Renitec, 20 mg tablets 14 pcs

Edema, Hypertension (high blood pressure), Heart failure

Indications

essential hypertension;
renovascular hypertension;
heart failure of any stage.

In patients with clinical manifestations of heart failure, the drug is also indicated for:

increasing patient survival;
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 impaired left ventricular function, the drug is indicated for:

slowing down 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:
reducing the incidence of myocardial infarction;
reducing the frequency of hospitalizations for unstable angina.

Pharmacological effect

Pharmacotherapeutic group: ACE blocker

Pharmacological action

Renitek® (enalapril maleate) refers to drugs that affect the renin-angiotensin system – ACE inhibitors and is a highly specific, long-acting, sulfhydryl group-free ACE inhibitor.

Renitec® (enalapril maleate) is a derivative of two amino acids: L-alanine and L-proline. Enalapril is an ACE inhibitor, which catalyzes the conversion of angiotensin I into the pressor substance angiotensin II. After absorption, enalapril taken orally is converted by hydrolysis into enalaprilat, which inhibits ACE. ACE inhibition leads to a decrease in the concentration of angiotensin II in the blood plasma, which entails an increase in the activity of plasma renin (due to the elimination of the negative feedback to changes in renin production) and a decrease in aldosterone secretion.

ACE is identical to the enzyme kininase II, so enalapril can also block the destruction of bradykinin, a peptide that has a vasodilating effect. The significance of this effect in the therapeutic action of enalapril requires clarification. It is currently believed that the mechanism by which enalapril lowers blood pressure is the suppression of the renin-angiotensin-aldosterone system, which plays an important role in the regulation of blood pressure. Enalapril exhibits antihypertensive effects even in patients with reduced renin concentrations. The decrease in blood pressure is accompanied by a decrease in total peripheral vascular resistance, an increase in cardiac output and no changes or slight changes in heart rate. As a result of taking enalapril, renal blood flow increases, but the level of glomerular filtration remains unchanged. However, in patients with initially reduced glomerular filtration, its level usually increases.

Antihypertensive therapy with enalapril leads to a significant regression of left ventricular hypertrophy and preservation of its systolic function.

Enalapril therapy is accompanied by a beneficial effect on the ratio of lipoprotein fractions and no effect or a beneficial effect on the concentration of total cholesterol.

Taking enalapril by patients with arterial hypertension leads to a decrease in blood pressure regardless of body position: both in a standing position and in a lying position without a significant increase in heart rate.

Symptomatic postural hypotension is rare. In some patients, achieving optimal blood pressure 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 oral dose of enalapril. The onset of the hypotensive effect 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 recommended doses, the antihypertensive effect and hemodynamic effects are maintained for 24 hours.

Enalapril reduces the loss of potassium ions caused by the use of hydrochlorothiazide.

Pharmacokinetics

After oral administration, enalapril is rapidly absorbed, the Cmax of enalapril in the blood serum is achieved within 1 hour after oral administration. The extent of absorption of enalapril maleate when taken orally is approximately 60%. Eating does not affect the absorption of enalapril.

After absorption, enalapril is rapidly hydrolyzed to form the active substance enalaprilat, a powerful ACE inhibitor. Cmax of enalaprilat in the blood serum is observed 3-4 hours after taking a dose of enalapril orally. The duration of absorption and hydrolysis of enalapril is similar for various recommended therapeutic doses.

Enalapril is excreted primarily through the kidneys. The main metabolites detected in urine are enalaprilat, accounting for approximately 40% of the dose, and unchanged enalapril. There are no data on other metabolites of enalapril. The plasma concentration profile of enalaprilat has a long terminal phase, apparently due to the release of ACE-bound enalaprilat. In individuals with normal renal function, a stable concentration of enalaprilat is achieved on the 4th day from the start of taking enalapril. T1/2 of enalapril with a course of oral administration of the drug is 11 hours.

Special instructions

Renitec® should be used with caution in the treatment of patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney, with primary hyperaldosteronism, hyperkalemia, and conditions after kidney transplantation; aortic stenosis, mitral stenosis (with impaired hemodynamic parameters), idiopathic hypertrophic subaortic stenosis; systemic connective tissue diseases; coronary heart disease; cerebrovascular diseases; diabetes mellitus; renal failure (proteinuria – more than 1 g/day); liver failure; in patients on a salt-restricted diet or on hemodialysis; when taken simultaneously with immunosuppressants and diuretics, in elderly patients (over 65 years), inhibition of bone marrow hematopoiesis; conditions accompanied by a decrease in circulating blood volume (including diarrhea, vomiting).

Clinically significant arterial hypotension

Clinically significant hypotension is rarely observed in patients with uncomplicated arterial hypertension. In patients with arterial hypertension receiving Renitec®, arterial hypotension develops more often against the background of hypovolemia, which occurs, for example, as a result of diuretic therapy, salt restriction, in patients on hemodialysis, and also suffering from diarrhea or vomiting. Clinically significant arterial hypotension was also observed in patients with heart failure, accompanied or not accompanied by renal failure. Hypotension occurs more frequently in patients with more severe forms of heart failure, those using higher doses of loop diuretics, hyponatremia, or impaired renal function. In such patients, treatment with Renitec should be initiated under medical supervision, which should be especially careful when changing the dose of Renitec and/or diuretic. Similarly, patients with coronary heart disease and cerebrovascular diseases should be monitored, in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke. If arterial hypotension develops, the patient should be laid down and, if necessary, given intravenous saline sodium chloride solution.

Transient arterial hypotension when taking Renitec is not a contraindication to further treatment with the drug, which can be continued after fluid volume is replenished and blood pressure is normalized. In some patients with heart failure and with normal or low blood pressure, Renitec® may cause an additional decrease in blood pressure. This reaction to the drug can be expected and should not be regarded as a reason to discontinue treatment. In cases where arterial hypotension becomes stable, the dose should be reduced and/or treatment with a diuretic and/or Renitec should be discontinued.

Aortic stenosis/hypertrophic cardiomyopathy

As with all vasodilators, ACE inhibitors should be administered with caution to patients with left ventricular aortic obstruction.

Renal dysfunction

In some patients, hypotension that develops after initiation of treatment with ACE inhibitors may lead to deterioration of renal function. In some cases, acute renal failure has been reported, usually reversible.

In patients with renal failure, it may be necessary to reduce the dose and/or frequency of dosing. In some patients with bilateral renal artery stenosis or arterial stenosis of a solitary kidney, increases in blood urea and serum creatinine were observed. The changes were usually reversible and the values ​​returned to normal after cessation of treatment. This pattern of changes is most likely in patients with renal failure. In some patients who did not have renal disease before treatment, Renitec® in combination with diuretics usually caused a slight and transient increase in blood urea and serum creatinine. In such cases, it may be necessary to reduce the dose and/or discontinue the diuretic and/or Renitec.

Hypersensitivity/Angioedema

When prescribing ACE inhibitors, including Renitec, rare cases of angioedema of the face, extremities, lips, tongue, glottis and/or larynx have been described, occurring during different periods of treatment. In such cases, you should immediately stop treatment with Renitec and establish constant monitoring of the patient to ensure complete disappearance of symptoms. Even in cases where only difficulty swallowing occurs without breathing problems, patients should be under medical supervision for a long time, since therapy with antihistamines and corticosteroids may not be sufficient. Angioedema of the larynx or tongue can be fatal. In cases where swelling is localized to the tongue, glottis or larynx and may cause airway obstruction, appropriate therapy should be promptly initiated, which may include subcutaneous injection of epinephrine (adrenaline) 0.1% solution (0.3-0.5 ml) and/or urgent measures to ensure airway patency.

Patients with a history of angioedema not associated with the use of ACE inhibitors may have an increased risk of its occurrence when treated with an ACE inhibitor. In patients of the Negroid race, the incidence of angioedema when taking ACE inhibitors is higher than in representatives of other races.

Anaphylactic reactions during hyposensitization with an allergen from Hymenoptera venom

In rare cases, patients receiving ACE inhibitors during hyposensitization with an allergen from Hymenoptera venom have developed anaphylactic reactions that pose a threat to the patients’ lives. Such reactions can be avoided if you temporarily stop taking the ACE inhibitor before the onset of hyposensitization.

Patients on hemodialysis

Patients on dialysis using high-flow membranes (eg, AN69®) and concomitantly receiving an ACE inhibitor have experienced anaphylactic reactions in some cases. Therefore, for such patients, it is recommended to use a different type of dialysis membrane or a different group of antihypertensive agents.

Cough

There are reports of cough occurring during treatment with ACE inhibitors. Usually the cough is non-productive, persistent and stops after discontinuation of the drug. Cough due to treatment with an ACE inhibitor should be considered in the differential diagnosis of cough.

Surgery/General anesthesia

During major surgery or during general anesthesia with the use of agents that cause a hypotensive effect, enalapril blocks the formation of angiotensin II secondary to the compensatory release of renin. If a pronounced decrease in blood pressure develops, explained by a similar mechanism, it can be corrected by increasing the volume of administered fluid.

Hyperkalemia

Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, concomitant use of potassium-sparing diuretics (spironolactone, triamterene or amiloride), as well as the use of potassium supplements and salts.

The use of potassium supplements, potassium-sparing diuretics, or potassium-containing salts, especially in patients with renal failure, can lead to a significant increase in serum potassium levels. Hyperkalemia can cause serious, and in some cases fatal, cardiac arrhythmias.

If it is necessary to concomitantly prescribe the above potassium-containing or potassium-increasing drugs, care should be taken and regular monitoring of potassium levels in the blood serum.

Hypoglycemia

Patients with diabetes mellitus receiving oral hypoglycemic agents or insulin should be informed before starting ACE inhibitors of the need to closely monitor blood glucose levels (hypoglycemia), especially during the first month of co-administration of these drugs.

Use in elderly patients

Clinical studies of the efficacy and tolerability of enalapril were similar in older and younger patients.

Impact on the ability to drive a car and/or operate machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (dizziness is possible, especially after taking the initial dose of an ACE inhibitor in patients taking diuretic drugs).

Active ingredient

Enalapril

Composition

Active substance: enalapril

Pregnancy

Use of the drug during pregnancy is not recommended. If pregnancy occurs, Renitec should be stopped immediately. ACE inhibitors can cause disease or death of the fetus or newborn when prescribed to pregnant women during the second and third trimesters of pregnancy. The use of ACE inhibitors during these periods was associated with adverse effects on the fetus and newborn, including the development of arterial hypotension, renal failure, hyperkalemia and/or cranial hypoplasia in the newborn. Oligohydramnios may develop, apparently due to decreased fetal renal function. This complication can lead to contracture of the limbs, deformation of the skull, including its facial part, and hypoplasia of the lungs. When prescribing Renitec, it is necessary to inform the patient about the potential risk to the fetus.

These adverse effects on the embryo and fetus do not appear to be the result of in utero exposure to ACE inhibitors during the first trimester of pregnancy.

Newborns whose mothers took Renitec should be carefully monitored for decreased blood pressure, oliguria and hyperkalemia. Enalapril, which crosses the placenta, can be partially removed from the neonatal circulation by peritoneal dialysis; theoretically it can be removed through exchange transfusion.

Enalapril and enalaprilat are detected in human milk in trace concentrations. If the use of the drug is necessary, the patient should stop breastfeeding.

Contraindications

history of angioedema associated with previous prescription of ACE inhibitors;
hereditary or idiopathic angioedema;
age under 18 years (efficacy and safety have not been established);
hypersensitivity to any of the components of the drug.

Side Effects

In general, the drug is well tolerated. The total incidence of side effects when using Renitec does not exceed that when prescribing placebo. In most cases, side effects are minor, temporary and do not require discontinuation of therapy.

When prescribing the drug, the following side effects are observed: dizziness and headache are the most common. Increased fatigue and asthenia are observed in 2-3% of patients. Other side effects (hypotension, orthostatic hypotension, syncope, nausea, diarrhea, muscle cramps, skin rash and cough) occur in less than 2% of patients. There are rare reports of renal dysfunction, renal failure, oliguria and proteinuria.

Hypersensitivity/Angioedema

In rare cases, angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been observed, and very rarely, intestinal angioedema has been observed.

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, palpitations, arrhythmias, angina pectoris, Raynaud’s syndrome.

From the digestive system: intestinal obstruction, pancreatitis, liver failure, hepatitis (hepatocellular or cholestatic), jaundice, abdominal pain, vomiting, dyspepsia, constipation, anorexia, stomatitis, dry mouth.

Metabolic disorders: hypoglycemia in patients with diabetes mellitus receiving oral hypoglycemic agents or insulin.

From the side of the central nervous system: depression, confusion, drowsiness, insomnia, increased nervousness, paresthesia, dizziness, sleep disturbances, anxiety.

From the respiratory system: pulmonary infiltrates, bronchospasm/bronchial asthma, shortness of breath, rhinorrhea, sore throat, hoarseness.

Skin: increased sweating, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus, pruritus, urticaria, alopecia.

Others: impotence, redness of the skin, taste disturbance, tinnitus, glossitis, blurred vision.

A complex symptom complex has been reported that may include all or some of the following: fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, positive antinuclear antibody test, increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis. Side effects may also include rash, photosensitivity and other skin reactions.

Laboratory parameters: Clinically significant changes in standard laboratory parameters are rarely associated with the use of Renitec. Possible increases in blood urea levels, serum creatinine, increased activity of liver enzymes and/or bilirubin in the blood serum. These changes are usually reversible and normalize after stopping Renitec. Hyperkalemia and hyponatremia sometimes occur.

There are reports of decreased hemoglobin concentrations and hematocrit. There are reports of isolated cases of neutropenia, thrombocytopenia, bone marrow suppression and agranulocytosis, in which a connection with the use of Renitec cannot be excluded.

The following side effects were identified during post-marketing surveillance, but a cause-and-effect relationship with the use of the drug Renitec® has not been established: pneumonia, urological infection, upper respiratory tract infection, bronchitis, cardiac arrest, atrial fibrillation, herpes zoster, melena, ataxia, thromboembolism of the branches of the pulmonary artery, hemolytic anemia, including cases of hemolysis in patients with deficiency glucose-6-phosphate dehydrogenase.

Interaction

When Renitec is prescribed in combination with other antihypertensive drugs, a summation of the effect may be observed.

Serum potassium concentrations usually remain within normal limits. In patients with arterial hypertension treated with Renitec for more than 48 weeks, an increase in serum potassium of up to 0.2 mEq/L is observed.

When Renitec is used concomitantly with diuretics that cause potassium loss, diuretic-induced hypokalemia is usually attenuated by the effect of enalapril.

Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, concomitant use of potassium-sparing diuretics (spironolactone, triamterene or amiloride), as well as the use of potassium supplements and salts. The use of potassium supplements, potassium-sparing diuretics, or potassium-containing salts, especially in patients with renal failure, can lead to a significant increase in serum potassium levels. If it is necessary to concomitantly prescribe the above potassium-containing or potassium-increasing drugs, care should be taken and regular monitoring of potassium levels in the blood serum.

The combined use of ACE inhibitors and hypoglycemic agents (insulin, oral hypoglycemic agents) may enhance the hypoglycemic effect of the latter with the risk of developing hypoglycemia. This phenomenon was generally observed most often during the first weeks of their joint use, as well as in patients with renal failure. In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose levels should be carefully monitored, especially during the first month of co-administration with ACE inhibitors.

ACE inhibitors reduce the excretion of lithium by the kidneys and increase the risk of developing lithium intoxication. If it is necessary to prescribe lithium salts, it is necessary to monitor the level of lithium in the blood serum.

NSAIDs, including selective COX-2 inhibitors, may reduce the effect of diuretics and other antihypertensive drugs. Thus, the antihypertensive effect of ACE inhibitors may be attenuated by NSAIDs, including COX-2 inhibitors.

In some patients with impaired renal function and taking NSAIDs, including COX-2 inhibitors, concomitant use of ACE inhibitors may lead to a further deterioration of renal function. These changes are usually reversible.

A complex of symptoms, including facial flushing, nausea, vomiting and arterial hypotension, has been described in rare cases with the combined use of gold preparations for parenteral use (sodium aurothiomalate) and ACE inhibitors (enalapril).

Overdose

Information on overdose is limited.

Symptoms: pronounced decrease in blood pressure, starting approximately 6 hours after taking the drug, and stupor. Concentrations of enalaprilat in the blood plasma that were 100-200 times higher than the concentrations observed when prescribing therapeutic doses occurred after taking 300 and 440 mg of enalapril, respectively.

Treatment: intravenous infusion of isotonic sodium chloride solution, if possible – infusion of angiotensin II; inducing vomiting. It is possible to remove enalaprilat using hemodialysis.

Storage conditions

At a temperature not exceeding 25 °C.

Manufacturer

Merck Sharp and Dome B.V., The Netherlands