Enap, tablets 10 mg 60 pcs

Enap is an antihypertensive drug, an ACE inhibitor. Enalapril is a “prodrug”: as a result of its hydrolysis enalaprilate is formed. The mechanism of action is associated with inhibition of ACE activity under the influence of enalaprilat. This leads to a decrease in angiotensin II formation from angiotensin I, which causes a direct decrease in aldosterone secretion. As a result, there is a decrease in RPS, systolic and diastolic BP, post- and preload on the myocardium.

Dilates arteries to a greater extent than veins, and there is no reflex increase in HR.

Decreases bradykinin degradation and increases prostaglandin synthesis.

The antihypertensive effect is more pronounced at high plasma renin levels than at normal or reduced levels. Reduction of BP within therapeutic limits has no effect on cerebral blood flow. Blood flow in the cerebral vessels is maintained at a sufficient level even against the background of reduced BP. It increases coronary and renal blood flow.

Long-term use reduces hypertrophy of the left ventricular myocardium and myocytes of the walls of the resistive arteries, prevents the progression of heart failure and slows the development of dilatation of the left ventricle. It improves the blood supply to the ischemic myocardium.

Limits platelet aggregation.

Has some diuretic effect.

When the drug is taken orally the hypotensive effect develops in 1 hour, reaches a maximum after 4-6 hours and lasts up to 24 hours. In some patients, therapy for several weeks is necessary to achieve optimal BP level. In cardiac insufficiency, a marked clinical effect is observed with long-term use of 6 months or more.

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Indications

– Arterial hypertension;
– Chronic heart failure (in combination therapy);
– Prevention of the development of clinically significant heart failure in patients with asymptomatic impaired left ventricular function (in combination therapy).

Active ingredient

Composition

1 tablet contains:

Active ingredients:

enalapril maleate 10 mg.

Excipients:

sodium bicarbonate – 5.1 mg,

lactose monohydrate – 124.6 mg,

corn starch – 21.4 mg,

talc – 6 mg,

magnesium stearate – 1.7 mg,

iron oxide red dye (E172) – 1.2 mg.

How to take, the dosage

The drug is taken orally, before, during or after meals, regularly at the same time of the day. The tablets should be swallowed with a small amount of liquid.

If administration of Enap® is missed, the missed dose should be taken. If several hours remain until the next dose according to the regimen, the missed dose of Enap® should not be taken. The dose should never be doubled.
The treatment with Enap® requires regular medical examinations, especially at the beginning of treatment and/or when choosing the optimal dose.

The dose of Enap® should be adjusted according to the level of BP

– Arterial hypertension
The initial dose is 5 to 10 mg once daily, depending on the degree of arterial hypertension.

After the initial dose, patients should be medically monitored for 2 hours and an additional 1 hour until BP stabilizes. If there is no therapeutic effect, the dose of Enap® is increased in 1-2 weeks by 5 mg. Usually maintenance dose is 20 mg/day. If necessary and if tolerated well enough, Enap® dose can be increased to 40 mg/day. Maximum daily dose is 40 mg.

– Renovascular hypertension
Since patients in this group may have especially sensitive BP and renal function to ACE inhibitors, therapy is started with an initial dose of 2.5 mg. The dose is then adjusted according to the patient’s needs. The maximum daily dose is 20 mg.

Cautious use of Enap® should be made in patients who have received prior treatment with diuretics.

– Concomitant treatment of arterial hypertension with diuretics

Patients who are treated with diuretics may have decreased BP on first use of Enap®. Enap® should be used with caution due to possible development of fluid or sodium deficiency. Treatment with diuretics should be discontinued 2 to 3 days before starting Enap® administration.

– Chronic heart failure and prophylaxis of development of clinically significant heart failure in patients with asymptomatic left ventricular dysfunction (in combined therapy)

The initial dose is 2.5 mg once and then the dose is increased by 2.5-5 mg every 3-4 days to maintenance dose of 20 mg/day. The maximum daily dose is 40 mg/day in a single dose or in two doses. The dose should be adjusted over a period of 2-4 weeks.

– Week 1:
Days 1-3: dose – 2.5 mg/day at 1 sitting, Days 4-7: dose – 5 mg/day. daily in 2 doses
– Week 2:
dose – 10 mg in 1-2 doses
– Week 3 and 4:
Dose – 20 mg in 1-2 doses

Renal dysfunction
In patients with impaired renal function the intervals between doses should be increased and/or the dose of Enap® should be decreased.
CKG from 80 ml/min to 30 ml/min: 5 mg-10 mg (initial daily dose)

CKR from 30 ml/min to 10 ml/min: 2.5-5 mg (initial daily dose)

Less than 10 mL/min 2.5 mg on dialysis days

Patients on hemodialysis: 2.5 mg/day is recommended on the day of hemodialysis.
Elderly patients: In this group of patients, the dose is adjusted according to renal function.

Interaction

The simultaneous use of enalapril and potassium-saving diuretics (such as spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing table salt substitutes, as well as other drugs that increase plasma potassium content (e.g., heparin) is not recommended.

Tricyclic antidepressants, antipsychotics (neuroleptics) increase the antihypertensive effect and increase the risk of orthostatic hypotension (additive effect).

The use of diuretics at high doses may lead to hypovolemia (due to decreased blood circulation), and addition of enalapril to therapy may cause marked BP decrease.

In concomitant use of enalapril with lithium preparations – slowing of lithium excretion (increase of cardiotoxic and neurotoxic effects of lithium). Control of plasma lithium concentration is necessary.

The concomitant use of enalapril and beta-adrenoblockers, alpha-adrenoblockers, ganglioblockers, methyldopa or slow calcium channel blockers may further decrease BP.

The concomitant use of other hypotensive agents with ACE inhibitors may increase the risk of leukopenia.

The concomitant use of other hypotensive drugs with ACE inhibitors may increase the risk of hyperkalemia.

Concomitant use of NSAIDs (including selective COX-2 inhibitors) may weaken the antihypertensive effect of ACE inhibitors.
NSAIDs and ACE inhibitors have an additive effect on the increase in serum potassium, which may lead to worsening of renal function, especially in patients with impaired renal function. This effect is reversible.

Antacids may decrease the bioavailability of ACE inhibitors.

Sympathomimetics may decrease the hypotensive effect of ACE inhibitors.

Epidemiological studies suggest that simultaneous use of ACE inhibitors and hypoglycemic agents may lead to the development of hypoglycemia. More often hypoglycemia develops in the first weeks of therapy in patients with impaired renal function. Long-term and controlled clinical trials of enalapril do not confirm these data and do not limit the use of enalapril in patients with diabetes mellitus. Nevertheless, such patients should be under regular medical supervision.

When ACE inhibitors and gold drugs (sodium aurothiomalate) are administered concomitantly by IV, a symptom complex including facial hyperemia, nausea, vomiting and arterial hypotension has been described.

Ethanol may increase the antihypertensive effect of ACE inhibitors.

Enalapril may be used concomitantly with acetylsalicylic acid (as an antiplatelet agent), thrombolytics and beta-adrenoblockers.

It reduces the effect of drugs containing theophylline.

Special Instructions

Arterial hypotension

In case of arterial hypotension, the patient should be placed on his back with a low headboard and, if necessary, the volume of the blood circulation should be corrected by infusion of 0.9% sodium chloride solution. Arterial hypotension occurring after the first dose is not a contraindication for further treatment.

Cautions are required in patients with CHD, significant cerebrovascular disease, aortic stenosis or idiopathic hypertrophic obstructive subaortic stenosis obstructing left ventricular outflow tract, significant atherosclerosis, elderly patients, because of the risk of arterial hypotension.because there is a risk of arterial hypotension and impaired blood supply to the heart, brain, and kidneys.

Potassium-saving diuretics and potassium preparations

The concomitant use of Enap® and potassium-saving diuretics as well as potassium preparations and potassium-containing table salt substitutes is not recommended.

Hemodialysis

In patients receiving ACE inhibitors, anaphylactic reactions have been noted during hemodialysis using high-flow membranes (e.g., AN69®). Therefore, it is advisable to use a different type of membrane or to use an antihypertensive drug from a different pharmacotherapeutic group.

Aortic and/or mitral valve stenosis/hypertrophic obstructive cardiomyopathy (HICMP)
Enap®, like other ACE inhibitors, should be used with particular caution in patients with left ventricular outflow tract obstruction and should be avoided in cases of cardiogenic shock and hemodynamically significant left ventricular outflow tract obstruction.

Kidney transplantation

There is no experience with Enap® in patients who have recently undergone a kidney transplantation.

Disorders of electrolyte-water balance

Several monitoring of serum electrolyte concentrations during therapy is necessary to detect possible electrolyte-water disorders and to initiate appropriate treatment measures. Determination of serum electrolyte concentrations is mandatory for patients with prolonged diarrhea, vomiting.

In patients treated with Enap® it is necessary to detect signs of impaired water-electrolyte balance, such as dry mouth, thirst, weakness, somnolence, hyperexcitability, myalgia and cramps (mainly of the calf muscles), decreased blood pressure, tachycardia, oliguria, and nausea and vomiting.

Allergic reactions/angioneurotic edema

In case of angioedema of the face it is usually sufficient to cancel therapy and give the patient antihistamines. Angioneurotic edema of the tongue, pharynx or larynx can be fatal. In cases of angioedema of the tongue, pharynx or larynx that may result in airway obstruction, 0.3-0.5 ml of epinephrine (adrenaline) solution should be given immediately by injection at a 1:1000 and the airway maintained (intubation or tracheostomy).

The incidence of angioedema is higher among non-Hispanic patients receiving ACE inhibitor therapy than among patients of other racial backgrounds.

Patients with a history of angioedema not associated with ACE inhibitors have an increased risk of developing angioedema when taking any ACE inhibitor.

Because of the increased risk of anaphylactic reactions, Enap® should not be administered to patients on hemodialysis with high flow polyacrylonitrile membranes (AN 69®) undergoing LDL apheresis with dextran sulfate and immediately prior to desensitization with Hymenoptera venom.

Surgery/general anesthesia

Warn the surgeon/anesthesiologist about the use of ACE inhibitors before surgical intervention (including in dentistry).
During surgical interventions or during general anesthesia using agents causing arterial hypotension, ACE inhibitors may block angiotensin II formation in response to compensatory renin release. If a significant decrease in BP develops due to such a mechanism, it may be corrected by increasing the RBC.

Hepatic failure

In rare cases, cholestatic jaundice occurs with ACE inhibitors, with progression resulting in fulminant hepatic necrosis, sometimes fatal. If jaundice or significant increase in liver transaminase activity occurs with ACE inhibitors administration, Enap® should be discontinued.

Neutropenia/agranulocytosis

There have been cases of neutropenia/agranulocytosis, thrombocytopenia and anemia in patients treated with ACE inhibitors. Neutropenia is rare in patients with normal renal function in the absence of other complications. Enap® should be used with great caution in patients with connective tissue diseases (including systemic lupus erythematosus, scleroderma) concomitantly receiving immunosuppressive therapy, allopurinol or procainamide, or with combination of these factors, especially in existing renal function disorders. These patients may develop severe infections that are not amenable to intensive antibiotic therapy. If patients do take Enap®, it is recommended to periodically monitor the number of leukocytes in blood.
The patient should be warned that in case of any signs of infection it is necessary to consult a physician immediately.

Patients with diabetes mellitus

When using Enap® in patients with diabetes mellitus who are receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be monitored regularly during the first month of therapy.

Lithium

The concomitant use of lithium and Enap® is not recommended.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, including enalapril. Risk factors of hyperkalemia are renal insufficiency, elderly age, diabetes mellitus, some concomitant conditions (decreased BOD, decompensated acute heart failure, metabolic acidosis), concomitant use of potassium-saving diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing table salt substitutes and other drugs that increase plasma potassium content (eg, heparin). Hyperkalemia can lead to serious cardiac rhythm disturbances, sometimes fatal. Combined use of the above drugs should be used with caution.

Cough

The use of Enap® may result in a dry, prolonged cough that disappears after discontinuation of the ACE inhibitors, which should be considered in the differential diagnosis of cough with an ACE inhibitor.

Enap®, like other ACE inhibitors, has a less pronounced antihypertensive effect in patients of the Negro race compared to other races.

Impact on driving and operating machinery

When using Enap® , caution should be exercised while driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

– hereditary Quincke’s edema or idiopathic angioedema;
– history of angioedema associated with the use of ACE inhibitors;
– porphyria;
– pregnancy;
– lactation (breastfeeding);
– age under 18 years old (efficacy and safety have not been determined);
– lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
– hypersensitivity to enalapril and other components of Enap preparation;
– hypersensitivity to other ACE inhibitors.

. The preparation should be used with caution in patients with bilateral renal artery stenosis or stenosis of artery of single kidney, with primary hyperaldosteronism, hyperkalemia, after kidney transplantation, with aortic and/or mitral stenosis (with hemodynamic disorders), hypertrophic obstructive cardiomyopathy, states with decreased blood circulation, with systemic connective tissue diseases (incl.ч. scleroderma, systemic lupus erythematosus), CHD, with suppression of medullary hematopoiesis, cerebrovascular disease (including cerebrovascular insufficiency), with diabetes, renal insufficiency (proteinuria – more than 1 g/day.), hepatic insufficiency, in patients on a salt restricted diet or undergoing hemodialysis; concomitantly with immunosuppressants and saluretics; in elderly patients (over 65 years).

Side effects

Classification of the frequency of side effects (WHO): very frequently {> 1/10), frequently (> 1/100 and < 1/10), infrequently (> 1/1000 and < 1/100), rarely (> 1/10 000 and < 1/1000), very rarely (< 1/10 000), including individual reports.

Hematopoietic system: rare – neutropenia, decreased hemoglobin and hematocrit, thrombocytopenia, agranulocytosis, suppression of medullary hematopoiesis, pancytopenia, lymphoadenopathy, autoimmune diseases; very rare – anemia (including aplastic and hemolytic).

Metabolism disorders: infrequent – aggravation of gout and hypoglycemia.

Nervous system disorders: very frequently – dizziness, weakness; frequently – headache, asthenia, depression; infrequently – insomnia, somnolence, paresthesia, increased excitability; rarely – unusual dreams, sleep disorders; very rarely – confusion, insomnia.

Sensory organs: often – changes in taste; infrequent – tinnitus, blurred vision.

Cardiovascular system disorders: often – marked BP decrease, orthostatic hypotension, syncope, chest pain, heart rhythm disorders (atrial brady or tachycardia, atrial fibrillation), tachycardia, angina; infrequently – palpitation, myocardial infarction or stroke (due to marked BP decrease); rarely – pulmonary artery branch thromboembolism, Raynaud syndrome.

The respiratory system: very commonly – cough; frequently – dyspnea; infrequently – rhinorrhea, sore throat and hoarseness, bronchospasm; rarely – pulmonary infiltrates, rhinitis, allergic alveolitis/eosinophilic pneumonia.

Digestive system disorders: very often – nausea; often – diarrhea, abdominal pain, flatulence; infrequently – ileitis, intestinal obstruction, pancreatitis, vomiting, constipation, anorexia, dry oral mucosa, peptic ulcer; rarely – disorders of liver function and biliary excretion, hepatitis (hepatocellular or cholestatic), cholestatic jaundice, fulminant liver necrosis, stomatitis/aphthous ulcers, glossitis; very rare – intestinal angioneurotic edema.

Skin disorders: frequently – skin rash; infrequently – erythema multiforme, exfoliative dermatitis, toxic epidermal necrolysis, vesicles, erythrodermia, profuse sweating, pruritus, urticaria, alopecia, photosensitization.

Urinary system disorders: infrequent – renal dysfunction, acute renal failure; rarely – oliguria.

Perior genital system: infrequent – decreased potency, decreased libido; rarely – gynecomastia.

Musculoskeletal system: frequent – muscle cramps; infrequent – arthralgia.

Laboratory: frequently – hyperkalemia, increased concentration of creatinine in serum; infrequently – hyperglycemia, hyperuricemia, hypokalemia, hyponagremia, increased concentration of urea in serum; rarely – increase of liver transaminases activity and concentration of bilirubin.

Allergic reactions: infrequent – Stevens-Johnson syndrome; rarely – angioedema of the face, lips, tongue, throat, larynx, extremities.

Others: a symptom complex has been described that may include fever, myalgia and arthralgia, serositis, vasculitis, increased erythrocyte sedimentation rate, leukocytosis and eosinophilia, skin rash, positive antinuclear antibody test. Also, a symptom complex has been described that includes facial hyperemia, nausea, vomiting, and arterial hypotension and may develop when ACE inhibitors and gold drugs (sodium aurothiomalate) are used concomitantly by IV.

Overdose

Symptoms: pronounced decrease of BP up to the development of collapse, myocardial infarction, acute cerebral circulation disorder or thromboembolic complications, convulsions, stupor.

Treatment: the patient should be transferred to a horizontal position with a low headboard. In mild cases gastric lavage and ingestion of activated charcoal are indicated; in more severe cases – measures aimed at normalization of BP, intravenous infusion of 0.9% sodium chloride solution, plasma substitutes, if necessary – intravenous angiotensin II infusion, hemodialysis (elimination rate of enalaprilat – 62 ml/min).

Similarities