Lizinopril NL-Krka - instructions for use, dose, side effects, contraindications

Active substanceHydrochlorothiazide + LysinoprilHydrochlorothiazide + Lysinopril

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Dosage form: & nbspPills.

Composition:

1 tablet contains:

Active substances:

Lysinopril dihydrate 10.89 mg

(which corresponds to lisinopril 10.00 mg)

Hydrochlorothiazide 12.5 mg

Excipients:

Mannitol 18.70 mg

Calcium hydrogen phosphate dihydrate 57.14 mg

Corn starch

pregelatinized 4.00 mg

Croscarmellose sodium 4.40 mg

- Dye 1.60 mg

Magnesium stearate 0.77 mg

- Dye:

Pregelatinized starch 1,488 mg

Dye iron iron oxide yellow (E 172) 0.080 mg

The iron dye red oxide (E 172) 0.032 mg

Description:Round biconvex tablets are light orange with a reddish shade of color with impregnations of a darker color, on one side are engraved with the letters "LH".

Pharmacotherapeutic group:hypotensive combined agent (angiotensin-converting enzyme inhibitor + diuretic).

ATX: & nbsp

C.09.B.A.03 Lizinopril in combination with diuretics

Pharmacodynamics:

A drug Lisinopril NL-KRKA is a combination of fixed doses of lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide (a thiazide diuretic), which have a complementary effect and complement each other's antihypertensive effect.

Lisinopril

The ACE inhibitor reduces the formation of angiotensin II from angiotensin I. Reducing 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 (OPSS), arterial pressure (BP), preload on the myocardium, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and increased tolerance to exercise in patients with chronic heart failure (CHF). Expands arteries more than veins. Some effects are explained by the effect on the renin-angiotensin-aldosterone system (RAAS).With prolonged use, the severity of myocardial hypertrophy and the walls of arteries of resistive type decreases. Improves the blood supply of the ischemic myocardium.

ACE inhibitors increase life expectancy in patients with CHF, slow the progression of left ventricular dysfunction in patients who underwent myocardial infarction without clinical manifestations of heart failure. The antihypertensive effect begins in about 6 hours and persists for 24 hours. The duration of the effect also depends on the amount of the dose. The onset of action is after 1 hour. The maximum effect is 6-7 hours. With arterial hypertension, the effect is observed in the first days after the start of treatment, stable effect develops after 1 -2 months.

With a sharp withdrawal of lisinopril, there is no pronounced increase in blood pressure.

In addition to reducing blood pressure lisinopril reduces albuminuria. In patients with hyperglycemia contributes to the normalization of the function of the damaged glomerular endothelium.

Hydrochlorothiazide

A thiazide diuretic whose diuretic effect is associated with a disruption of the reabsorption of sodium, chlorine, potassium, magnesium, water in the distal nephron; delays the excretion of calcium ions, uric acid.Has antihypertensive properties; antihypertensive effect develops due to the expansion of arterioles. Virtually no effect on normal blood pressure.

The diuretic effect develops in 1-2 hours, reaches a maximum after 4 hours and persists for 6-12 hours. Antihypertensive effect occurs in 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.

Lysinopril and hydrochlorothiazide, with simultaneous use, have an additive antihypertensive effect.

Pharmacokinetics:

Simultaneous use of lisinopril and hydrochlorothiazide does not affect the bioavailability and pharmacokinetics of each of the active components of the drug.

Lisinopril

After taking lisinopril, the maximum concentration in the blood serum is reached after 7 hours. It weakly binds to blood plasma proteins. The average degree of absorption of lisinopril is about 25%, with a significant interindividual variability (6-60%). Food does not affect the absorption of lisinopril. Lisinopril does not undergo metabolism and is excreted unchanged only by the kidneys.After repeated use, the half-life (T1 / 2) of lisinopril is 12 hours. Impaired renal function slows the excretion of lisinopril, but this slowing becomes clinically significant only when the glomerular filtration rate decreases below 30 mL / min. In elderly patients, the mean maximum concentration of lisinopril in plasma and AUC (the area under the concentration-time curve), on average, is 2 times higher than in younger patients. Lisinopril is excreted from the body by hemodialysis. It penetrates to a small extent through the blood-brain barrier.

Hydrochlorothiazide

It is not metabolized, but is rapidly eliminated through the kidneys. T1 / 2 hydrochlorothiazide ranges from 5.6 to 14.8 hours. At least 61% of the ingested hydrochlorothiazide is excreted unchanged for 24 hours. Hydrochlorothiazide penetrates the placental barrier, but does not penetrate the blood-brain barrier.

Indications:- Arterial hypertension (in patients who are shown combined therapy).

Contraindications:Hypersensitivity to active substances or any other components of the drug (incl.to other ACE inhibitors and sulfonamide derivatives); anuria, angioedema (including anamnesis from the use of ACE inhibitors); hemodialysis using high-flow membranes, hypercalcemia, porphyria, precoma, hepatic coma, expressed CRF (creatinine clearance less than 30 ml / min), exacerbation of gout, diabetes mellitus (severe forms), pregnancy, breastfeeding period, hereditary angioedema and idiopathic angioedema, age under 18 years (efficacy and safety not established).

Carefully:Aortic and / or mitral stenosis, hypertrophic obstructive cardiomyopathy, bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney with progressive azotemia, condition after kidney transplantation, moderate chronic renal failure (QC more than 30 ml / min), primary hyperaldosteronism, arterial hypotension , bone marrow hypoplasia, hyponatremia (an increased risk of developing hypotension in patients on a low-salt or salt-free diet), conditions accompanied by lowering the BCC (incl.diarrhea, vomiting), connective tissue diseases (SLE, scleroderma), diabetes mellitus, gout, hyperuricemia, hyperkalemia, hepatic insufficiency, cerebrovascular insufficiency, severe chronic heart failure, advanced age, hemodialysis.

Pregnancy and lactation:

Pregnancy

Application of the drug Lisinopril NL-KRKA during pregnancy is contraindicated. ACE inhibitors in the II and III trimesters of pregnancy have an adverse effect on the fetus (marked decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, fetal death). For newborns and infants who have undergone intrauterine exposure to ACE inhibitors, it is recommended to monitor for the timely detection of a marked decrease in blood pressure, oliguria, and hyperkalemia. The use of hydrochlorothiazide is contraindicated in the first trimester of pregnancy.

In the case of planning or diagnosing the onset of pregnancy, the drug Lisinopril NL-KRKA should be stopped immediately.

Breast-feeding

If it is necessary to use the drug Lisinopril NL-KRKA during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, 1 tablet of the drug Lisinopril NL-KRKA once a day.

If necessary, the daily dose can be increased to 2 tablets (possibly the use of drugs Lisinopril NL 20-KRKA or Lisinopril ND-KRKA in other dosages). Symptomatic arterial hypotension can occur after taking the initial dose of the drug. Such cases are more common in patients with reduced circulating blood volume (BCC) and reduced electrolyte content due to previous treatment with diuretics. Therefore, you should stop taking diuretics 2-3 days before the start of treatment with the drug Lisinopril NL-KRKA.

Renal impairment

A drug Lisinopril NL-KRKA is contraindicated in cases of severe renal dysfunction (KC 30 ml / min or less).

With QC 30-80 ml / min, the use of the drug Lisinopril NL-KRKA, it is possible only after selecting the dose of each of the active components of the preparation separately.

Elderly patients: correction of the dose is not required.

Side effects:

Classification of the incidence of adverse events (WHO):

very often> 1/10

often from> 1/100 to <1/10

infrequently from> 1/1000 to <1/100

rarely from> 1/10000 to <1/1000

very rarely from <1/10000, including individual messages.

In each group, unwanted effects are presented in order of decreasing severity.

From the digestive system:

rarely: dryness of the oral mucosa, nausea, vomiting, diarrhea, constipation, pancreatitis;

very rarely: intestinal edema of the intestine, abdominal pain, anorexia, gastritis, hepatitis, hepatic insufficiency, cholestatic jaundice;

From the cardiovascular system:

often: marked reduction in blood pressure (including orthostatic hypotension), chest pain;

rarely: tachycardia, bradycardia, aggravation of symptoms of the course of chronic heart failure, violation of atrioventricular (AV) conduction, myocardial infarction or impaired cerebral circulation due to excessive arterial hypotension;

From the nervous system: often: dizziness, headache;

infrequent: lability of mood, impaired concentration, increased fatigue, drowsiness, sleep disturbance, convulsive twitching of the muscles of the extremities and lips;

rarely: paresthesia, asthenic syndrome, confusion, depression;

From the respiratory system; often: a "dry" cough;

rarely: bronchospasm, rhinitis, sinusitis, dyspnea, apnea, allergic alveolitis / eosinophilic pneumonia;

From the genitourinary system: rarely: decreased potency;

very rarely: uremia, oliguria / anuria, glucosuria, renal dysfunction, acute renal failure, interstitial nephritis:

From the skin:

infrequently: skin rash, photosensitivity, alopecia, itching, urticaria; very rarely: increased sweating, pemphigus, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, vasculitis, psoriasis;

From the immune system:

very rarely: angioedema, swelling of the face, lips, tongue, throat and / or larynx, limbs, hypersensitivity reactions *;

From the musculoskeletal system: rarely: muscle weakness, arthralgia / arthritis;

From the sense organs:

very rarely: transient disturbance of visual acuity, photophobia, xantopsy;

From the hemopoietic organs: neutropenia / agranulocytosis, leukopenia, thrombocytopenia, oppression of bone marrow hematopoiesis.

Other:

rarely: general weakness, asthenia, Raynaud's syndrome, gynecomastia, exacerbation of gout, impaired fetal kidney development, hypoglycemia; very rarely: sialadenitis;

Laboratory indicators:

rarely: hyperglycemia, hyperuricemia and hyperkalemia or hypokalemia, increased urea and creatinine concentrations, decreased hematocrit and hemoglobin, increased activity of "hepatic" enzymes and / or bilirubin, hypercholesterolemia, hypertriglyceridemia;

very rarely: hyponatremia, hypomagnesemia, hypochloraemia, hypercalcemia, hemolytic anemia, aplastic anemia.

* There are reports of a simtomocomplex, which may include fever, vasculitis, myalgia. arthralgia / arthritis, positive antinuclear antibodies, increased ESR, eosinophilia, leukocytosis.

Overdose:

In case of an overdose with the combination of lisinopril / hydrochlorothiazide, the following symptoms are possible: marked decrease in blood pressure, collapse, tachycardia, rapid breathing, sensation of sertsebieniya, bradycardia, cough, dizziness, dryness of the oral mucosa, urinary retention, constipation, anxiety, water-electrolyte balance disturbance, renal insufficiency.

Treatment: gastric lavage and / or the appointment of activated carbon, restoration of water-electrolyte balance in a hospital. With a pronounced decrease in blood pressure, it is necessary to transfer the patient to the "lying" position on the back with the legs raised upwards; further measures should be taken to increase bcc (introduction of 0.9% sodium chloride solution intravenously). If necessary, the use of angiotensin II, with bradycardia - atropine or the setting of an artificial pacemaker. It is necessary to control diuresis, urea concentration, creatinine and electrolytes in blood serum. Hemodialysis is effective.

Interaction:

With the simultaneous use of lisinopril and hydrochlorothiazide with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations, potassium-containing substitutes for table salt increase the risk of hyperkalemia, especially in patients with chronic renal failure. Hypoglycemic agents for oral administration (derivatives of sulfonylureas) and insulin: the use of ACE inhibitors can increase the hypoglycemic effect hypoglycemic agents for ingestion and insulin in patients with diabetes mellitus; when they are used simultaneously, there may be an increase in glucose tolerance, which may require correction of doses of hypoglycemic agents for ingestion and insulin.

Simultaneous application with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants increases the hypotensive effect. Non-steroidal anti-inflammatory drugs (indomethacin and others), estrogens reduce the antihypertensive effect of lisinopril.

Simultaneous use of lisinopril and hydrochlorothiazide with lithium preparations leads to a slowing down of lithium excretion and an intensification of the cardiotoxic and neurotoxic effect of lithium.

Antipsychotic drugs (antipsychotics) can enhance the hypotensive effect of lisinopril.

Simultaneous application with antacids, colestyramine or colestipol leads to a decrease in the absorption of lisinopril and hydrochlorothiazide in the gastrointestinal tract.

Preparations of gold: with the use of ACE inhibitors, including lisinopril in patients receiving gold preparations (sodium aurothiomalate), nitrate-like reactions (nausea, vomiting, marked decrease in blood pressure, hyperemia of the facial skin) were noted.

Allopurinol, cytostatics, immunosuppressants, glucocorticosteroids (for systemic use) and procainamide: simultaneous use of these drugs with ACE inhibitors may increase the risk of developing leukopenia.

Simultaneous application with glucocorticosteroids, adrenocorticotropin, carbenoxolone, amphotericin B can increase the balance of electrolytes, especially potassium.

Simultaneous application with lovastatin increases the risk of hyperkalemia. Cyclosporin increases the risk of renal dysfunction and the development of hyperkalemia. When used simultaneously with sotalol the risk of arrhythmia increases. Because of the risk of developing hypokalemia, caution should be exercised when using hydrochlorothiazide and tachycardia-inducing pirouettes, for example, some antipsychotic and other means.

Means for general anesthesia: ACE inhibitors can enhance the antihypertensive effect of certain agents for general anesthesia.

Sympathomimetics can weaken the antihypertensive action of lisinopril.

Diuretics (thiazide and "loop"): the use of diuretics in high doses can lead to hypovolemia (due to a decrease in the volume of circulating blood), and the addition of lisinopril to a pronounced decrease in blood pressure.

Combination of lisinopril and hydrochlorothiazide weakens the effect of hypoglycemic agents for oral administration, norepinephrine, epinephrine and antidotal drugs, increases the effects (including side effects) of cardiac glycosides, the effect of peripheral muscle relaxants, reduces the excretion of quinidine. Lysinopril and hydrochlorothiazide reduces the effect of oral contraceptives. Ethanol enhances the hypotensive effect of lisinopril and hydrochlorothiazide. With simultaneous use with methyldopa, the risk of hemolysis increases.

Special instructions:

Symptomatic arterial hypotension

Most often, a marked decrease in blood pressure occurs with a decrease in bcc caused by diuretic therapy, a decrease in the amount of salt in the diet, dialysis, diarrhea, or vomiting.

With cirrhosis of the liver accompanied by edema and ascites, arterial hypotension, CHF, there may be a significant activation of RAAS, especially with pronounced hypovolemia and a decrease in the electrolyte content in the blood plasma (against a background of a salt-free diet or a long-term intake of diuretics).

The use of an ACE inhibitor causes blockade of the RAAS, in connection with this, a sharp decrease in blood pressure and / or an increase in the concentration of creatinine in the blood plasma, indicating the development of acute renal failure, which is often possible with the initial application of the drug Lisinopril NL-KRKA or during the first two weeks of therapy.

Thus, in patients with a decrease in fluid volume against diuretic therapy, dialysis, diarrhea, and vomiting, treatment should be started under the strict supervision of a physician, with care to conduct a dose of the drug.

Renal impairment

Thiazide diuretics should not be used in patients with impaired renal function; they are ineffective with QC 30 ml / min or less (ie, with moderate or severe renal impairment).

Lysinopril NL-KRKA preparation can not be used in patients with renal insufficiency (CC less than 80 ml / min) until the doses of each of the components individually corresponding to the doses in the combined preparation are selected.

If patients with hypertension without obvious signs of existing kidney disease have an increase in the concentration of urea and creatinine in the blood serum on the background of the drug Lisinopril NL-KRKA, further application should be discontinued.Renewal of therapy is possible either by lower doses or by monotherapy of the active components of the drug.

In patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney taking ACE inhibitors, an increase in the concentration of urea and serum creatinine, usually reversible after the abolition of therapy, is possible. Dysfunction of the liver

Thiazide diuretics must be used with caution in patients with impaired liver function or with progressive liver damage, since in such patients even minimal changes in electrolyte balance can trigger the development of the hepatic coma. The use of ACE inhibitors in patients with liver disease can lead to the development of fulminant liver necrosis.

Patients with diabetes mellitus and other endocrine pathologies

When using the drug Lisinopril NL-KRKA patients with diabetes mellitus receiving hypoglycemic agents for ingestion or insulin during the first month of therapy should regularly monitor the concentration of glucose in the blood. Thiazide diuretics can reduce the excretion of calcium by the kidneys and cause a temporary moderate increase in serum calcium.Expressed hypercalcemia may be a manifestation of diagnosed hyperparathyroidism. Before the study of the function of parathyroid glands, thiazide diuretics should be discontinued.

Against the background of therapy with thiazide diuretics, the concentration of cholesterol and triglycerides can increase.

In some patients, therapy with thiazide diuretics can exacerbate hyperuricemia and / or aggravate the course of gout. But, lisinopril enhances the excretion of uric acid by the kidneys, thereby counteracting the hyperuricemic effect of hydrochlorothiazide.

During the treatment period, regular monitoring of calcium, potassium, glucose, urea, lipids and creatinine in the blood plasma is necessary.

Hypersensitivity / angioedema (angioedema)

With the use of ACE inhibitors, including lisinopril, in rare cases development of angioedema, lip, tongue, pharynx and / or larynx can be observed.

If these symptoms appear, the drug should be discontinued immediately, the patient should be observed until the signs of edema disappear completely.

If angioedema affects only the face and lips, then its manifestations usually go away alone or antihistamines may be used to treat its symptoms. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.

When such symptoms occur, immediately enter subcutaneously epinephrine (adrenaline) (at 1: 1000 dilution (0.3 or 0.5 mL) and / or provide airway patency.

Patients with a history of Quincke edema who are not associated with the administration of ACE inhibitors may be at increased risk of developing it with the use of drugs of this group.

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. In this case, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without a previous angioedema and at a normal level of C-1 - esterase. The diagnosis is established by means of computed tomography of the abdominal cavity, ultrasound examination or at the time of surgical intervention.Symptoms disappear after the cessation of the use of ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the differential diagnosis should take into account the possibility of developing angioedema of the intestine.

Anaphylactoid reactions during desensitization procedures

There are separate reports on the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the poison of Hymenoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The appointment of an ACE inhibitor should be avoided for patients receiving immunotherapy with venom of Hymenoptera. Nevertheless, the development of anaphylactoid reactions can be avoided by the temporary withdrawal of the ACE inhibitor at least 24 hours before the desensitization procedure begins.

Anaphylactoid reactions during apheresis of low density lipoproteins

(LDL)

In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions in LDL-apheresis using dextran sulfate.To prevent the anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each procedure for LDL apheresis using high-flow membranes.

Hemodialysis

In patients receiving ACE inhibitors, hemodialysis using high-flow membranes (for example, AN69®) Anaphylactoid reactions were noted. Therefore, it is desirable to use a different type of membrane or to use an antihypertensive drug of another pharmacotherapeutic group.

Cough

Against the background of therapy with ACE inhibitors, a cough appears. By its nature, it is stubborn, unproductive, which passes after the drug is discontinued. Cough caused by ACE inhibitors should be considered in the differential diagnosis of cough.

Surgical procedures / General anesthesia

The use of ACE inhibitors in patients undergoing surgery with general anesthesia can lead to a marked decrease in blood pressure, especially with the use of general anesthetic agents with antihypertensive effects.

It is recommended to stop the use of ACE inhibitors, including lisinopril, 12 hours before surgery,warning the surgeon / anesthesiologist about the use of ACE inhibitors.

Hyperkalemia

Perhaps the development of hyperkalemia. Risk factors for the development of hyperkalemia: renal failure, diabetes mellitus, the use of potassium drugs or drugs that cause an increase in the concentration of potassium in the blood (including heparin), especially in patients with impaired renal function.

In patients at risk of developing symptomatic arterial hypotension, loss of fluid and salts before the start of therapy should be compensated.

Elderly patients

Before starting the preparation Lisinopril NL-KRKA should assess the function of the kidneys and the content of potassium in the blood plasma. The initial dose is selected depending on the degree decrease in blood pressure, especially with a decrease in bcc and CHF (IV functional class by classification NYHA). Such measures allow to avoid a sharp decrease in blood pressure.

Effect on the ability to drive transp. cf. and fur:During the period of drug treatment Lisinopril NL-KRKA is advised to use caution when driving vehicles and engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.when using the drug, dizziness may occur, especially at the beginning of the course of treatment.

Form release / dosage:

Tablets 12.5 mg + 10 mg.

Packaging:

For 10 tablets or 14 tablets in a blister of the combined material PVC / PVDH-aluminum foil.

For 2, 3, 6 blisters (blister for 10 tablets) or 1, 2, 4 blisters (blister for 14 tablets) are placed in a pack of cardboard along with instructions for use.

Storage conditions:At a temperature of no higher than 25 ° C, in the original packaging. Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000699

Date of registration:28.09.2011

Date of cancellation:2016-09-28

The owner of the registration certificate:KRKA-PHARMA, doo, Zagreb, CroatiaKRKA-PHARMA, doo, Zagreb, Croatia Croatia

Manufacturer: & nbsp

KRKA-FARMA, d.o.o. Croatia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp28.12.2015

Illustrated instructions

Instructions

Lisinopril NL-KRKA (Lisinopril NL-KRKA)