Composition, form of production and packaging
Tablets are white, triangular in shape, engraved with "MSD 712" on one side and risky on the other.
1 tab.
enalapril maleate 5 mg
[PRING] sodium bicarbonate, lactose monohydrate, corn starch, pregelatinized starch, magnesium stearate.
7 pcs. - blisters (1) - cardboard boxes.
7 pcs. - blisters (2) - cardboard boxes.
7 pcs. - blisters (4) - cardboard boxes.
Tablets pink color, with impregnations, triangular shape, with engraving "MSD 713" on one side and risk - on the other.
1 tab.
enalapril maleate 10 mg
[PRING] sodium bicarbonate, lactose monohydrate, corn starch, corn pregelatinized starch, magnesium stearate, iron oxide red (E172).
7 pcs. - blisters (1) - cardboard boxes.
7 pcs. - blisters (2) - cardboard boxes.
7 pcs. - blisters (4) - cardboard boxes.
100 pieces. - bottles of dark glass (1) - cardboard boxes.
Tablets are light pink in color with a yellowish tinge, triangular in shape, engraved with "MSD 714" on one side and risky on the other.
1 tab.
enalapril maleate 20 mg
[PRING] sodium bicarbonate, lactose monohydrate, corn starch, corn pregelatinized starch, magnesium stearate, iron oxide red (E172), iron oxide yellow (E172).
7 pcs. - blisters (1) - cardboard boxes.
7 pcs. - blisters (2) - cardboard boxes.
7 pcs. - blisters (4) - cardboard boxes.
100 pieces. - bottles of dark glass (1) - cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.
The product description was approved by the manufacturer for the 2009 print edition.
PHARMACHOLOGIC EFFECT
Renitek В® (enalapril maleate) refers to agents that affect the renin-angiotensin system - ACE inhibitors and is a highly specific, long-acting, sulfhydryl group-free ACE inhibitor.
Renitek В® ( enalapril maleate) is a derivative of two amino acids: L-alanine and L-proline. Enalapril is an ACE inhibitor that catalyzes the conversion of angiotensin I into a pressor substance called angiotensin II. After absorption, ingested enalapril is converted by hydrolysis into enalaprilate, which inhibits ACE. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which leads to an increase in renin plasma activity (due to elimination of the reverse negative reaction to changes in renin production) and a decrease in aldosterone secretion.
The ACE is identical to the kinase II enzyme, so enalapril can also block the destruction of bradykinin, a peptide that has a vasodilating effect. The significance of this effect in the therapeutic effect of enalapril needs clarification. At present, it is believed that the mechanism by which enalapril reduces BP is inhibition of the renin-angiotensin-aldosterone system, which plays an important role in the regulation of blood pressure. Enalapril has antihypertensive effect even in patients with reduced renin concentration. Reduction of blood pressure is accompanied by a decrease in total peripheral vascular resistance, an increase in cardiac output and no changes or slight changes in the heart rate. As a result of enalapril intake, renal blood flow increases, but the level of glomerular filtration remains unchanged. However, in patients with initially reduced glomerular filtration, its level usually rises.
Antihypertensive therapy with enalapril leads to a significant regression of left ventricular hypertrophy and the preservation of its systolic function.
Therapy with enalapril is accompanied by a favorable effect on the ratio of lipoprotein fractions and the lack of influence or favorable effect on the concentration of total cholesterol.
The use of enalapril in patients with arterial hypertension leads to a decrease in blood pressure, regardless of the position of the body: both in a standing and lying position without a significant increase in heart rate.
Symptomatic postural hypotension develops rarely. In some patients, achieving an optimal BP reduction may require several weeks of therapy. Interruption of enalapril therapy does not cause a sharp rise in blood pressure.
Effective inhibition of ACE activity usually develops 2-4 hours after a single dose enalapril intake. The onset of antihypertensive action occurs within 1 hour, the maximum decrease in blood pressure is observed 4-6 hours after taking the drug. The duration of action depends on the dose. However, when using the recommended doses, antihypertensive effects and hemodynamic effects are maintained for 24 hours.
Enalapril reduces the loss of potassium ions caused by the use of hydrochlorothiazide.
PHARMACOKINETICS
After ingestion enalapril quickly absorbed, C max enalapril in the serum is reached within 1 h after ingestion. The degree of absorption of enalapril maleate on ingestion is approximately 60%. Eating does not affect the absorption of enalapril.
After absorption, enalapril is rapidly hydrolyzed to form the active substance enalaprilata, a potent ACE inhibitor. C max enalaprilat in the blood serum is observed 3-4 hours after taking enalapril dose inside. The duration of absorption and hydrolysis of enalapril is similar for different recommended therapeutic doses.
Enalapril is excreted mainly through the kidneys. The main metabolites detected in the urine are enalaprilat, which is approximately 40% of the dose and unaltered enalapril. There are no data on other metabolites of enalapril. The enalaprilate concentration profile in the blood plasma has a long final phase, apparently due to the release of the enalaprilate bound to the ACE. In individuals with normal renal function, a stable concentration of enalaprilat is achieved on the 4th day after the start of enalapril. T 1/2 enalapril with a course of administration of the drug inside is 11 hours.
INDICATIONS
- Essential hypertension;
- Renovascular hypertension;
- Heart failure of any stage.
In patients with the presence of clinical manifestations of heart failure the drug is also indicated for:
- increasing the survival rate of patients;
- slowing the progression of heart failure;
- reducing the frequency of hospitalizations for heart failure.
Prevention of the development of clinically significant heart failure
In patients without clinical symptoms of heart failure with left ventricular dysfunction, the drug is indicated for:
- slowing the development of clinical manifestations of heart failure;
- reducing the frequency of hospitalizations for heart failure.
Prevention of Coronary Ischemia
In patients with left ventricular dysfunction, the drug is indicated for:
- decrease in the incidence of myocardial infarction;
- reducing the frequency of hospitalizations for unstable angina.
DOSING MODE
Inside, regardless of food intake, as the absorption of tablets depends on the intake of food.
Arterial hypertension
The initial dose is 10-20 mg, depending on the severity of hypertension and is prescribed 1 time / day. With a mild degree of arterial hypertension, the recommended initial dose is 10 mg / day. At other degrees of arterial hypertension, the initial dose is 20 mg / day with a single dose. Maintenance dose - 1 tab. 20 mg once a day.Dosage is selected individually for each patient, but the dose should not exceed 40 mg / day.
Renovascular hypertension
Since in patients in this group, blood pressure and renal function may be particularly sensitive to ACE inhibition, therapy starts with a low initial dose of 5 mg or less.Then the dose is selected according to the patient's needs. Usually an effective dose of 20 mg / day with daily intake. Care should be taken when treating patients who have received diuretic treatment shortly before.
Concomitant treatment of arterial hypertension with diuretics
After the first reception of Renitek, hypotension may develop. This effect is most likely in patients who are treated with diuretics. The drug is recommended to be administered with caution. such patients may have a deficiency of fluid or sodium. Treatment with diuretics should be discontinued 2-3 days before treatment Renitek.If this is not possible, the initial dose of Renitech should be reduced (to 5 mg or less) to determine the primary effect of the drug. Then the dosage should be selected taking into account the patient's condition.
Dosage for renal failure
The interval between Rhinetek's doses should be increased and / or the dose reduced.
Kidney condition Creatinine clearance ml / min Initial dose mg / day
Minor impairment of function <80> 30 ml / min 5-10 mg
Moderate dysfunction of <30> 10 ml / min 2.5-5 mg
Expressed violations. Usually, such patients are on hemodialysis * <10 ml / min 2.5 mg on dialysis days *
* Enalapril undergoes hemodialysis. Correction of the dose on days when hemodialysis is not performed, should be carried out depending on the level of blood pressure.
Cardiac insufficiency / asymptomatic dysfunction of the left ventricle
The initial dose of Renitek in patients with heart failure or with asymptomatic left ventricular dysfunction is 2.5 mg, with the appointment of the drug should be carried out under close medical supervision to establish the primary effect of the drug on blood pressure. Renitek В® can be used to treat heart failure with severe clinical manifestations, usually in conjunction with diuretics and, when necessary, cardiac glycosides. In the absence of symptomatic hypotension (resulting from Renitek treatment) or after appropriate correction, the dose should be gradually increased to the usual maintenance dose of 20 mg, which is administered either singly or divided into 2 divided doses, depending on the patient's tolerability. The dose can be selected within 2-4 weeks or in shorter periods if there are residual signs and symptoms of heart failure. Such a therapeutic regimen effectively reduces the mortality rates of patients with clinically significant heart failure.
Both before and after the beginning of Renitek treatment, careful monitoring of blood pressure and kidney function in patients with heart failure should be carried out, as there have been reports of the development of arterial hypotension following administration of the drug, followed by (which is observed much more rarely) the occurrence of renal failure. In patients receiving diuretics, the dose of diuretics should be reduced as far as possible before treatment with Renitek. The development of arterial hypotension after taking the first dose of Reniteca does not mean that arterial hypotension will persist with long-term treatment, and does not indicate the need for discontinuation of the drug. When treating Renitek, you should also monitor the potassium level in the serum.
SIDE EFFECT
In general, the drug is well tolerated. The total incidence of side effects with Renitec does not exceed that of placebo. In most cases, the side effects are minor, temporary and do not require the withdrawal of therapy.
When prescribing the drug, the following side effects are observed: dizziness and headache are most common . Increased fatigue and asthenia are observed in 2-3% of patients. Other side effects (arterial hypotension, orthostatic hypotension, syncope, nausea, diarrhea, muscle cramps, skin rash and cough) occur in less than 2% of patients. There are rare reports of violations of kidney function, kidney failure, oliguria and proteinuria.
Hypersensitivity / Angioedema
In rare cases, angioedema has been observed in the face, limbs, lips, tongue, glottis and / or larynx, very rarely - intestinal angioedema.
In very rare cases , the following side effects occur:
From the cardiovascular system: myocardial infarction or stroke, possibly secondary to severe arterial hypotension in patients at risk, chest pain, severe palpitations, rhythm disturbances, angina pectoris, Raynaud's syndrome.
On the part of the digestive system: intestinal obstruction, pancreatitis, hepatic insufficiency, hepatitis (hepatocellular or cholestatic), jaundice, abdominal pain, vomiting, indigestion, constipation, anorexia, stomatitis, dry mouth.
Metabolic disorders: hypoglycemia in patients with diabetes mellitus receiving hypoglycemic agents for ingestion or insulin.
From the side of the central nervous system: depression, confusion, drowsiness, insomnia, increased nervousness, paresthesia, dizziness, sleep disorders, anxiety.
On the part of the respiratory system: pulmonary infiltrates, bronchospasm / bronchial asthma, dyspnea, rhinorrhea, sore throat, hoarseness of the voice.
Skin covers: increased sweating, polymorphic erythema, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus, skin itching, urticaria, alopecia.
Others: impotence, redness of the face, taste disturbance, tinnitus, glossitis, blurred vision.
A complex symptom complex has been reported that may include all or some of the following symptoms: fever, serositis, vasculitis, myalgia / myositis, atrialgia / arthritis, positive antinuclear antibody test, increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis. As side effects, rashes, photosensitivity and other skin reactions may also occur.
Laboratory indicators: clinically significant changes in standard laboratory parameters are rarely associated with the use of Renitec. It is possible to increase the level of urea in the blood, serum creatinine, increased activity of liver enzymes and / or bilirubin in the blood serum. These changes are usually reversible and normalized after discontinuation of Renitec. Sometimes there are hyperkalemia and hyponatremia.
There are reports of a decrease in the concentration of hemoglobin and hematocrit. There are reports of individual cases of neutropenia, thrombocytopenia, suppression of bone marrow function and agranulocytosis, in which it is impossible to exclude links with the use of Renitec.
The following side effects were identified during post-marketing surveillance, but the cause-and-effect relationship with the use of RenitekВ® was not established: pneumonia, urological infection, upper respiratory tract infection, bronchitis, cardiac arrest, atrial fibrillation, herpes zoster, melena, ataxia, thromboembolism of pulmonary artery branches , hemolytic anemia, including cases of hemolysis in patients with deficiency of glucose-6-phosphate dehydrogenase.
CONTRAINDICATIONS
- angioedema in history, associated with the appointment of ACE inhibitors;
- hereditary or idiopathic angioedema;
- age under 18 years (effectiveness and safety not established);
- Hypersensitivity to any of the components of the drug.
PREGNANCY AND LACTATION
Use of the drug during pregnancy is not recommended. At the onset of pregnancy, the reception of Renitek should be immediately stopped. ACE inhibitors can cause disease or death of the fetus or newborn when they are given to pregnant women during the second and third trimesters of pregnancy. The use of ACE inhibitors during these periods was accompanied by a negative impact on the fetus and the newborn, including the development of arterial hypotension, renal failure, hyperkalemia and / or skull hypoplasia in the 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 skull, including its facial part, lung hypoplasia. When appointing Renitek, the patient should be informed of the potential risk to the fetus.
These undesirable effects on the embryo and fetus do not appear to be the result of the intrauterine effect of ACE inhibitors during the first trimester of pregnancy.
Newborns whose mothers took Renitec В® should be carefully monitored in order to detect a decrease in blood pressure, oliguria and hyperkalemia. Enalapril, which penetrates the placenta, can be partially removed from the bloodstream of the newborn by peritoneal dialysis; in theory it can be removed by means of exchange blood transfusion.
Enalapril and enalaprilat are determined in human milk in trace concentrations. In case the use of the drug is necessary, the patient should stop breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
In some patients, arterial hypotension, which develops after the initiation of treatment with ACE inhibitors, can lead to impaired renal function. In some cases, the development of acute renal failure, usually reversible, has been reported.
In patients with renal insufficiency, it may be necessary to reduce the dose and / or frequency of the drug. In some patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, there was an increase in urea in the blood and serum creatinine. Changes were usually reversible and the rates returned to normal after discontinuation of treatment. This type of change is most likely in patients with renal insufficiency. In some patients who did not have renal disease before treatment, Renite В® k, in combination with diuretics, usually caused a slight and transient increase in urea levels in the blood and creatinine in the blood serum. In such cases may require dose reduction and / or cancellation of a diuretic and / or Reniteka.Dolzhen be increased Renitec interval between meals and / or reduce the dose.
Renal Creatinine clearance ml / min Initial Dose mg / day
Minor dysfunction <80> 30 ml / min, 5-10 mg
Moderate dysfunction <30> 10 ml / min 2.5-5 mg
Marked disorders. Typically, such patients are on hemodialysis * <10 ml / min 2.5 mg per dialysis days *
** enalapril subjected to hemodialysis. Correction doses on days when dialysis is not carried out, should be carried out, depending on the blood pressure level.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution in patients with hepatic insufficiency.
APPLICATION FOR CHILDREN
Age 18 years (effectiveness and safety have been established).
APPLICATION IN ELDERLY PATIENTS
The caution in patients older than 65 years.
SPECIAL INSTRUCTIONS
Renitec В® should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, with primary hyperaldosteronism, hyperkalemia, condition after kidney transplantation; aortic stenosis, mitral stenosis (with hemodynamic disorders), idiopathic hypertrophic subaortic stenosis;systemic diseases of connective tissue; coronary heart disease; cerebrovascular diseases; diabetes mellitus; renal disease (proteinuria - more than 1 g / day); hepatic insufficiency; patients on a diet with restriction of salt or in hemodialysis; while admission to immunosuppressants and diuretics, elderly patients (over 65 years), inhibition of bone marrow hematopoiesis; conditions involving decrease of blood volume (including diarrhea, vomiting).
Symptomatic hypotension
Symptomatic hypotension is rarely seen in patients with uncomplicated hypertension. In patients with hypertension receiving Renitec В®, Hypotension usually develops on the background of hypovolemia that arises, for example, as a result of diuretic therapy, limiting salt intake, patients on hemodialysis, as well as suffering from diarrhea or vomiting. Symptomatic hypotension was observed in patients with heart failure, with or without accompanied by renal insufficiency. Hypotension is observed more frequently in patients with more severe forms of heart failure, in which higher doses of loop diuretics, hyponatremia or with impaired renal function. In these patients, treatment Renitec should be started under medical supervision, which should be particularly careful when changing the dose of Renitec and / or a diuretic.Similarly, should be monitored for patients with coronary heart disease as well as cerebral vascular disease, in which a sharp decrease in blood pressure can lead to heart attack or stroke. With the development of hypotension patient should be laid and, if necessary, administer intravenously physiological sodium chloride solution.
Transient hypotension when receiving Renitec is not a contraindication to further treatment drug, which can be continued after the fill fluid volume and blood pressure normalization. Unekotoryh patients with heart failure and normal or reduced AD Renitek В® can cause a further reduction in blood pressure. This reaction to the drug can be expected and should not be regarded as a reason for discontinuation of treatment. In cases where hypotension takes a stable character, should reduce the dose and / or discontinue the diuretic and / or Renitec.
Aortic stenosis / hypertrophic cardiomyopathy
As with all vasodilators patients with obstruction of the aortic orifice of the left ventricle ACE inhibitors should be used with caution.
Impaired renal function
In some patients, hypotension, developing after initiation of treatment with ACE inhibitors, may lead to a deterioration of renal function. In some cases, it was reported on the development of acute renal failure, usually reversible.
In patients with renal failure may need to reduce the dosage and / or frequency of dosing. In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney was observed elevated levels of blood urea and serum creatinine. Changes usually worn reversible and performance returned to normal after discontinuation of treatment. This pattern of change is most likely in patients with renal insufficiency. Unekotoryh patients with renal disease not detected before treatment RenitekВ® in combination with diuretics generally caused a slight and transient increase in the blood urea and creatinine in the blood serum. In such cases it may require dose reduction and / or cancellation of a diuretic and / or Renitec.
Hypersensitivity / Angioedema
When assigning ACE inhibitors, including Renitek, described rare cases angioedema face, extremities, lips, tongue, glottis and / or throat, emerging in different periods of treatment. In such cases, you should immediately discontinue treatment Renitec and establish a permanent observation of the patient to ensure that the complete disappearance of symptoms. Even in cases where there is only difficulty swallowing without respiratory disorders, patients need a long time to be under medical supervision, since therapy with antihistamines and corticosteroids may not be sufficient. Angioneurotic edema of the larynx or tongue can lead to death. In cases where the swelling is localized in the tongue, glottis or larynx, and may cause airway obstruction,should quickly start appropriate therapy, which may include subcutaneous administration of epinephrine solution (adrenaline) 0.1% (0.3-0.5 mL) and / or emergency measures to ensure airway patency.
Patients with a history of angioneurotic edema, not associated with use of ACE inhibitors that may have an increased risk of occurrence and in the treatment of an ACE inhibitor. Patients blacks incidence of angioedema while receiving an ACE inhibitor is higher than that of other races.
Anaphylactic reactions during allergen giposensibilyuatsii of Hymenoptera venom
In rare cases, patients receiving ACE inhibitors during desensitization of allergen Hymenoptera venom, developed anaphylactic reactions that threaten the lives of patients. Such reactions can be avoided if before the start of desensitization to temporarily stop taking the ACE inhibitor.
Patients on hemodialysis
Patients who are on dialysis using high-throughput membrane (eg, AN69В®) and simultaneously treated with an ACE inhibitor, in some cases, developed anaphylactic reactions. Therefore, for these patients, it is recommended the use of dialysis membranes or other types of antihypertensive agents other group.
Cough
has been reported in the treatment of cough with ACE inhibitors. Typically, a cough is non-productive, permanent and ceases after discontinuation of the drug. Cough due to ACE inhibitor therapy should be considered in the differential diagnosis of cough.
Surgery / general anesthesia
During major surgery or during general anesthesia with the use of funds, causing hypotensive effect, enalapril blocks angiotensin II formation secondary to compensatory renin release. If it develops a marked reduction in blood pressure, explained by such a mechanism, it is possible to adjust the increase in the volume of fluid injected.
Hyperkalemia
risk factors for the development of hyperkalemia are renal failure, diabetes, co-administration of potassium-sparing diuretics (spironolactone, triamterene or amiloride), and the use of potassium-containing additives and salts.
The use of potassium supplements, potassium-sparing diuretics or potassium-containing salt, especially in patients with renal failure may lead to a significant increase in potassium in serum. Hyperkalemia can cause serious, in some cases fatal, heart rhythm disturbances.
If necessary, concomitant potassium-purpose or enhance the potassium content of the above formulations, care should be taken regularly monitor the content of potassium in serum.
hypoglycemia
Patients with diabetes receiving hypoglycemic agents for oral or insulin before the start of ACE inhibitors need to be informed about the need for careful monitoring of blood glucose (hypoglycemia), especially during the first month of combined use of these drugs.
Use in elderly patients
Clinical studies of the efficacy and tolerability of enalapril were similar in elderly and younger patients.
Effects on ability to drive and / or use machines
During treatment, care must be taken when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions (dizziness, especially after receiving the starting dose of ACE inhibitor in patients taking diuretic drugs).
OVERDOSE
Data on overdose are limited.
Symptoms: marked reduction of blood pressure, starting after about 6 hours after ingestion, and stupor. Enalaprilat concentration in blood plasma in excess of 100-200 times the concentration observed in the appointment of therapeutic doses, appeared after receiving respectively 300 and 440 mg of enalapril.
Treatment: / in infusion of isotonic sodium chloride solution, if possible - infusion of angiotensin II; induced vomiting. Enalaprilat possible removal by hemodialysis.
DRUG INTERACTION
In the appointment of Renitec in combination with other antihypertensive agents summation effect can be observed.
The concentration of potassium in serum is typically within norm. In patients with hypertension, Renitec treated more than 48 weeks, an increase in serum potassium to 0.2 meq / l.
When the joint application Renitec with diuretics, cause loss of potassium, hypokalemia, caused by the action of diuretics usually attenuated by the effect of enalapril.
Risk factors for the development of hyperkalemia are renal failure, diabetes, co-administration of potassium-sparing diuretics (spironolactone, triamterene or amiloride), and the use of potassium-containing additives and salts. The use of potassium supplements, potassium-sparing diuretics or potassium-containing salt, especially in patients with renal failure may lead to a significant increase in potassium in serum. If necessary, concomitant potassium-purpose or enhance the potassium content of the above formulations, care should be taken regularly monitor the content of potassium in serum.
The combined use of ACE inhibitors and hypoglycemic agents (insulin, hypoglycemic agents for oral administration) can enhance the hypoglycemic effect of the latter with risk for hypoglycemia. This phenomenon is usually the most frequently observed during the first weeks of their joint application, as well as in patients with renal insufficiency. In patients with diabetes receiving hypoglycemic agents for oral or insulin should be carefully monitored blood glucose levels, especially during the first month of combined use of ACE inhibitors.
ACE inhibitors reduce the excretion of lithium by the kidneys and increase the risk of lithium toxicity. If desired destination lithium salts necessary to monitor the level of lithium in serum.
NSAIDs, including selective inhibitors of COX-2 may reduce the effect of diuretics or other antihypertensives. Thus, the antihypertensive effect of the ACE inhibitors may be attenuated NSAIDs, including COX-2 inhibitors.
In some patients with impaired renal function, and taking NSAIDs, including COX-2 inhibitors, concurrent use of ACE inhibitors may lead to further deterioration of kidney function. These changes are usually reversible.
Symptom, including facial flushing, nausea, vomiting, and hypotension, in rare cases described in the combined use of gold preparations for parenteral use (sodium aurothiomalate) and ACE inhibitors (enalapril).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Keep out of the reach of children at a temperature of no higher than 25 В° C. Shelf life - 2 years 6 months.
