Enalapril-UBF - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) - 0.191 g, starch potato - 0.0207 g, povidone 0.006 g, magnesium stearate 0.0023 g to obtain a tablet weighing 0.23 g

Description:Tablets white or white with a yellowish hue of color, flat-cylindrical shape with a bevel.

ATX: & nbsp

C.09.A.A.02 Enalapril

Pharmacodynamics:

Enalapril - an antihypertensive drug, from the group of ACE inhibitors. Enalapril is a "prodrug": as a result of its hydrolysis, a enalaprilate, which inhibits ACE. The mechanism of its action is associated with a decrease in the formation of angiotensin I angiotensin II, a decrease in the content of which leads to a direct decrease in the release of aldosterone. This reduces the overall peripheral vascular resistance, systolic and diastolic blood pressure (BP), post - and preload on the myocardium.

Expands arteries more than veins, with a reflex increase in heart rate (heart rate) is not noted.

The antihypertensive effect is more pronounced with high renin activity of blood plasma than with normal or reduced its activity. Decrease in blood pressure within the therapeutic limits does not affect cerebral circulation, blood flow in the vessels of the brain is maintained at a sufficient level and against a background of reduced blood pressure. Strengthens coronary and renal blood flow.

With prolonged use of reduced left ventricular hypertrophy and myocyte walls resistive arteries prevents the progression of chronic heart failure and slows the development of left ventricular dilation. Improves the blood supply of the ischemic myocardium. Reduces the aggregation of platelets.

Has some diuretic effect.

Time of onset of hypotensive effect with oral administration -1h, reaches a maximum after 4-6 hours and persists up to 24 hours. In some patients, in order to achieve optimal blood pressure, therapy is needed for several weeks. In chronic heart failure, a noticeable clinical effect is observed with long-term treatment - 6 months or more.

Pharmacokinetics:

After ingestion, 60% of the drug is absorbed. Eating does not affect the absorption of enalapril.

Enalapril binds up to 50% with plasma proteins. Enalapril is rapidly metabolized in the liver to form an active metabolite of enalaprilate, which is a more active ACE inhibitor than enalapril. The connection with the proteins of the blood plasma enalaprilata - 50-60%.

The maximum concentration of enalapril in the blood plasma is reached after 1 hour, enalaprilata 3-4 hours. Enalaprilat easily passes through the histohematological barriers, excluding the blood-brain barrier, a small amount penetrates the placenta and into the breast milk.

The half-life of enalaprilata is about 11 hours. enalapril mainly kidneys - 60% (20% - in the form of enalapril and 40% - in the form of enalaprilata), through the intestine - 33% (6% - in the form of enalapril and 27% - in the form of enalaprilata).

It is removed during hemodialysis (rate 62 ml / min) and peritoneal dialysis.

The degree of absorption and hydrolysis of enalapril are the same for different doses within the recommended therapeutic range. The main metabolites, determined in urine, are enalaprilate, which is approximately 40% of the accepted dose and unchanged enalapril. There are no data on other metabolites of enalapril. The profile of enalaprilate concentration in blood plasma has a long final phase, which is apparently due to its binding to the ACE of enalaprilate

Indications:

arterial hypertension;

- chronic heart failure (as part of combination therapy).

Contraindications:

Hypersensitivity to enalapril and other ACE inhibitors, history of angioedema, associated with treatment with ACE inhibitors, and hereditary or idiopathic angioedema, porphyria, pregnancy, lactation, age under 18 years (efficacy and safety not established).

Hypersensitivity to other components of the drug; lactose intolerance, lactase deficiency, glucose-galactose malabsorption (lactose is included in the formulation).

Carefully:

Use with caution in primary hyperaldosteronism, bilateral, stenosis of the renal arteries, stenosis - artery of a single kidney, hyperkalemia, condition after kidney transplantation; aortic stenosis, mitral stenosis (with hemodynamic disorders), hypertrophic, obstructive cardiomyopathy of autoimmune systemic connective tissue diseases, including scleroderma, systemic lupus erythematosus, ischemic heart disease, cerebrovascular diseases, diabetes mellitus, renal failure (proteinuria, more than 1, g / day), hepatic insufficiency, in patients,observing a diet with restriction of consumption of table salt or being on hemodialysis, while taking with immunosuppressants and saluretics, in elderly people (over 65), oppression of bone marrow hematopoiesis; Conditions accompanied by a decrease in the volume of circulating blood (including diarrhea, vomiting). The use of Enalapril-UBF during pregnancy is not recommended.

At the onset of pregnancy, the drug should be discontinued immediately. ACE inhibitors can cause disease or fetal or neonatal death if given II and III trimesters of pregnancy. The use of ACE inhibitors during this period was accompanied by a negative impact on the fetus and newborn, including the development of arterial hypotension, renal failure, hyperkalemia and / or hypoplasia of the skull bones in a newborn. Perhaps the development of oligohydramnion, apparently due to a decrease in the function of the kidneys of the fetus. This complication can lead to limb contracture, deformation of the bones of the skull, including its facial part, and lung hypoplasia. When prescribing Enalapril-UBF, the patient should be informed of the potential risk to the fetus.Newborns whose mothers have taken Enalapril-UBF should be carefully monitored for the detection of arterial hypotension, oliguria, and hyperkalemia. Enalapril, which penetrates the placenta, can be partially removed from the bloodstream of a newborn by peritoneal dialysis, in theory it can be removed by exchange blood transfusion. Enalapril and enalaprilate in trace concentrations are excreted in breast milk. If you need to use Enalapril-UBF during lactation, breastfeeding should be discontinued.

Pregnancy and lactation:

Enalapril-UBF is contraindicated in pregnancy and lactation.

Dosing and Administration:

Assign inside regardless of the time of ingestion. To ensure the following dosing regimen, it is possible to use enalapril in other dosages: 2.5 mg, 5 mg, 10 mg.

When monotherapy arterial hypertension - the initial dose of 5 mg 1 time per day.

If there is no clinical effect, after 1-2 weeks the dose is increased by 5 mg. After taking the initial dose, patients should be under medical supervision for 2 hours and an additional 1 hour until BP stabilizes.If necessary and fairly good tolerability, the dose can be increased to 40 mg / day. in 2 admission. After 2-3 weeks, go to a maintenance dose of -10 - 40 mg / day, divided into 1-2 admission. With a moderate degree of arterial hypertension, the average daily dose is about 10 mg.

The maximum daily dose of the drug is 40 mg / day.

In the case of appointing patients who are simultaneously receiving diuretics, treatment with a diuretic should be discontinued 2-3 days before the appointment of Enalapril-UBF. If this is not possible, the initial dose of the drug should be 2.5 mg / day.

Patients with hyponatremia (concentration of sodium ions in the serum of blood less than 130 mmol / l) or serum creatinine concentration greater than 0.14 mmol / L initial dose of 2.5 mg once a day. With Renovascular hypertension, the initial dose is 2.5 - 5 mg / day. The maximum daily dose is 20 mg.

In chronic heart failure, the initial dose is 2.5 mg once, then the dose is increased by 2.5 to 5 mg every 3-4 days according to the clinical response to the maximum tolerated dose, depending on the blood pressure, but not more than 1 < 1 40 mg / day. once or in 2 doses.In patients with low systolic blood pressure (less than 110 mm Hg), therapy should be started with a dose of 1.25 mg. The dose should be selected within 2-4 weeks: Week 1 - Day 1-3: 2.5 mg / day in one session, 4-7 days: 5 mg / day in two divided doses; week 2 - 10 mg in one or two doses, week 3 and 4 - 20 mg in one or two doses.

The average maintenance dose is 5-20 mg / day. for 1-2 reception.

The elderly are more likely to have a more pronounced antihypertensive effect and lengthening the duration of the drug, which is associated with a decrease in the rate of excretion of enalapril, so the recommended initial dose for elderly patients is 1.25 mg per day.

In chronic renal failure cumulation occurs with a decrease in filtration of less than 10 ml / min. With the clearance of creatinine (CC) 80-30 ml / min. the dose is usually 5-10 mg / day, with QC up to 30-10 ml / min. -2.5 - 5 mg / day, prikk less than 10 ml / min. - 1,25-2,5 mg / day. only during dialysis days.

The duration of treatment depends on the effectiveness of therapy. With too pronounced decrease in blood pressure, the dose of the drug is gradually reduced.

The drug is used in both monotherapy and in combination with other antihypertensive drugs.

Side effects:

Side effects are classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but not less than 10%; infrequently - not less than 0,1%, but less than -1%; rarely - not less than 0,01%,but less than 0.1%; very rarely, less than 0.01%, including individual messages.

On the part of the hematopoiesis and lymphatic system, rarely: neutropenia, a decrease in hemoglobin and hematocrit, thrombocytopenia, agranulocytosis, oppression of bone marrow hematopoiesis, pancytopenia, lymphadenopathy, autoimmune diseases.

Metabolic disorders: infrequent: exacerbation of gout.

From the side of the central nervous system: very often: dizziness, weakness; often: headache, asthenia, depression; infrequently: insomnia, drowsiness, paresthesia, increased excitability; rarely: unusual: dreams, sleep disturbances; very rarely: confusion, insomnia.

From the sense organs: often - changes in taste; infrequently: noise_; in the ears, blurred vision.

From the cardiovascular system: often: marked decrease in ad, orthostatic hypotension, syncope, retrosternal pain, heart rhythm disturbances (atrial brady or tachycardia, atrial fibrillation), tachycardia, angina pectoris; infrequent: palpitations, myocardial infarction or stroke (due to a pronounced decrease in blood pressure); rarely: thromboembolism of the pulmonary artery branch, Reynaud syndrome.

From the respiratory system: very often: cough; often: dyspnea; infrequently: rhinorrhea, sore throat and hoarseness, bronchospasm; rarely: infiltrates in the lungs, rhinitis, allergic alveolitis / eosinophilic pneumonia.

From the side of the digestive system: very often: nausea; often: diarrhea, abdominal pain, flatulence; infrequently: ileitis, intestinal obstruction, pancreatitis, vomiting, constipation, anorexia, dryness of the oral mucosa, peptic ulcer; rarely: a violation of liver and bile secretion, hepatitis (hepatocellular, or cholestatic), cholestatic jaundice, fulminant liver necrosis, stomatitis / aphthous ulcers, glossitis; very rarely: intestinal angioedema.

Allergic reactions: infrequently: Stevens-Johnson syndrome.

From the skin: often: skin rash; infrequently: multiform exudative erythema, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma, increased sweating / skin itch / urticaria, alopecia, photosensitivity.

On the part of the genitourinary system: infrequently: impaired renal function, acute renal failure, impotence,decreased libido; rarely: oliguria, gynecomastia.

From the musculoskeletal system: often: muscle spasms; infrequently: arthralgia.

Laboratory indicators: often: hyperkalaemia, increased serum creatinine concentration; infrequently: hyperglycemia, hyperuricemia, hypokalemia, hyponatremia, increased urea concentration in blood serum; rarely: increased activity - "hepatic" transaminases and bilirubin concentrations.

Other: describes a symptom complex that may include fever, myalgia and arthralgia, serositis, vasculitis, increased erythrocyte sedimentation rate, leukocytosis and eosinophilia, skin rash, positive antinuclear antibody test.

Also described is a symptom complex that includes flushing of the facial skin, nausea, vomiting and arterial hypotension and can develop with simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate) intravenously.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Symptoms: marked decrease in blood pressure up to the development of collapse, myocardial infarction, acute disturbance of cerebral circulation or thromboembolic complications, convulsions, stupor.

Treatment: the patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage and ingestion of saline are shown, in more severe cases, measures aimed at stabilizing blood pressure: intravenous administration of 0.9 % solution of sodium chloride, plasma substitutes, if necessary - the introduction of angiotensin II, hemodialysis (the rate of excretion of enalaprilate - 62 ml / min.).

Interaction:

Simultaneous use of non-steroidal anti-inflammatory drugs (NSAIDs) (including Selective inhibitors of cyclooxygenase-2 (COX-2)) can weaken the antihypertensive effect of antihypertensive drugs. Thus, the antihypertensive effect of angiotensin II receptor antagonists or ACE inhibitors may be weakened by NSAIDs, including COX-2 inhibitors. NSAIDs and ACE inhibitors have an additive effect on potassium levels in the blood serum, which can lead to impaired renal function, especially in patients with impaired renal function. This effect is reversible.Joint use should be conducted with caution in patients with impaired renal function.

With potassium-sparing diuretics (spironolactone, triamterene, _ amiloride, eplerenone) can lead to hyperkalemia; with lithium salts - to slow down the excretion of lithium (shown control of the concentration of lithium in blood plasma).

Simultaneous administration with antipyretic and analgesic agents can reduce the effectiveness of the drug.

Enalapril weakens the effect of drugs containing theophylline.

The hypotensive effect of enalapril is enhanced by diuretics, methyldopa, nitrates, beta-adrenoblockers, blockers of "slow" calcium channels dihydropyridine series, hydralazine, prazozin.

Immunosuppressants, allopurinol, cytotoxic drugs increase hematotoxicity. Drugs that cause bone marrow depression, increase the risk of developing neutropenia and / or agranulocytosis.

The combined use of ACE inhibitors and hypoglycemic agents (insulin, hypoglycemic agents for oral administration) can enhance the hypoglycemic effect of the latter with the risk of developing hypoglycemia.This is most often observed during the first weeks of joint use, as well as in patients with chronic renal failure.

Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors; while simultaneous use of ACE inhibitors and gold preparations (sodium aurotomy malate) intravenously, a symptom complex is described, including flushing of the facial skin, nausea, vomiting and arterial hypotension; ethanol can enhance the antihypertensive effect of ACE inhibitors.

Special instructions:

In rare cases, with the use of ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant hepatic necrosis develops, sometimes fatal. If jaundice occurs and the activity of "hepatic" transaminases increases, treatment should be stopped with Enalapril-UBF; the drug Enalapril-UBF, like other ACE inhibitors, has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races; Hyperkalemia can develop on the background of therapy with ACE inhibitors, including Enalapril-UBF.Risk factors for hyperkalemia are renal failure, advanced age, diabetes mellitus, some concomitant conditions (decreased circulating blood volume, heart failure in decompensation, metabolic acidosis), simultaneous intake of potassium-sparing diuretics (such as spironolactone, triamterene, amiloride, eplerenone), as well as preparations of potassium or potassium-containing substitutes for table salt and the use of other potassium or potassium-containing substitutes for common salt and the use of other drugs that promote an increase in potassium in the blood plasma (for example, heparin).

Hyperkalemia can lead to serious heart rhythm disturbances, sometimes with a fatal outcome. The combined use of the aforementioned drugs should be carried out with caution in patients receiving ACE inhibitors, anaphylatoid reactions were noted in hemodialysis using high-flow membranes (eg AN69®). Therefore, it is desirable to use a different type of membrane or to use an antihypertensive drug of another pharmacotherapeutic group like all other vasodilators,ACE inhibitors should be used with extreme caution in patients with obstruction of the outflow tract of the left ventricle and avoid their use in the case of cardiogenic shock and hemodynamically significant obstruction of the outflow tract of the left ventricle.

Effect on the ability to drive transp. cf. and fur:When using Enalapril-UBF, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions

Form release / dosage:

Tablets of 10 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinyl chloride film and foil printed lacquered.

On 10,20,30,, 40,50,60,100 tablets in a can of polymer.

Each jar or 1, 2, 3, 4, 5 contour-cell packs, together with instructions for use, are placed in a bundle.

Storage conditions:

In dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children!

Shelf life:

2 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000696

Date of registration:28.09.2011

The owner of the registration certificate:URALBIOFARM, OJSC URALBIOFARM, OJSC Russia

Manufacturer: & nbsp

URALBIOFARM, OJSC Russia

Information update date: & nbsp21.10.2015

Illustrated instructions

Instructions

Enalapril-UBF (Enalapril-UBF)