesis of prostaglandins. Reduces PR, FROM, preload, the pressure in the pulmonary capillaries, It causes an increase in cardiac output and increase tolerance to myocardial stress in patients with chronic heart failure. It expands the artery to a greater extent, than veins. Some effects are explained by the influence on the tissue renin-angiotensin system. Prolonged use reduces myocardial hypertrophy and arterial walls resistive type. It improves blood flow to ischemic myocardium.

ACE inhibitors prolong survival in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients, myocardial infarction without clinical manifestations.

Pharmacokinetics

Absorption

After oral administration about 25% lisinopril is absorbed from the gastrointestinal tract. Eating does not affect the absorption. Absorption averages 30%, bioavailability – 29%. C_max plasma (90 ng / ml) achieved through 7 no.

Distribution

Lisinopril is almost not associated with blood plasma proteins. The permeability of the BBB and placental barrier is low.

Metabolism

Lisinopril is not biotransformed in the body.

Deduction

Excreted by the kidneys in unchanged form. T_1/2 is 12 no.

Pharmacokinetics of individual patient groups

In patients with chronic heart failure lysinoprile clearance reduced absorption and.

In patients with renal failure lysinoprile concentration several times prevyšaet concentration in the blood plasma from volunteers, with increasing time (C)_max in plasma and increase T_1/2.

In elderly patients the drug concentration in the blood plasma and AUC 2 times, than in patients of young age.

Testimony

- Arterial hypertension (as monotherapy or in combination with other antihypertensives);

- Congestive heart failure (in a combination therapy for the treatment of patients, receiving cardiac glycosides and/or diuretics);

- Early treatment of acute myocardial infarction (first 24 h with stable hemodynamics indices to maintain these indicators and prevent left ventricular dysfunction and heart failure);

- Diabeticheskaya nephropathy (to reduce proteinuria in patients with diabetes insulinzawisimam normal ad and non-insulin dependent diabetes mellitus patients with arterial hypertension).

Dosage regimen

The drug is taken orally, regardless of the meal.

Arterial hypertension

In hypertension patients, not receiving other antihypertensive, appoint 5 mg 1 time / day. In the absence of effective dose increase every 2-3 of the day on 5 mg-medium therapeutic dose 20-40 mg / day (increase the dose over 40 mg/day is not typically leads to a further reduction of HELL). The usual daily maintenance dose – 20 mg. The maximum daily dose – 40 mg.

Full effect is usually through 2-4 weeks of treatment, What to consider when increasing the dose. With insufficient clinical effect of the drug can be combined with other antihypertensive agents.

If the patient has received prior treatment with diuretics, the use of these drugs should be discontinued for 2-3 the day before the application Lizigammy^®. If this is not possible, the initial dose Lizigammy^® should not exceed 5 mg / day. In this case, after the first dose recommended medical supervision for a few hours (maximum effect is achieved after about 6 no), t. to. It may be marked reduction of blood pressure.

If renovascular hypertension or other conditions with increased activity of the Renin-angiotensin-aldosterone system activity also designate product in the low dose- 2.5-5 mg / day, under advanced medical supervision (BP control, renal function, potassium concentration in blood serum). Supporting dose under strict medical supervision should be set depending on the dynamics of HELL.

In renal insufficiency since, What lisinopril displayed kidneys, the starting dose set depending on QC. Then, in line with the reaction should establish dose under conditions of frequent monitoring of renal function, potassium level, sodium in the serum.

When resistant hypertension the drug is prescribed in a dose 10-15 mg / day for a long time.

In chronic heart failure treatment is initiated with dosages 2.5 mg 1 times per day with a consequent increase in the dose 2.5 mg after 3-5 days before the regular maintenance 5-20 mg / day. The maximum dose – 20 mg/day.

Elderly patients often observed a stronger long-term gipotenzivne effect, that is connected with the decrease of speed breeding lisinopril (It is recommended to begin treatment with 2.5 mg / day).

In acute myocardial infarct (in a combination therapy) on the first day of drug appointed dose of 5 mg, then 5 mg a day, 10 mg in two days and then 10 mg 1 time / day. In patients with acute myocardial infarction, the drug should be used not less than 6 weeks.

At the start of treatment or during the first 3 days after acute myocardial infarction in patients with low systolic HELL (120 mmHg. or below) the agent should be appointed to a lesser dose- 2.5 mg. In the case of BP reduction (systolic blood pressure less than or equal 100 mmHg.) daily dose 5 mg can be, if necessary, temporarily reduced to 2.5 mg. In case of prolonged significant decrease in blood pressure (systolic blood pressure less than 90 mmHg. more 1 no), treatment with Lizigamma^® discontinue.

In diabetic nephropathy in patients with insulinzawisimam diabetes drug appointed dose of 10 mg 1 time / day. Dose can be, if necessary, increased to 20 mg 1 time / day to achieve diastolic BP values ​​below 75 mmHg. in the sitting position. In patients with non-insulin-dependent diabetes mellitus dose is the same, with a view to achieving values diastolic HELL below 90 mmHg. in the sitting position.

Side effect

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

Side effects with a frequency <1%

Cardio-vascular system: marked reduction in blood pressure, orthostatic hypotension, heart rhythm disturbances, palpitations, tachycardia, myocardial infarction, cerebrovascular stroke in patients at risk of disease, due to the significant decrease in blood pressure.

CNS: fatigue, drowsiness, jerking of the limbs and lips, asthenic syndrome, mood lability, confusion, reduced potency.

From the hematopoietic system: possible leukopenia, neutropenia, agranulocytosis, thrombocytopenia, long-term treatment – a slight decrease in hemoglobin concentration and hematocrit, erythropenia.

On the part of the digestive tract: dry mouth, anorexia, dyspepsia, changes in taste, stomach ache, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

From the urinary system: impairment of renal function, oligurija, anurija, acute renal failure, uremia, proteinuria.

Dermatological reactions: hives, increased perspiration, itching, alopecia.

Allergic reactions: 0.1% – angioedema (face, lips, language, larynx, or epiglottis, upper and lower limbs).

Laboratory findings: hyperkalemia, azotemia, hyperuricemia, giperʙiliruʙinemija, increase in liver enzymes, particularly those with a history of renal disease, diabetes and hypertension, renovascular.

Other: myalgia, fever, impaired fetal growth; syndrome, including acceleration of ESR, arthralgia and appearance of anti-nuclear antibodies.

Contraindications

- A history of angioedema, incl. as a result of the application of ACE inhibitors;

- Hereditary angioedema;

- Up to 18 years (efficacy and safety have not been established);

- Hypersensitivity to the drug;

- Hypersensitivity to other ACE inhibitors.

FROM caution the drug should be used in patients with acute violations of the kidney, bilateral renal artery stenosis or stenosis of the artery only kidneys with progressive azotemia, in condition after kidney transplant, renal failure, azotemia, hyperkalemia, the mouth of aortic stenosis, with hypertrophic obstructive kardiomipatiej, primary giperal′dosteronizmom, with arterial gipotenziei, cerebrovascular diseases (incl. when cerebrovascular insufficiency), with CORONARY HEART DISEASE, coronary insufficiency, Autoimmune systemic diseases of connective tissue (incl. scleroderma, SLE); oppression kostnomozgovy blood; Background on sodium restricted diets; in gipovolemičeskih conditions (incl. due to diarrhea, vomiting); in elderly patients.

Pregnancy and lactation

The use of lisinopril in pregnancy is contraindicated. When establishing pregnancy taking drugs Lizigamma^® should be discontinued as soon as possible.

Reception of ACE inhibitors in groups II and III trimester of pregnancy has adverse effects on the fetus (may be marked reduction of blood pressure, renal failure, hyperkalemia, skull hypoplasia, intrauterine fetal death).

Lisinopril crosses the placental barrier. Data on the adverse effects of drug Lizigamma^® on the fetus in case of use in the first trimester of pregnancy are not available. For newborns and babies, who underwent in utero effects of ACE inhibitors, should be closely monitored for early detection of significant decrease in blood pressure, oligurii, hyperkalemia.

There are no data on the penetration of lisinopril in breast milk. For the period of treatment it is necessary to cancel the breast-feeding.

Cautions

The most commonly expressed lower ad occurs when the body's gipogidratacii, caused by diuretic therapy, reduction of salt in food, dializom, diarrhea or vomiting. In patients with chronic heart failure and accompanying renal insufficiency or without it, perhaps marked reduction of blood pressure. Symptomatic hypotension more often detected in patients with severe stage of chronic heart failure, as a consequence of the use of diuretics at higher doses, hyponatremia or impaired renal function. Treatment of such patients Lizigammoj^® should begin under strict medical supervision and with caution to carry out selection of dosage and diuretics.

Patients, suffering from ISCHEMIC HEART DISEASE, cerebrovascular insufficiency, the sharp decline ad can lead to myocardial infarction or stroke, Therefore, treatment Lizigammoj^® You should also start under strict medical supervision and with caution to carry out selection of dosage and diuretics.

Transient hypotensive response is not a contraindication to receiving the next dose.

When applying Lizigammy^® some patients with chronic heart failure, but with normal or low blood pressure, there may be a decrease in blood pressure, which is usually not a cause for discontinuation of treatment.

Prior to the start of treatment Lizigammoj^®, possibly, sodium concentration should be normalized and / or fill the volume of fluid lost, carefully monitor the effect of the initial reaction to the patient dose Lizigammy^®.

In the case of stenosis of the renal artery (especially when bilateral stenosis, or if there is stenosis of artery only kidneys), and circulatory failure due to lack of sodium and / or liquid, use Lizigammy^® can lead to the violation of the kidney, Acute renal failure, which is usually irreversible after drug withdrawal.

In acute myocardial infarction shows the use of standard therapy (thrombolytics, acetylsalicylic acid, beta-blockers). Lizigammu^® can be used together with the/in the introduction or use of therapeutic transdermal nitroglycerin systems.

With extensive surgery, as well as the application of other medicaments, causing a decrease in blood pressure, Lisinopril, blocking the formation of angiotensin II , can cause unpredictable pronounced reduction in blood pressure.

In elderly patients when use of the drug in the same dose as in younger patients, there is a higher concentration of lisinopril in plasma, Therefore, when determining the dose required special care.

Since we can not exclude the potential risk of agranulocytosis, requires periodic monitoring of blood picture. In applying the drug in a dialysis membrane of polyacrylonitrile may occur anaphylactic shock, it is recommended that a different type of dialysis membrane, or administration of other antihypertensive drugs.

Effects on ability to drive and use machines

No data on the effects of lisinopril in therapeutic doses on the ability to manage vehicles and mechanisms, However, it should be taken into account, that in applying the drug may experience dizziness. Therefore, patients, receiving the drug Lizigamma^®, should use caution when performing work, require high concentration and speed of psychomotor reactions.

Overdose

Symptoms (arise when administered a single dose 50 mg): marked reduction in blood pressure; dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability.

Treatment: simptomaticheskaya therapy, in / in a liquid, controlling HELL, vodno-elektrolitnogo balance and normalize last.

Lisinopril can be removed from the body using hemodialysis.

Drug Interactions

While applying the drug with kalisberegatmi dioretikami (spironolactone, triamterene, amilorid), potassium, Deputy salt, containing potassium, increased risk of hyperkalemia, especially in patients with impaired renal function (data combinations should be administered with extreme caution, only on the basis of individual decisions of the physician under regular supervision of the content of potassium in the blood serum and kidney function).

When supplemental diuretic effectively delivered to patients, receiving lisinopril, usually, develops additive antihypertensive effect – the risk of significant decrease in blood pressure (this combination should be used with caution). Lisinopril reduces withdrawal potassium from the body in the treatment dioretikami.

Together with other antigipertenzivei means develops additive effect (this combination should be used with caution).

In an application with NSAIDs (incl. with indomethacin), Estrogen, as well as the adrainostimulatorami decreases the antihypertensive lisinopril (data combination should be used with caution).

Together with the use of lithium may reduce the excretion of lithium (this combination should be used with caution, requires regular monitoring of serum lithium concentrations).

While admission antacids and kolestiramin reduce suction lisinopril from the intestine (data combination should be used with caution).

Ethanol enhances the effect of the drug.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in a dry, protected from light, inaccessible to children at temperature not exceeding 25 ° C. Shelf life – 3 year.