Instructions Enalozid 12.5 tablets blister No. 30
Composition
active ingredients: enalapril, hydrochlorothiazide;
1 tablet contains: enalapril maleate in terms of 100% substance – 10 mg, hydrochlorothiazide in terms of 100% substance – 12.5 mg;
Excipients: lactose monohydrate, potato starch, povidone, calcium stearate.
Dosage form
Pills.
Main physicochemical properties: tablets of white or white with a cream tint, with a flat surface, a bevel and a score or without a score.
Pharmacotherapeutic group
Combined ACE inhibitor drugs. Enalapril and diuretics. ATC code C09B A02.
Pharmacological properties
Pharmacodynamics
The drug is a combination of an angiotensin-converting enzyme inhibitor (enalapril maleate) and a diuretic (hydrochlorothiazide).
Angiotensin-converting enzyme (ACE) is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the pressor substance angiotensin II. After absorption, enalapril is hydrolyzed to enalaprilat, which inhibits ACE. Inhibition of ACE leads to a decrease in plasma angiotensin II levels, which leads to an increase in plasma renin activity (due to inhibition of the negative feedback loop on renin release) and a decrease in aldosterone secretion.
ACE is identical to kininase II. Enalapril can also block the breakdown of bradykinin, a potent vasodepressor peptide. However, the role of this fact in the therapeutic effects of enalapril remains unknown. While the mechanism by which enalapril lowers blood pressure is primarily associated with inhibition of the renin-angiotensin-aldosterone system, which plays a major role in blood pressure regulation, enalapril may exert an antihypertensive effect even in patients with low-renin hypertension.
Hydrochlorothiazide (HCTZ) is a diuretic and antihypertensive agent that increases plasma renin activity. The antihypertensive effects of the two components are additive and generally last for 24 hours. Although enalapril alone has a hypotensive effect even in patients with low-renin hypertension, concomitant use with hydrochlorothiazide in such patients results in a greater reduction in blood pressure. The enalapril component of the drug generally attenuates the potassium loss caused by hydrochlorothiazide.
Pharmacokinetics
Enalapril maleate
After oral administration, enalapril is rapidly absorbed, reaching peak serum concentrations within 1 hour. Based on urinary excretion, the extent of absorption of oral enalapril is approximately 60–70%.
After absorption, enalapril is rapidly and extensively hydrolyzed to enalaprilat, a potent angiotensin-converting enzyme inhibitor. Peak serum concentrations of enalaprilat are reached 3–4 hours after oral administration of enalapril maleate. Enalapril is excreted primarily by the kidneys. The major components in the urine are enalaprilat, which accounts for approximately 40% of the dose, and unchanged enalapril. Apart from conversion to enalaprilat, there is no evidence of significant metabolism of enalapril. The serum concentration profile of enalaprilat is characterized by a prolonged terminal phase, which is probably due to binding to ACE. In subjects with normal renal function, steady-state serum concentrations of enalaprilat are reached by the 4th day of oral administration of enalapril. The effective half-life of enalaprilat accumulation after multiple oral administration of enalapril is 11 hours. Food intake does not affect the absorption of enalapril from the gastrointestinal tract. The extent of absorption and hydrolysis of enalapril are similar when taking different doses within the recommended therapeutic range.
Hydrochlorothiazide
When plasma levels were monitored for at least 24 hours, the plasma elimination half-life was 5.6–14.8 hours. Hydrochlorothiazide is not metabolized but is rapidly excreted by the kidneys. At least 61% of the oral dose is excreted unchanged within 24 hours. Hydrochlorothiazide crosses the placental barrier and does not cross the blood-brain barrier.
Enalapril/hydrochlorothiazide
Multiple simultaneous administration of enalapril and hydrochlorothiazide has little or no effect on the bioavailability of these drugs. The combination tablet is bioequivalent to its individual components when administered simultaneously.
Indication
Treatment of 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 treatment with angiotensin-converting enzyme 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)).
Contraindicated during hemodialysis.
Clinical status after kidney transplantation.
Severe liver dysfunction.
Anuria, primary hyperaldosteronism.
Treatment-resistant hypokalemia or hyperkalemia.
Refractory hyponatremia.
Symptomatic hyperuricemia (gout).
Pregnant women or women planning to become pregnant (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 maleate and hydrochlorothiazide
Other antihypertensive drugs.
Concomitant use of beta-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 only be administered with careful 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 diuretic therapy) taking NSAIDs, including COX-2 inhibitors, the concomitant use of angiotensin II receptor antagonists and ACE inhibitors has been shown to cause an additive increase in serum potassium with subsequent deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Therefore, this combination should be administered with caution to patients with impaired renal function. Patients should be adequately hydrated. Careful monitoring of renal function is required at the beginning of concomitant therapy and periodically during such treatment.
Enalapril
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) as well as the use of potassium-containing food supplements or salt substitutes may lead to a significant increase in serum potassium. If the above agents are indicated in connection with hypokalemia, they should be used with caution, with regular determination of serum potassium (see section "Special instructions").
Diuretics (thiazide or loop diuretics).
Previous treatment with high doses of diuretics may lead to volume depletion and an increased risk of hypotension at the start of enalapril therapy (see section 4.4). Hypotensive effects can be reduced by discontinuing the diuretic, increasing salt intake, or initiating treatment with low doses of the drug.
Tricyclic antidepressants/antipsychotics/narcotics.
Concomitant use of anesthetics, tricyclic antidepressants, and antipsychotics with ACE inhibitors may lead to a further decrease 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 (sodium aurothiomalate) and concomitant ACE inhibitors, including enalapril.
Concomitant use of ACE inhibitors and mTOR inhibitors (e.g. temsirolimus, sirolimus, everolimus) may increase the risk of angioedema (see section 4.4).
Sympathomimetics.
Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.
Alcohol
Alcohol enhances the hypotensive effect of ACE inhibitors.
Antidiabetic drugs.
Epidemiological studies have shown that concomitant use of ACE inhibitors and antidiabetic agents (insulins, oral hypoglycaemic agents) may increase the blood glucose-lowering effect with a risk of hypoglycaemia. This effect is more likely to occur during the first weeks of concomitant treatment and in patients with impaired renal function.
Acetylsalicylic acid, thrombolytics, beta-blockers.
Enalapril can be used with caution with acetylsalicylic acid (when used as a thrombolytic agent), thrombolytic agents and beta-blockers.
In patients with established atherosclerotic disease, heart failure, or diabetes mellitus with target 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, barbiturates, narcotic analgesics.
Potentiation of orthostatic hypotension may occur.
Antidiabetic drugs (oral antidiabetic agents and insulin).
During thiazide therapy, glucose tolerance may be impaired. 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 imbalance, mainly hypokalemia.
Kaliuretic diuretics (e.g. furosemide), carbenoxolone, laxatives (in case of abuse).
Hydrochlorothiazide may cause increased loss of potassium and/or magnesium.
Pressor amines (e.g., adrenaline).
Thiazides may reduce the response to pressor amines, but not enough to preclude concomitant use.
Cytotoxic drugs (e.g., cyclophosphamide, methotrexate).
Thiazides, including hydrochlorothiazide, may reduce the renal excretion of cytotoxic drugs and enhance their myelosuppressive effect.
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 drugs 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 are isolated reports of hemolytic anemia with the simultaneous use of hydrochlorothiazide and methyldopa.
Cyclosporine.
Concomitant use of cyclosporine may exacerbate hyperuricemia and increase the risk of complications such as gout.
Anticholinergics (e.g. atropine, biperiden).
Increases the bioavailability of thiazide diuretics due to a decrease in gastrointestinal motility and gastric emptying rate.
Alcohol (ethanol), barbiturates, narcotics or antidepressants.
May lead to increased orthostatic hypotension.
Other antihypertensive agents.
Additive effect.
Digitalis glycosides.
Thiazide-induced hypokalemia or hypomagnesemia may lead to the development of digitalis glycoside-induced cardiac arrhythmias.
Drugs that are affected by changes in serum potassium.
Class Ia antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide); Class III antiarrhythmics (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 vincamicin).
Calcium salts.
Thiazide diuretics may increase serum calcium levels by decreasing calcium excretion. If calcium supplements are required, the dose should be adjusted by monitoring serum calcium levels.
Impact on laboratory test results.
Due to their effect on calcium metabolism, thiazides may interfere with the results of parathyroid function tests (see section 4.4).
Carbamazepine.
Given the risk of symptomatic hyponatremia, clinical and biological monitoring is necessary.
Iodinated contrast agents.
In case of diuretic-induced dehydration, the risk of acute renal failure increases, especially when using high doses of contrast media. Patients need to be rehydrated before the administration of iodine-containing drugs.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, acetylsalicylic acid >3 g/day, and nonselective NSAIDs.
When used concomitantly, NSAIDs may weaken the antihypertensive effect of hydrochlorothiazide and enhance the effect of hydrochlorothiazide on serum potassium levels.
Beta-blockers and diazoxide.
Concomitant use of thiazide diuretics, including hydrochlorothiazide, with beta-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
Arterial hypotension and electrolyte imbalance.
Symptomatic hypotension is rarely observed in patients with uncomplicated arterial hypertension. Among patients with arterial hypertension receiving Enalozid 12.5, arterial hypertension develops more often in patients with impaired water and electrolyte metabolism, for example, due to diuretic therapy, salt restriction, dialysis, diarrhea or vomiting. In this case, regular monitoring of serum electrolyte levels is necessary. 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. In such patients, treatment with the drug should be started under medical supervision.
Patients should be monitored for clinical signs of fluid and electrolyte imbalance, such as dehydration, hyponatremia, hypochloremic alkalosis, which may induce hepatic encephalopathy or hepatic coma; hypomagnesemia or hypokalemia, which may occur as a result of diarrhea or vomiting. Serum electrolyte levels should be monitored periodically in such patients.
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. Such a reaction should not be considered a reason for stopping treatment. In cases where arterial hypotension becomes resistant to treatment, the dose should be reduced and/or treatment with the diuretic and/or Enalozid 12.5 should be discontinued.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS).
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. In patients with established atherosclerotic vascular disease, heart failure, or diabetes with target organ damage, dual blockade of the renin-angiotensin-aldosterone system has been reported in several studies 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 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) (see sections “Contraindications” or “Special warnings and precautions for use”).
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 patients with arterial hypertension in the absence of renal insufficiency, when taking enalapril together with a diuretic, an increase in serum urea and creatinine levels is observed. It may be necessary to reduce the dose of enalapril and/or discontinue diuretic therapy. In such cases, the possibility of renal artery stenosis should be considered.
Hyperkalemia.
The combination of enalapril and a diuretic in 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 arterial hypertension.
Application to children.
The safety and effectiveness of the drug in children have not been established.
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 cases of 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 levels, renal function may deteriorate. Treatment of these patients should be started at low doses, with careful dose adjustments and monitoring of renal function.
Patients on hemodialysis.
Anaphylactoid reactions have been reported in some patients dialyzed with high-flux membranes (e.g. AN 69) and treated concomitantly with 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 transplant.
There is no experience with the use of Enalozid 12.5 in patients with a recent kidney transplant. Therefore, treatment with the drug is not recommended for them.
Liver dysfunction.
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.
Neutropenia/agranulocytosis.
Neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. Neutropenia occurs rarely in patients with normal renal function and without specific risk factors. Enalapril should be used with great caution in patients with collagen vascular disease, immunosuppressive therapy, treatment with allopurinol or procainamide, especially if there is a history of renal impairment. Some of these patients have developed severe infections, which sometimes do not respond to intensive antibiotic therapy.
When using enalapril in these patients, periodic monitoring of white blood cell counts is recommended, and the patient should 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, in patients > 70 years of age, in patients with diabetes mellitus, in transient conditions, in particular dehydration, acute cardiac decompensation, metabolic acidosis, and in the case of concomitant use of potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene or amiloride); in the case of use of dietary supplements or salt substitutes containing potassium, as well as 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 (see section 4.5).
Hypoglycemia.
Diabetic patients taking oral antidiabetic agents or insulin require close glycemic control, especially during the first month of treatment with ACE inhibitors.
Some patients treated with angiotensin-converting enzyme inhibitors, including Enalozid 12.5, have developed angioedema of the face, extremities, lips, tongue, glottis and/or larynx. This may occur at any time during treatment. In such cases, Enalozid 12.5 should be discontinued immediately and the patient should be monitored closely 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 who have previously experienced angioedema unrelated to ACE inhibitors may be at increased risk of developing it while taking ACE inhibitors.
Concomitant use of ACE inhibitors and mTOR inhibitors (mammalian target of rapamycin; e.g. temsirolimus, sirolimus, everolimus) may increase the risk of angioedema.
Anaphylactoid reactions during desensitization therapy.
Life-threatening anaphylactoid reactions have been reported rarely in patients receiving ACE inhibitors during desensitization with hymenoptera venom. These reactions can be avoided by temporarily stopping the ACE inhibitor prior to desensitization.
Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis.
Rarely, life-threatening anaphylactoid reactions have been reported in patients receiving ACE inhibitors during LDL apheresis with dextran sulfate. These reactions can be avoided by temporarily discontinuing ACE inhibitor therapy prior to 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.
Surgical operations/anesthesia.
During major surgery or 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.
Racial factor.
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
Kidney dysfunction.
Thiazides may not be effective enough as diuretics for the treatment of patients with impaired renal function, as well as when the creatinine clearance level is 30 ml/min or lower (i.e., in moderate or severe renal insufficiency).
Enalozid 12.5 tablets should not be prescribed to patients with renal insufficiency (creatinine clearance < 80 ml/min) until titration of the individual components of the drug indicates the need for the doses present in the combination tablets.
Liver dysfunction.
Thiazides should be used with caution in patients with impaired liver function or progressive liver disease, since even minor abnormalities in fluid and electrolyte balance may result in 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 effect has been reported at low doses (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 may attenuate the hyperuricemic effect of hydrochlorothiazide.
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 (ACTH).
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 may 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 the blood plasma; treatment with the drug should be discontinued before laboratory testing to assess the function of the parathyroid glands; the drug is capable of increasing the concentration of free bilirubin in the blood serum; hydrochlorothiazide may give a positive result in an anti-doping test.
Increased sensitivity.
Hypersensitivity reactions to hydrochlorothiazide may occur in patients with a predisposition to allergies or in patients with a history of bronchial asthma.
Exacerbation or activation of systemic lupus erythematosus has been observed with the use of thiazide diuretics.
Non-melanoma skin cancer.
The results of two recent pharmacoepidemiological studies (according to Danish national data sources, including the Danish Cancer Registry and the National Register of Prescribed Medicines) have shown a cumulative dose-dependent association between the use of hydrochlorothiazide and the occurrence of basal cell carcinoma and squamous cell carcinoma. The photosensitizing effect of hydrochlorothiazide may be a cause of the development of these pathologies. Patients taking hydrochlorothiazide alone or in combination with other drugs should be informed of the risk of non-melanoma skin cancer and advised to regularly examine their skin for new lesions, as well as changes in existing ones, and to report any suspicious skin lesions.
Suspicious skin lesions are subject to histological examination by biopsy.
Patients should be advised to limit exposure to sunlight and UV rays and to use appropriate protection when exposed to sunlight and UV rays to minimize the risk of skin cancer.
The use of hydrochlorothiazide should also be carefully reconsidered in patients with a history of skin cancer (see section 4.8).
Special precautions for excipients.
Enalozid 12.5 contains lactose. Patients with galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Ability to influence reaction speed when driving vehicles or other mechanisms
When driving a car or operating other mechanical devices, caution should be exercised and the possibility of adverse reactions from the nervous system, including dizziness or drowsiness, should be taken into account.
Use during pregnancy or breastfeeding
ACE inhibitors are contraindicated in pregnant women and women planning to become pregnant (see section “Contraindications”).
Patients who
