Instructions Enalapril-H-Health tablets 10 mg + 25 mg No. 20
Composition
active ingredients: enalapril, hydrochlorothiazide;
1 tablet contains enalapril maleate 10 mg, hydrochlorothiazide 25 mg;
Excipients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, pregelatinized starch, potato starch, magnesium stearate, colloidal anhydrous silicon dioxide, povidone.
Dosage form
Pills.
Main physicochemical properties: tablets of white or white with a creamy tint, flat-cylindrical shape with a score and a bevel.
Pharmacotherapeutic group
Agents acting on the renin-angiotensin system. Combined ACE inhibitor preparations. Enalapril and diuretics. ATC code C09B A02.
Pharmacological properties
The drug contains a combination of two antihypertensive agents. The hypotensive effects of the two components complement each other and persist for 24 hours. The presence of enalapril allows to reduce the loss of potassium associated with the use of hydrochlorothiazide.
Pharmacodynamics. Enalapril is a highly specific competitive ACE antagonist, a prodrug that is converted in the body to the active metabolite enalaprilat.
Enalaprilat inhibits the activity of ACE, as a result of which angiotensin I is not converted to angiotensin II, a substance that has a significant vasoconstrictor effect; it also reduces the secretion of aldosterone, due to which the concentration of angiotensin II and aldosterone in the blood decreases. It inhibits the breakdown of bradykinin, which is a potent vasopressor peptide. The mechanism by which enalapril lowers blood pressure is primarily associated with inhibition of the activity of the renin-angiotensin-aldosterone system, which regulates blood pressure; enalapril can have an antihypertensive effect even in patients with low-renin hypertension.
Pressor (sympathoadrenal) and depressor (kallikrein-kinin and prostaglandin) systems of the body are suppressed and the formation of vascular endothelial factor increases. As a result of these effects, total peripheral vascular resistance, arterial pressure, pressure in the small circle of blood circulation decrease, and cardiac output increases. Enalapril causes a gradual decrease in systolic and diastolic pressure.
The administration of enalapril in hypertension results in a decrease in blood pressure in the patient in both the horizontal and vertical positions without a significant increase in heart rate. Symptomatic postural hypotension occurs infrequently. In some patients, achieving optimal blood pressure reduction may require several weeks of therapy. Abrupt withdrawal of enalapril has not resulted in a rapid increase in blood pressure. Effective inhibition of ACE activity is usually achieved 2–4 hours after oral administration of a single dose of enalapril. The onset of antihypertensive activity is usually recorded 1 hour later, and the peak reduction in blood pressure is achieved 4–6 hours after administration of the drug. The duration of the effect is dose-dependent. However, when used in recommended doses, the antihypertensive and hemodynamic effects were maintained after a single oral dose for at least 24 hours.
In patients with essential hypertension, the reduction in blood pressure was usually accompanied by a decrease in peripheral arterial resistance with some increase in cardiac output and little or no change in heart rate. Renal blood flow increased after enalapril; glomerular filtration rate was unchanged. However, in patients with low glomerular filtration rate before treatment, it usually increased. Antihypertensive therapy with enalapril leads to significant regression of left ventricular hypertrophy with preservation of left ventricular systolic function. Treatment with enalapril was associated with beneficial effects on plasma lipoprotein fractions and with or without beneficial effects on total cholesterol.
The degree of blood pressure reduction observed with the combination of enalapril and hydrochlorothiazide exceeded that with the separate use of the drug components.
Hydrochlorothiazide is an active diuretic, the action of which is due to a decrease in the reabsorption of sodium and chlorine ions in the proximal part of the convoluted tubules. There is also an inhibition of the reabsorption of potassium and bicarbonates. The diuretic effect develops after 1–2 hours, the maximum effect after 4 hours and lasts up to 12 hours. The diuretic effect is manifested in alkalosis and acidosis, does not decrease with prolonged use.
Hydrochlorothiazide increases plasma renin activity. Although enalapril has antihypertensive effects even in patients with low-renin hypertension, concomitant administration of hydrochlorothiazide results in a greater reduction in blood pressure in these patients.
Pharmacokinetics. Enalapril is well absorbed. After oral administration, approximately 60% of enalapril is absorbed in the digestive system. Simultaneous food intake does not affect absorption. It is hydrolyzed in the liver to form enalaprilat. Bioavailability is almost 40%. When taken orally, Cmax of enalapril in blood plasma is observed after 1 hour, of enalaprilat - after 3-4 hours. Enalaprilat easily penetrates histohematological barriers, except for the blood-brain barrier, penetrates the placenta, and is excreted in small amounts in breast milk. Enalaprilat is not biotransformed. Enalaprilat binds to plasma proteins by less than 50%. After taking enalapril, 33% of the dose is excreted in the feces (6% in the form of enalapril, 27% in the form of enalaprilat), with urine - approximately 60% (20% in an unchanged form, 40% in the form of enalaprilat). Renal clearance is 150 ± 44 ml / min. T½ of enalaprilat is 11 hours. In renal failure, T½ increases. Enalaprilat is removed from the body during hemodialysis.
Hydrochlorothiazide is rapidly absorbed after oral administration (60–80%). Hydrochlorothiazide accumulates in erythrocytes 3–9 times more than in plasma. Binding to plasma proteins is 40–70%. The volume of distribution in the terminal elimination phase is 3–6 l/kg (equivalent to 210–420 l for a body weight of 70 kg). Hydrochlorothiazide is poorly metabolized. When plasma levels were assessed for at least 24 hours, the plasma half-life ranged from 5.6 to 14.8 hours. Hydrochlorothiazide is rapidly eliminated by the kidneys, T½ is 10 hours, almost 95% of the substance is excreted in the urine. Hydrochlorothiazide crosses the placenta and into breast milk, but does not cross the blood-brain barrier.
In patients with severe renal insufficiency, T½ of enalaprilat and hydrochlorothiazide increases.
Co-administration of multiple doses of enalapril and hydrochlorothiazide has little or no effect on the bioavailability of these drugs. The combination tablet is bioequivalent to the separate administration of its components.
Indication
Arterial hypertension in patients for whom combination therapy is indicated.
Contraindication
Hypersensitivity to enalapril and other angiotensin-converting enzyme (ACE) inhibitors, hydrochlorothiazide and other sulfonamide derivatives or to other components of the drug; history of angioedema associated with previous treatment with ACE inhibitors; hereditary or idiopathic angioedema; Severe renal impairment (creatinine clearance less than 30 ml/min or serum creatinine level greater than 265 μmol/l (3 mg/100 ml); renal artery stenosis; hemodialysis period; clinical condition after kidney transplantation; severe liver dysfunction; anuria, primary hyperaldosteronism; treatment-resistant hypokalemia or hyperkalemia; refractory hyponatremia; symptomatic hyperuricemia (gout); pregnancy or planning pregnancy (see "Use during pregnancy or breastfeeding").
Enalapril should not be used with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73 m2).
Interaction with other medicinal products and other types of interactions
Enalapril and hydrochlorothiazide
Other antihypertensive drugs. Concomitant use of β-blockers, methyldopa, calcium channel blockers may increase the hypotensive effect of the drug. Concomitant use of nitroglycerin and other nitrates or vasodilators may further reduce blood pressure.
Ganglioblockers or adrenoblockers combined with enalapril should be administered only under close monitoring of the patient's condition.
Lithium preparations. Diuretics or ACE inhibitors reduce the renal clearance of lithium and significantly increase the risk of lithium intoxication, so concomitant use is not recommended.
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid > 3 g/day and non-selective NSAIDs, may reduce the antihypertensive effects of ACE inhibitors, diuretics and/or other antihypertensive drugs. In some patients with impaired renal function (e.g. elderly patients or patients with dehydration, including those receiving diuretics) taking NSAIDs, including COX-2 inhibitors, the concomitant use of angiotensin II receptor antagonists and ACE inhibitors has been shown to have an additive effect on increases in serum potassium and further deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Therefore, the combination should be administered with caution to patients with impaired renal function. Patients should be adequately hydrated and renal function should be closely monitored at the start of concomitant therapy and periodically during such treatment.
Potassium-sparing diuretics and potassium supplements. ACE inhibitors may potentiate hyperkalemia induced by potassium-sparing diuretics. The use of potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene or amiloride) and the use of potassium-containing food supplements or salt substitutes may lead to significant increases in serum potassium. If the above agents are indicated in association with hypokalemia, they should be used with caution and with regular monitoring of serum potassium (see section 4.4).
Diuretics (thiazide or loop diuretics). Previous treatment with high doses of diuretics may result in volume depletion and an increased risk of hypotension at the start of enalapril therapy (see section 4.4). Hypotensive effects may be reduced by discontinuing the diuretic, increasing salt intake, or initiating treatment with a low dose of the drug.
Tricyclic antidepressants/antipsychotics/narcotics: Concomitant use of anesthetics, tricyclic antidepressants, and antipsychotics with ACE inhibitors may result in further reduction in blood pressure.
Gold preparations: Isolated reactions similar to those to nitrites (symptoms of vasodilation, including flushing, facial edema, dizziness, nausea, vomiting, and hypotension) have been observed in patients treated with injectable gold preparations (sodium aurothiomalate) and concomitantly with an ACE inhibitor, including enalapril.
Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.
Alcohol enhances the hypotensive effect of ACE inhibitors.
Antidiabetic agents: Concomitant use of ACE inhibitors and antidiabetic agents (insulins, oral hypoglycaemic agents) may increase the blood glucose-lowering effect with the risk of hypoglycaemia. This effect is more likely during the first weeks of concomitant treatment and in cases of renal impairment.
Acetylsalicylic acid, thrombolytics, β-blockers. Enalapril can be used with caution with acetylsalicylic acid (when used as a thrombolytic agent), thrombolytic agents and β-blockers.
mTOR inhibitors: Concomitant use with mTOR inhibitors (such as temsirolimus, sirolimus, everolimus) may increase the risk of angioedema (see section 4.4).
Concomitant therapy with an ACE inhibitor and an angiotensin receptor antagonist. In patients with established atherosclerotic disease, heart failure, or diabetes mellitus with end-organ damage, concomitant therapy with an ACE inhibitor and an angiotensin receptor antagonist has been reported to be associated with a higher incidence of hypotension, syncope, hyperkalemia, and worsening renal function (including acute renal failure) compared with the use of a renin-angiotensin-aldosterone system agent alone. Dual blockade (e.g., by combining an ACE inhibitor with an angiotensin II receptor antagonist) should be limited to individually defined cases and accompanied by close monitoring of renal function, potassium levels, and blood pressure.
Hydrochlorothiazide
The following drugs may interact with thiazide diuretics when used concomitantly.
Non-depolarizing muscle relaxants (e.g. tubocurarine). Increased sensitivity to the effects of muscle relaxants is possible.
Alcohol (ethanol), barbiturates, narcotic analgesics, antidepressants. Potentiation of orthostatic hypotension is possible.
Antidiabetic agents (oral antidiabetic agents and insulin). Glucose tolerance may be impaired during thiazide therapy. Dosage adjustment may be required. Metformin should be used with caution due to the risk of lactic acidosis due to possible renal failure associated with hydrochlorothiazide.
Cholestyramine and colestipol resins: Anion exchange resins may reduce the absorption of hydrochlorothiazide. Single doses of cholestyramine or colestipol resins reduce the absorption of hydrochlorothiazide from the gastrointestinal tract by 85% and 43%, respectively.
QT prolongation (e.g. procainamide, amiodarone, sotalol). Increased risk of torsades de pointes.
Cardiac glycosides: Hypokalemia may increase the sensitivity or clinical response of the heart to digitalis toxicity (e.g., increased ventricular excitability).
Amphotericin B (parenteral), corticosteroids, adrenocorticotropic hormone, stimulant laxatives, or glycyrrhizin (found in licorice). Hydrochlorothiazide may exacerbate electrolyte imbalances, primarily hypokalemia.
Kaliuretic diuretics (e.g. furosemide), carbenoxolone or laxative abuse. Hydrochlorothiazide may cause increased potassium and/or magnesium loss.
Pressor amines (e.g. adrenaline): Thiazides may reduce the response to pressor amines, but not enough to preclude concomitant use.
Prostaglandin synthase inhibitors: In some patients, their use may reduce the diuretic, natriuretic, and antihypertensive effects of diuretics.
Medicines used to treat gout (probenecid, sulfinpyrazone and allopurinol). Dose adjustment of medicines that promote the excretion of uric acid may be necessary, since hydrochlorothiazide may increase the concentration of uric acid in the blood serum. It may be necessary to increase the dose of probenecid or sulfinpyrazone. Concomitant use of thiazides may increase the incidence of hypersensitivity to allopurinol.
Salicylates. When taking high doses of salicylates, hydrochlorothiazide may enhance their toxic effect on the central nervous system.
Methyldopa: There have been isolated reports of hemolytic anemia with the concomitant use of hydrochlorothiazide and methyldopa.
Cyclosporine: Concomitant use of cyclosporine may increase hyperuricemia and increase the risk of complications such as gout.
Anticholinergic agents (e.g. atropine, biperiden) increase the bioavailability of thiazide diuretics due to a decrease in gastrointestinal motility and gastric emptying rate.
Other antihypertensive agents. Additive effect.
Digitalis glycosides: Thiazide-induced hypokalemia or hypomagnesemia may lead to digitalis glycoside-induced cardiac arrhythmias.
Medicinal products affected by changes in serum potassium: Periodic monitoring of serum potassium and ECG is recommended when losartan/hydrochlorothiazide is co-administered with medicinal products affected by changes in serum potassium (e.g. digitalis glycosides and antiarrhythmics) and with the following medicinal products (including antiarrhythmics) that induce torsades de pointes, hypokalaemia being a predisposing factor for torsades de pointes (ventricular tachycardia):
Class Ia antiarrhythmic drugs (e.g. quinidine, hydroquinidine, disopyramide);
class III antiarrhythmic drugs (e.g. amiodarone, sotalol, dofetilide, ibutilide);
some antipsychotics (e.g. thioridazine, chlorpromazine, levomepromazine, triflupyrazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol);
other drugs (e.g., bepridil, cisapride, diphemanil, intravenous erythromycin, halofantrine, mizolastine, pentamidine, terfenadine, intravenous vincomycin).
Calcium salts. Thiazide diuretics may increase serum calcium levels by decreasing excretion. If calcium supplements are required, the dose should be adjusted based on serum calcium levels.
Effect on laboratory test results: Due to their effect on calcium metabolism, thiazides may interfere with the results of parathyroid function tests.
Carbamazepine: Clinical and biological monitoring is necessary due to the risk of symptomatic hyponatremia.
Iodinated contrast media: Diuretic-induced dehydration increases the risk of acute renal failure, especially with high doses of contrast media. Patients should be rehydrated prior to administration of iodinated contrast media.
NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, acetylsalicylic acid >3 g/day and non-selective NSAIDs. When used concomitantly, NSAIDs may reduce the antihypertensive effect of hydrochlorothiazide and increase the effect of hydrochlorothiazide on serum potassium.
β-Blockers and diazoxide. Concomitant use of thiazide diuretics, including hydrochlorothiazide, with β-blockers may increase the risk of hyperglycemia. Thiazide diuretics, including hydrochlorothiazide, may potentiate the hyperglycemic effect of diazoxide.
Amantadine: Thiazides, including hydrochlorothiazide, may increase the risk of side effects caused by amantadine.
Application features
Enalapril and hydrochlorothiazide
Hypotension and electrolyte imbalance. Symptomatic hypotension is rarely observed in patients with uncomplicated hypertension. When using enalapril, the risk of its development is increased in patients who are salt/volume depleted, for example, due to diuretic therapy, salt restriction, dialysis, the presence of diarrhea or vomiting. Regular monitoring of serum electrolyte levels is necessary in such patients. Symptomatic hypotension has developed more often in patients with more severe forms of heart failure, who were treated with higher doses of loop diuretics, with hyponatremia or impaired renal function. Treatment with the drug should be initiated in such patients under medical supervision.
The approach to treating patients with ischemic heart disease or cerebrovascular disease should be particularly careful, since excessive lowering of blood pressure can lead to myocardial infarction or stroke.
If hypotension develops, the patient should be placed on his back and, if necessary, intravenously administered 0.9% sodium chloride solution. Transient hypotension during treatment is not a contraindication to treatment, which can be continued after normalization of blood pressure and restoration of fluid volume.
In some patients with heart failure and normal or low blood pressure, the drug may further reduce blood pressure. This reaction to the drug is to be expected and should not be considered a reason for discontinuation of treatment. If hypotension becomes refractory to treatment, the dose should be reduced and/or the diuretic and/or the drug should be discontinued.
Dual blockade of the renin-angiotensin-aldosterone system. Dual blockade (e.g., adding an ACE inhibitor to an angiotensin II receptor antagonist) should be limited to isolated cases with close monitoring of blood pressure, renal function, and electrolytes. There is evidence that in patients with established atherosclerotic vascular disease, heart failure, or diabetes with end-organ damage, dual blockade of the renin-angiotensin-aldosterone system is associated with a higher incidence of hypotension, syncope, hyperkalemia, and worsening renal function (including acute renal failure) compared with the use of a single agent acting on the renin-angiotensin-aldosterone system. Enalapril with aliskiren should not be used in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73 m2).
Renal impairment: Renal impairment has been reported with enalapril, particularly in patients with severe heart failure or renal disease, including renal artery stenosis. If diagnosed promptly and treated appropriately, renal impairment associated with enalapril therapy is usually reversible.
In some hypertensive patients without pre-existing renal insufficiency, increases in serum urea and creatinine have been observed when enalapril is administered with a diuretic. It may be necessary to reduce the dose of enalapril and/or discontinue the diuretic. In such cases, the possibility of renal artery stenosis should be considered.
Hyperkalemia. The combination of enalapril and a diuretic at low doses may cause hyperkalemia.
Lithium: Concomitant use of enalapril and lithium is generally not recommended.
Elderly patients. The efficacy and tolerability of enalapril maleate and hydrochlorothiazide administered concomitantly are similar in both elderly and younger adult patients with hypertension.
Enalapril
Aortic or mitral stenosis/hypertrophic cardiomyopathy: As with all vasodilators, ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction and outflow tract obstruction; they should be avoided in cardiogenic shock and hemodynamically significant obstruction.
Renovascular hypertension. Patients with bilateral renal artery stenosis or aortic stenosis of a single healthy kidney who are taking ACE inhibitors are at increased risk of developing arterial hypotension. Even with small changes in serum creatinine, renal function may deteriorate. Treatment in these patients should be initiated under strict medical supervision, with low doses and with careful dose adjustments and monitoring of renal function.
Patients undergoing hemodialysis: Anaphylactoid reactions have been reported in some patients undergoing dialysis using high-flux membranes (e.g. AN 69) and receiving concomitant ACE inhibitors. Therefore, the use of a different type of dialysis membrane or a different class of antihypertensive agent is recommended for these patients.
Kidney transplantation: There is no experience with the use of the drug in patients with a recent kidney transplantation. Therefore, treatment with the drug is not recommended for them.
Hepatic impairment. Very rarely, a syndrome that begins with cholestatic jaundice and progresses to hepatic necrosis, sometimes fatal, has been associated with the use of ACE inhibitors. The mechanism of this syndrome is unknown. Patients receiving ACE inhibitors should discontinue the drug and seek appropriate medical attention if jaundice or significant elevations of liver enzymes occur.
When using enalapril in these patients, periodic monitoring of leukocytes is recommended, and the patient should be warned to inform the doctor of any signs of infection.
Hyperkalemia: During treatment with ACE inhibitors, including enalapril, increases in serum potassium have been observed in some patients. The risk of hyperkalemia is increased in patients with renal insufficiency, with impaired renal function, age > 70 years, with diabetes mellitus, with transient conditions, including dehydration, acute cardiac decompensation, metabolic acidosis, and with concomitant use of potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene, or amiloride); with the use of dietary supplements or salt substitutes containing potassium; and in patients taking other drugs that may cause increases in serum potassium (e.g. heparin). In particular, the use of potassium-sparing diuretics, dietary supplements or salt substitutes containing potassium in patients with impaired renal function may lead to a significant increase in serum potassium. Hyperkalemia may cause serious, sometimes fatal arrhythmias. If concomitant use of enalapril and any of the above-mentioned drugs is considered necessary, they should be used with caution and with regular monitoring of serum potassium.
Hypoglycemia: Diabetic patients taking oral antidiabetic agents or insulin require close glycemic control, especially during the first month of treatment with ACE inhibitors.
Hypersensitivity/angioedema. Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has occasionally been reported in patients treated with ACE inhibitors. This may occur at any time during treatment. In such cases, the drug should be discontinued immediately and the patient should be closely monitored to ensure complete resolution of symptoms. Even if only tongue swelling is present in the absence of respiratory distress, the patient may require prolonged observation, as treatment with antihistamines and corticosteroids may be inadequate.
Fatal angioedema of the larynx or tongue has been reported very rarely. If swelling of the tongue, glottis or larynx occurs, airway obstruction is likely, particularly in patients who have undergone respiratory surgery. In these cases, emergency treatment is required, which may include subcutaneous administration of epinephrine 1:1000 (0.3-0.5 ml) and/or measures to maintain a patent airway.
Angioedema was more common in black patients treated with ACE inhibitors than in patients of other races.
Patients with a history of angioedema unrelated to ACE inhibitors may be at increased risk of developing angioedema while taking ACE inhibitors.
Concomitant use of ACE inhibitors with mTOR inhibitors (e.g. temsirolimus, sirolimus, everolimus) may increase the risk of angioedema.
Anaphylactoid reactions during desensitization therapy. Rarely, patients receiving ACE inhibitors have developed anaphylactoid reactions, which may be life-threatening, during desensitization with a hymenoptera allergen. Such reactions can be avoided by temporarily stopping the ACE inhibitor before the start of desensitization.
Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis. Rarely, life-threatening anaphylactoid reactions may occur during LDL apheresis with dextran sulfate in patients receiving ACE inhibitors. Such reactions can be avoided by temporarily discontinuing ACE inhibitor therapy before each apheresis.
Cough: Cough has been reported with ACE inhibitors. The cough is usually non-productive, persistent, and resolves after discontinuation of the drug. Cough associated with ACE inhibitor therapy should be considered in the differential diagnosis of cough.
Surgery/Anesthesia: During major surgery or during anesthesia with drugs that cause hypotension, enalapril blocks the formation of angiotensin II secondary to compensatory renin release. If hypotension develops, which can be explained by these mechanisms of interaction, it is corrected by increasing the volume of fluid.
Race: As has been reported for other ACE inhibitors, enalapril may be less effective in lowering blood pressure in black hypertensive patients than in non-black patients, possibly because of lower blood renin levels in these patients.
Hydrochlorothiazide
Renal impairment: Thiazides may not be effective diuretics in patients with renal impairment or when creatinine clearance is 30 mL/min or less (i.e., moderate to severe renal impairment).
Hepatic impairment: Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since even minor disturbances of fluid and electrolyte balance may precipitate hepatic coma.
Metabolic and endocrine effects. Thiazide therapy may alter glucose tolerance. Dose adjustment of antidiabetic drugs, including insulin, may be necessary. Thiazide therapy may precipitate manifestations of latent diabetes.
Thiazides may reduce serum sodium, magnesium, and potassium levels.
Elevations in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy; however, minimal or no effects have been reported with hydrochlorothiazide 12.5 mg.
Thiazides may reduce urinary calcium excretion and cause occasional slight increases in serum calcium. Marked hypercalcemia may be a manifestation of latent hyperparathyroidism. Thiazides should be discontinued before thyroid function tests are performed.
Thiazide diuretic therapy may cause hyperuricemia and/or exacerbation of gout in some patients. However, enalapril may increase urinary uric acid levels and thus attenuate the hyperuricemic effect of hydrochlorothiazide.
Although there are no controlled clinical trial data available for patients receiving the combination of enalapril and hydrochlorothiazide, as with patients receiving diuretic therapy, serum electrolyte levels should be measured regularly at appropriate intervals.
Thiazides (including hydrochlorothiazide) may cause fluid and electrolyte imbalance (hypokalemia, hyponatremia, and hypochloremic alkalosis). Dangerous signs of fluid and electrolyte imbalance include dry mouth, thirst, weakness, lethargic sleep, drowsiness, fatigue, muscle pain or cramps, muscle weakness, hypotension, oliguria, tachycardia, and gastrointestinal disturbances (nausea, vomiting).
Although hypokalemia may occur during thiazide diuretic therapy, concomitant therapy with enalapril may reduce diuretic-induced hypokalemia. The risk of hypokalemia may be increased in patients with cirrhosis of the liver, in patients with increased diuresis, in patients with inadequate oral electrolyte intake, and in patients receiving concomitant therapy with corticosteroids or adrenocorticotropic hormone.
In hot weather, patients prone to edema may develop hyponatremia due to blood thinning. Chloride deficiency is usually mild and does not require treatment.
Thiazides increase urinary magnesium excretion, which can lead to hypomagnesemia.
The drug may affect the results of the following laboratory tests:
the drug may reduce the level of protein-bound iodine in blood plasma;
Treatment with the drug should be discontinued before laboratory testing to assess parathyroid function;
the drug is able to increase the concentration of free bilirubin in the blood serum;
Hydrochlorothiazide may cause a positive result in an anti-doping test.
Hypersensitivity: Patients with a predisposition to allergies or a history of bronchial asthma may experience hypersensitivity reactions to hydrochlorothiazide.
Exacerbation or activation of systemic lupus erythematosus has been observed with the use of thiazide diuretics.
Drugs containing sulfonamide or sulfonamide derivatives may cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia, and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or eye pain and usually occur prot
