Description
Pharmacological action
Combined drug whose action is due to the properties of the components that make up its composition.
Enalapril – an ACE inhibitor, is a prodrug: as a result of its hydrolysis, enalaprilat is formed, which inhibits ACE.
Hydrochlorothiazide is a thiazide diuretic. It acts at the level of the distal renal tubules, increasing the excretion of sodium and chlorine ions.
At the beginning of treatment with hydrochlorothiazide, the volume of fluid in the vessels decreases as a result of increased excretion of sodium and fluid, which leads to a decrease in blood pressure and a decrease in cardiac output.
Due to hyponatremia and a decrease in fluid in the body, RAAS is activated. Reactive increase in the concentration of angiotensin II partially limits the decrease in blood pressure. With continued therapy, the hypotensive effect of hydrochlorothiazide is based on a decrease in OPSS. The activation of the renin-angiotensin-aldosterone system results in metabolic effects on the electrolyte balance of the blood, uric acid, glucose and lipids, which partially neutralizes the effectiveness of antihypertensive treatment.
Despite an effective reduction in blood pressure, thiazide diuretics do not reduce structural changes in the heart and blood vessels. Enalapril enhances the antihypertensive effect: inhibits RAAS, i.e. angiotensin II production and its effects. Additionally reduces the production of aldosterone and enhances the action of bradykinin and the release of prostaglandins. Because it often has its own diuretic effect, this can enhance the effect of hydrochlorothiazide.
Enalapril reduces pre- and afterload, which unloads the left ventricle, reduces the regression of hypertrophy and proliferation of collagen, and prevents damage to myocardial cells. As a result, the heart rate slows down and the load on the heart decreases (in case of chronic heart failure), the coronary blood flow improves, and oxygen consumption by cardiomyocytes decreases. Thus, the sensitivity of the heart to ischemia decreases, and the number of dangerous ventricular arrhythmias also decreases. It has a beneficial effect on cerebral blood flow in patients with arterial hypertension and chronic cardiovascular diseases. It prevents the development of glomerulosclerosis, supports and improves renal function and slows down the course of chronic kidney diseases even in those patients who have not yet developed hypertension.
The antihypertensive effect of ACE inhibitors is known to be higher in patients with hyponatremia, hypovolemia, and elevated serum renin, while the effect of hydrochlorothiazide is independent of serum renin. Therefore, the simultaneous administration of enalapril and hydrochlorothiazide has an additional antihypertensive effect. Moreover, enalapril prevents or weakens the metabolic effects of diuretic therapy and has a beneficial effect on structural changes in the heart and blood vessels.
The simultaneous administration of an ACE inhibitor and hydrochlorothiazide is used when each drug individually is not sufficiently effective or monotherapy is carried out using the maximum dose of the drug, which increases the incidence of undesirable effects. This combination allows you to get a better therapeutic effect with lower doses of enalapril and hydrochlorothiazide and reduce the development of unwanted effects.
The antihypertensive effect of the combination usually lasts for 24 hours
Indications
Arterial hypertension (for patients who are shown combination therapy).
Contraindications
– hypersensitivity to enalapril, hydrochlorothiazide (including other sulfonamide derivatives) and other components of
– anuria, severe renal impairment (creatinine clearance (CC) less than 30 ml / min)
– severe hepatic impairment (more than 9 Child-Pugh score, risk of hepatic encephalopathy)
– history of angioedema associated with the use of previously used ACE inhibitors as well as hereditary or idiopathic angioedema
– simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (CC less than 60 ml / min)
– pregnancy and lactation
– age up to 18 years (effect activity and safety not established)
– lactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Precautions:
– severe stenosis of the aortic orifice, hypertrophic obstructive cardiomyopathy
– coronary heart disease and cerebrovascular diseases (including cerebrovascular insufficiency), because an excessive decrease in blood pressure can lead to the development of myocardial infarction and stroke
– chronic heart failure
– severe atherosclerosis
– bilateral renal artery stenosis, stenosis of a single kidney artery
– severe autoimmune systemic diseases of the connective tissue (including systemic lupus erythematosus) – inhibition of bone marrow hematopoiesis, diabetes mellitus, because thiazide diuretics can reduce glucose tolerance
– hyperkalemia
– condition after kidney transplantation
– impaired liver and / or kidney function (QC 30 ml / min)
– condition, accompanied by a decrease in bcc (as a result of diuretic therapy, with limited intake of salt, diarrhea and vomiting)
– angle-closure glaucoma
– in elderly patients
– hypercalcemia, hyperuricemia, and / or gout
– in patients on high dialysis with membranes (such as AN69®)
Special instructions
Arterial hypotension in patients with impaired water-electrolyte balance
In patients with reduced BCC and / or hyponatremia (as a result of vomiting, diarrhea, the use of diuretics in large doses or following a diet with restriction of salt intake), clinically significant arterial hypotension may develop after the start of therapy with Edarbi® Clough. Hypovolemia and water-electrolyte balance should be adjusted before starting treatment. Transient arterial hypotension is not a contraindication to further treatment, which can be continued after stabilization of blood pressure.
Impaired renal function
In patients with impaired renal function (CC more than 30 ml / min), the drug should be used with caution. It is recommended that you regularly monitor the potassium content and serum creatinine concentration. Such patients require careful dose selection with constant monitoring and control of blood pressure. severe cerebrovascular diseases, aortic stenosis or idiopathic hypertrophic obstructive subaortic stenosis, which prevents the outflow of blood from the left ventricle, severe atherosclerosis, in elderly patients as a result of the risk of developing hypotension and poor blood supply to the heart, brain and kidneys.
Regular monitoring of serum concentration of electrolytes during treatment is necessary to identify possible imbalance and timely adoption of necessary measures. Determination of serum concentration of electrolytes is mandatory for patients with prolonged diarrhea, vomiting.
When using this combination, signs of disturbance of the water-electrolyte balance should be monitored, such as dry mouth, thirst, weakness, drowsiness, increased irritability, If jaundice occurs and the activity of hepatic transaminases increases, treatment should be stopped immediately, patients should be monitored.
Caution is necessary in all patients receiving treatment with hypoglycemic agents for oral administration or insulin, as hydrochlorothiazide can weaken, and enalapril enhance their effect.
Thiazide diuretics can reduce kidney excretion of calcium and cause a slight and transient increase in serum calcium.
Severe hypercalcemia may be a sign of latent hyperparathyroidism. Before conducting a study of the function of the parathyroid glands, thiazide diuretics must be canceled.
During treatment with thiazide diuretics, serum cholesterol and triglyceride concentrations may increase. the incidence of angioedema is higher than among patients of a different race.
Patients with a history of angioedema not associated with ACE inhibitors have an increased risk of developing angioedema when taking any ACE inhibitor.
In patients taking thiazide diuretics, hypersensitivity reactions can develop both in the presence and in the absence of a history of allergic reactions. A deterioration in the course of systemic lupus erythematosus has been reported.
Due to the increased risk of anaphylactic reactions, this combination should not be used in patients undergoing hemodialysis using high-flow polyacrylonitrile membranes (AN 69®), caused by the use of ACE inhibitors.
Effect on the ability to drive vehicles and mechanisms
At the beginning of treatment with this combination, a pronounced decrease in blood pressure, dizziness and drowsiness are possible, which may reduce the ability to drive vehicles and other potentially dangerous activities. Therefore, at the beginning of treatment, it is not recommended to drive vehicles and engage in work that requires an increased concentration of attention and speed of psychomotor reactions.
Ingredients
Active ingredients:
hydrochlorothiazide 12.50 mg,
enalapril maleate 10.00 mg,
Excipients: sodium bicarbonate * 5.10 mg, lactose monohydrate 130.08 mg, starch cornmeal 32.10 mg starch 6.00 mg, talcum 6.00 mg, magnesium stearate 2.00 mg
* 2.68 mg CO2 and 1.10 mg H2O resulting from a chemical reaction between sodium bicarbonate and enalapril maleate, evaporate during the process and are not included in the final tablet weight.
Dosage and administration of
Enap®-NL should be taken regularly at the same time, preferably in the morning, during or after meals, without chewing, washing down with a small amount of liquid. The recommended dose is 1 tablet per day. If necessary, the dose can be increased to the maximum daily dose – 2 tablets, take 1 time per day.
In patients undergoing diuretic therapy, it is recommended to cancel treatment or reduce the dose of diuretics at least 3 days before the start of treatment with Enap®-NL to prevent the development of symptomatic arterial hypotension.
Renal function should be investigated before treatment begins.
Duration of treatment is determined by the physician.
Dose for impaired renal function
Enap®-NL in patients with renal failure (CC 30 ml / min) should be used only if titration of the dose of enalapril has shown the adequacy of the dose contained in the combined preparation of Enap®-NL.
Side effects
From the cardiovascular system: palpitations, various heart rhythm disturbances, marked decrease in blood pressure, orthostatic hypotension, cardiac arrest, myocardial infarction, cerebrovascular stroke, angina pectoris, Raynaud’s syndrome, necrotizing angiitis.
From the digestive system: dry mouth, glossitis, stomatitis, inflammation of the salivary glands, anorexia, nausea, vomiting, diarrhea, constipation, flatulence, epigastric pain, intestinal colic, ileus, pancreatitis, liver failure, hepatitis, jaundice, melena.
From the respiratory system: rhinitis, sinusitis, pharyngitis, hoarseness, bronchospasm, asthma, pneumonia, pulmonary infiltrates, eosinophilic pneumonia, pulmonary embolism, pulmonary infarction, respiratory distress (including pneumonitis and pulmonary edema).
From the side of the central nervous system and peripheral nervous system: depression, ataxia, drowsiness, insomnia, anxiety, nervousness, peripheral neuropathy (paresthesia, dysesthesia).
From the urinary system: oliguria, renal failure, impaired renal function, interstitial nephritis.
From the reproductive system: gynecomastia, decreased potency.
On the part of the sensory organs: impaired vision, damage to taste, impaired smell, tinnitus, conjunctivitis, dry conjunctiva, lacrimation.
From the hemopoietic system: leukocytosis, eosinophilia, neutropenia, leukopenia, agranulocytosis, anemia, hypogemoglobinemia, pancytopenia.
From the side of metabolism: hypokalemia, hyperkalemia, hypomagnesemia, hypercalcemia, hyponatremia, hypochloremic alkalosis, hyperglycemia, glucosuria, hyperuricemia, hypercholesterolemia, hypertriglyceridemia, increased activity of liver enzymes, hyperbilirubinemia.
Dermatological reactions: sweating, rash, shingles, alopecia.
Allergic reactions: urticaria, itching, skin rash, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome, photosensitivity, hypersensitivity reactions (angioedema, thrombocytopenic purpura), anaphylactic reactions.
Other: weakness, fever, lupus-like syndrome described in the literature (fever, myalgia and arthralgia, serositis, vasculitis, skin rash, increased ESR, leukocytosis, eosinophilia, positive test for antinuclear antibodies).
Overdose
In case of overdose, stop using Enap®-NL. Symptomatic and supportive therapy is necessary.
Symptoms: marked decrease in blood pressure with bradycardia or other heart rhythm disturbances, dizziness, cough, increased diuresis, resulting in hypokalemia, hypochloraemia, hyponatremia, convulsions, anxiety, impaired consciousness (including coma), acute renal failure, violation of the acid-base state and water-electrolyte balance of the blood.
Treatment: the patient is transferred to a horizontal position with raised legs. In mild cases, gastric lavage and ingestion of activated charcoal are indicated, in more serious cases, measures aimed at stabilizing blood pressure – intravenous administration of plasma substitutes, infusion of 0.9% sodium chloride solution. The patient must control blood pressure, heart rate, respiratory rate, serum concentration of urea, creatinine, electrolytes and diuresis, if necessary, hemodialysis (enalaprilat excretion rate – 62 ml / min). With bradycardia, refractory to drug therapy, cardiac pacing is performed.
Active ingredient
Hydrochlorothiazide, enalapril
Prescription terms from
drugstores Prescription
lekarstvennaja form
tablets
KRKA d.d. Novo mesto AO, Slovenia
