Diuretics are one of the groups of drugs used in the treatment of hypertension. Indapamide is often prescribed in the complex treatment of arterial hypertension and some cardiovascular diseases; it allows achieving stable and long-term results, including in the elderly.
Composition and release form
Indapamide is produced by different pharmaceutical companies under several names (for example, Indapamide Stada or Teva) in the form:
- long-acting tablets (their name contains the word retard or the letters MB);
- tablets with a special film coating;
- capsules
In all dosage forms, the active ingredient is the same - indapamide. In long-acting tablets, its dosage can be 1.5 mg, and in regular tablets and capsules - only 2.5 mg. Sold in cardboard boxes of 30 or 60 pieces, complete with instructions.
Auxiliary components are represented by colloidal silicon dioxide, magnesium stearate, lactose, microcrystalline cellulose. But each manufacturer has the right to produce medicine using its own technology, so the composition must be specified in the instructions for the product being purchased.
Effect of the drug
Indapamide has a triple effect:
- has a diuretic effect;
- reduces blood pressure;
- dilates blood vessels.
When taking 1.5-2.5 mg of the drug, a hypotensive effect appears, but without a noticeable diuretic effect. This feature allows the drug to be used to lower blood pressure for a long time.
When the dosage is increased, the hypotensive effect does not increase, but the diuretic effect appears.
A noticeable decrease in blood pressure occurs only after 7 days of taking the medicine; a lasting effect can be expected no earlier than after 3 months.
Thanks to the drug, vascular resistance is reduced by reducing the force of contraction of the smooth muscles of the arteries, and the size of the left ventricle of the heart returns to normal.
Pharmacological properties of the drug Indapamide
The first representative of a new class of antihypertensive/diuretic drugs called indolines. It is a sulfonamide derivative with an indole ring in the structure of the molecule. At a dose of 2.5 mg/day it has pronounced and prolonged hypotensive and weak diuretic effects. When prescribed in higher doses, the antihypertensive effect does not significantly increase, while the number of adverse reactions increases. Therefore, you should not exceed the recommended dose. At a dose of 2.5 mg/day it reduces vascular hyperreactivity to norepinephrine and peripheral vascular resistance. Reduces left ventricular hypertrophy in hypertension (arterial hypertension). The antihypertensive effect persists in case of impaired renal function. The vascular mechanism of action of indapamide is due to a decrease in the contractility of vascular smooth muscles due to the effect on transmembrane ion exchange (in particular, a decrease in intracellular calcium transport) and stimulation of the synthesis of prostaglandin E2, which has a vasodilatory and hypotensive effect. It has moderate diuretic and saluretic effects, which are associated with blockade of the reabsorption of sodium, chlorine, water and, to a lesser extent, potassium ions in the proximal and distal convoluted tubules, as well as in the area of the ascending loop of Henle. Does not have a negative effect on lipid metabolism and carbohydrate metabolism. Indapamide is quickly and completely absorbed from the digestive tract; the maximum concentration in blood plasma is achieved between the 1st and 2nd hour after oral administration. Binding to blood plasma proteins is high - 71–79%. Metabolized in the liver. 60–70% of indapamide is excreted in urine (with only 5–7% unchanged), and 20–23% in feces. The half-life is 14–18 hours.
Indications for use
The instructions for use contain information about what Indapamide helps with. It is prescribed for arterial hypertension, as well as for chronic heart failure caused by sodium and water retention in the body.
The drug does not affect the metabolism of carbohydrates and fats, therefore it is indicated:
- people diagnosed with diabetes;
- patients with high cholesterol;
- people with one kidney or on hemodialysis.
Drug interactions Indapamide
It is not recommended to prescribe the following drugs simultaneously with indapamide: lithium salts, sultopride, terfenadine, vincamine, astemizole, erythromycin, pentamidine, bepridil. Caution should be exercised when prescribing indapamide simultaneously with the following drugs: NSAIDs for systemic use, salicylates in high doses, metformin, iodinated contrast agents, some antiarrhythmic drugs (class Ia antiarrhythmic drugs, sotalol and amiodarone), potassium-lowering drugs (amphotericin B - i.v. ), corticosteroids (gluco- and mineralocorticoids for oral use), tetracosactide, laxatives, digitalis preparations. The simultaneous use of potassium-sparing diuretics does not exclude the possibility of developing hypokalemia. Combination with ACE inhibitors increases the risk of developing severe arterial hypotension or renal failure in patients at risk (dehydration, hyponatremia, kidney disease).
Indapamide: how and in what doses to take
The method and regimen of use depend on the prescribed dosage of the drug.
- A 2.5 mg tablet is taken once a day in the morning. If the hypotensive effect does not appear within 14 days, then the dose is increased to 2-3 tablets per day. The maximum daily dose is 10 mg, which should be divided into two doses;
- a long-acting tablet of 1.5 mg is taken once a day in the morning, but if the effectiveness is weak, after 1.5-2 months the treatment should be supplemented with a drug that is not a diuretic. With long-term therapy, increasing the dose is not advisable due to the increased risk of side effects without normalizing blood pressure.
To eliminate edema in chronic heart failure, Indapamide is prescribed at a dose of 5-7.5 mg per day for 7-14 days.
Overdose of the drug Indapamide, symptoms and treatment
Possible symptoms of acute poisoning are caused by disturbances in water and electrolyte balance and are clinically manifested by nausea, vomiting, arterial hypotension, convulsions, dizziness, drowsiness, confusion, polyuria or oliguria, up to anuria due to hypovolemia. First aid includes rapid elimination of the drug taken (gastric lavage, administration of activated charcoal), followed by rehydration therapy and correction of electrolyte disturbances.
List of pharmacies where you can buy Indapamide:
- Moscow
- Saint Petersburg
Is Indapamide safe for pregnant women?
Due to the fact that no serious studies have been conducted on the effect of the drug on pregnant women, tablets and capsules are prohibited during pregnancy. There is a risk of fetoplacental insufficiency, leading to slower fetal development.
The substance can pass into breast milk, therefore, when treating with the drug during lactation, breastfeeding should be stopped.
Indapamide is not suitable for the treatment of physiological edema in pregnancy.
Special instructions for the use of the drug Indapamide
There are no data on the safety of indapamide during pregnancy. The prescription of indapamide as a diuretic for the treatment of edema and hypertension (arterial hypertension) during pregnancy is not justified, since this can lead to fetoplacental ischemia with the risk of developing fetal malnutrition. It is recommended to stop breastfeeding during treatment with indapamide. The use of indapamide in athletes may cause a positive reaction during doping control. During treatment with indapamide, periodic monitoring of serum potassium and sodium levels, as well as uric acid levels in patients with gout is necessary. Secondary hypovolemia following the loss of water and sodium caused by taking the diuretic at the beginning of treatment causes a decrease in glomerular filtration rate. This can lead to an increase in blood levels of urea and plasma creatinine. This transient functional renal failure does not cause adverse effects in individuals with normal renal function, but may increase the severity of pre-existing renal failure. By reducing blood pressure, indapamide can affect the ability to drive vehicles and work with potentially dangerous mechanisms. The antihypertensive effect of indapamide may be enhanced by sympathectomy.
Contraindications and side effects
According to the instructions for use of Indapamide, the drug is contraindicated in:
- hypersensitivity to the main substance;
- acute cerebrovascular accident;
- severe diabetes mellitus;
- advanced form of gout;
- serious renal dysfunction;
- severe liver diseases.
Since the substance removes fluid from the body, it can cause dehydration and a decrease in the concentration of potassium and sodium in the body. In rare cases, arrhythmia and hemolytic anemia may occur.
Main side effects:
- allergies (in the form of skin itching, rash, photosensitivity);
- arrhythmia or tachycardia;
- dry mouth and nausea;
- headache and sleep disturbances;
- epigastric pain;
- constipation or diarrhea.
Taking the drug may provoke changes in well-being due to a decrease in blood pressure, so it is better to avoid activities that require special care.
Perindopril + Indapamide 2.5 mg + 8 mg 30 pcs ➤ instructions for use
Common to perindopril and indapamide Lithium preparations
The simultaneous use of Perindopril PLUS Indapamide with lithium preparations is usually not recommended (see section “Interaction with other drugs”).
Renal dysfunction
Therapy with the drug Perindopril PLUS Indapamide is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min). In some patients with arterial hypertension without previous obvious renal impairment, laboratory signs of functional renal failure may appear during therapy. In this case, treatment with Perindopril PLUS Indapamide should be discontinued. In the future, you can resume combination therapy using low doses of a combination of perindopril and indapamide, or use only one of the drugs.
Such patients require regular monitoring of the content of potassium and creatine ions in the blood serum - 2 weeks after the start of therapy and then every 2 months. Renal failure occurs more often in patients with severe chronic heart failure or underlying renal impairment, including renal artery stenosis.
The drug Perindopril PLUS Indapamide is not recommended for use in cases of bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney.
Arterial hypotension and water-electrolyte imbalance
In the case of initial hyponatremia, there is a risk of sudden development of arterial hypotension (especially in patients with renal artery stenosis). Therefore, when monitoring patients, attention should be paid to possible symptoms of dehydration and decreased plasma electrolytes, for example, after diarrhea or vomiting. Such patients require regular monitoring of blood plasma electrolyte levels.
In case of severe arterial hypotension, intravenous administration of 0.9% sodium chloride solution may be required.
Transient arterial hypotension is not a contraindication for continued therapy. After restoration of blood volume and blood pressure, therapy can be resumed using low doses of a combination of perindopril and indapamide, or only one of the drugs.
Potassium content
The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As with the use of other antihypertensive drugs in combination with a diuretic, regular monitoring of the content of potassium ions in the blood plasma is necessary.
Childhood
The drug Perindopril PLUS Indapamide should not be prescribed to children and adolescents under the age of 18 years due to the lack of data on the effectiveness and safety of the use of perindopril and indapamide both in monotherapy and in combination use in patients of this age group
Indapamide
Hepatic encephalopathy
In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In such a situation, you should immediately stop taking the diuretic.
Photosensitivity
Cases of photosensitivity reactions have been reported with thiazide and thiazide-like diuretics (see section “Side Effects”). If a photosensitivity reaction develops while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.
Water and electrolyte balance
Content of sodium ions in blood plasma
The content of sodium ions in the blood plasma must be determined before starting treatment, and then regularly monitored while taking the drug. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ion levels is indicated for patients with liver cirrhosis and elderly patients (see sections “Side effects” and “Overdose”). Treatment with any diuretics can cause hyponatremia, sometimes with very serious consequences. Hyponatremia accompanied by hypovolemia can lead to dehydration and orthostatic hypotension. A simultaneous decrease in the content of chloride ions can lead to the development of secondary compensatory metabolic alkalosis: the frequency of its occurrence and severity are insignificant.
Content of potassium ions in blood plasma
Therapy with thiazide and thiazide-like diuretics is associated with a high risk of developing hypokalemia. Hypokalemia (less than 3.4 mmol/L) should be avoided in the following high-risk patients: elderly patients, malnourished patients (both those receiving and not receiving concomitant drug therapy), patients with cirrhosis (with edema and ascites) , coronary heart disease, chronic heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of developing arrhythmia.
Patients with a prolonged QT interval, either congenital or drug-induced, are also at increased risk.
Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially arrhythmias, which can be fatal. In all the cases described above, more frequent monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of potassium ion content should be carried out within the first week from the start of therapy.
If hypokalemia is detected, appropriate correction should be made.
Content of calcium ions in blood plasma
Thiazide and thiazide-like diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the content of calcium ions in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. Before studying the function of the parathyroid glands, you should stop taking diuretics.
Plasma glucose concentration
It is necessary to monitor blood glucose concentrations in patients with diabetes mellitus, especially in the presence of hypokalemia.
Uric acid
When the concentration of uric acid in the blood plasma increases during therapy, the frequency of gout attacks may increase.
Diuretics and kidney function
Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine clearance in adult patients below 25 mg/l or 220 µmol/l). In elderly patients, plasma creatinine levels should be assessed taking into account age, weight and gender according to the Cockroft formula:
CC = (140 – age) × weight/0.814 × plasma creatinine concentration,
where: age – in years, weight – in kg, plasma creatinine concentration – in µmol/l.
The formula is suitable for elderly men; for elderly women, the result should be multiplied by a factor of 0.85.
At the beginning of treatment with diuretics, patients due to hypovolemia (due to the excretion of water and sodium ions) may experience a temporary decrease in glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma. This transient functional renal failure is not dangerous for patients with normal renal function, but its severity may increase in patients with renal failure.
Athletes
Indapamide may give a positive reaction during doping control.
Acute myopia and secondary angle-closure glaucoma
Sulfonamides and their derivatives can cause the development of idiosyncratic reactions leading to temporary (transient) myopia and acute angle-closure glaucoma. Without proper treatment, acute angle-closure glaucoma can lead to vision loss. The first step is to stop taking the drug as soon as possible. If intraocular pressure continues to be high, immediate medical or surgical treatment may be required. Risk factors that may lead to the development of acute angle-closure glaucoma include a history of allergies to sulfonamides or penicillin.
Perindopril
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
There is evidence of an increased risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) when ACE inhibitors are used simultaneously with ARB II or aliskiren. Therefore, double blockade of the RAAS by combining an ACE inhibitor with ARA II or aliskiren is not recommended (see sections “Interaction with other drugs” and “Pharmacodynamics”). If a double blockade is absolutely necessary, it should be performed under the strict supervision of a specialist with regular monitoring of renal function, plasma electrolytes and blood pressure.
The use of ACE inhibitors in combination with ARA II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see section "Contraindications").
Potassium-sparing diuretics, potassium supplements, potassium-containing table salt substitutes and food supplements
The simultaneous use of perindopril and potassium-sparing diuretics, as well as potassium preparations, potassium-containing table salt substitutes and food additives is not recommended (see section “Interaction with other drugs”).
Neutropenia/agranulocytosis/thrombocytopenia
There are reports of the development of neutropenia/agranulocytosis, thrombocytopenia and anemia while taking ACE inhibitors. In patients with normal renal function and without concomitant risk factors, neutropenia rarely occurs. Perindopril should be used with extreme caution against the background of systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), as well as while taking immunosuppressants, allopurinol, procainamide, or a combination of these factors, especially in patients with initially impaired renal function.
Some patients developed severe infectious diseases, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should tell their doctor about any signs of infectious diseases (for example, sore throat, fever) (see sections "Interaction with other drugs" and "Side effects").
Anemia
Anemia may develop in patients after kidney transplantation or in patients undergoing hemodialysis. In this case, the decrease in hemoglobin is greater, the higher its initial value. This effect does not appear to be dose-dependent, but may be related to the mechanism of action of ACE inhibitors.
A slight decrease in hemoglobin occurs during the first 6 months, then it remains stable and is completely restored after discontinuation of the drug. In such patients, treatment can be continued, but hematological tests should be carried out regularly.
Hypersensitivity/angioedema
When taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, extremities, lips, tongue, vocal folds and/or larynx may occur (see section “Side effects”). This can happen at any time during therapy. If symptoms occur, Perindopril PLUS Indapamide should be discontinued immediately and the patient should be observed until signs of swelling have completely resolved. If the swelling affects only the face and lips, it usually goes away on its own, although antihistamines can be used as symptomatic therapy.
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. If such symptoms appear, appropriate therapy should be started immediately, for example, epinephrine (adrenaline) administered subcutaneously at a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure airway patency.
A higher risk of developing angioedema has been reported in black patients.
Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group (see section “Contraindications”).
In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal activity of the C-1 esterase enzyme. The diagnosis is made using computed tomography of the abdominal cavity, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.
mTOR (mammalian Target of Rapamycin) inhibitors (eg, temsirolimus, sirolimus, everolimus)
In patients receiving concomitant therapy with mTOR inhibitors, the risk of developing angioedema (including swelling of the airways or tongue with or without impairment of respiratory function) may be increased (see section "Interaction with other drugs").
Anaphylactoid reactions during desensitization
There are isolated reports of the development of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera venom (bees, wasps). ACE inhibitors should be used with caution in patients with a history of allergies or a tendency to allergic reactions undergoing desensitization procedures. The use of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, an anaphylactoid reaction can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the start of the desensitization procedure.
Anaphylactoid reactions during LDL apheresis
In rare cases, life-threatening anaphylactoid reactions have developed in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.
Hemodialysis
Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg, AN69®). Therefore, it is advisable to use a different type of membrane or use an antihypertensive agent of a different pharmacotherapeutic group.
Cough
During therapy with an ACE inhibitor, a dry persistent cough may occur. The cough persists for a long time while taking drugs of this group and disappears after their discontinuation. If a patient develops a dry cough, one should be aware of the possible iatrogenic nature of this symptom. If the doctor believes that ACE inhibitor therapy is necessary for the patient, the drug may be continued.
Risk of arterial hypotension and/or renal failure (in patients with chronic heart failure, fluid and electrolyte imbalance, etc.)
In some pathological conditions, significant activation of the RAAS may be observed, especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (due to a salt-free diet or long-term use of diuretics), in patients with initially low blood pressure, renal artery stenosis, chronic heart failure or cirrhosis of the liver with edema and ascites.
The use of ACE inhibitors causes blockade of the RAAS and therefore may be accompanied by a sharp decrease in blood pressure and/or an increase in plasma creatinine clearance, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug and during the first two weeks of therapy. In rare cases, these conditions develop acutely and during other periods of therapy. In such cases, it is recommended to restart therapy at a lower dose and then gradually increase the dose.
Elderly age
Before starting to take perindopril, it is necessary to assess the functional activity of the kidneys and the content of potassium ions in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of reduction in blood pressure, especially in the case of a decrease in blood volume and loss of electrolytes. Such measures help to avoid a sharp decrease in blood pressure.
Atherosclerosis
The risk of arterial hypotension exists in all patients, however, special care should be taken when using the drug in patients with coronary heart disease and cerebrovascular insufficiency. In such patients, treatment should begin with low doses of the drug.
Renovascular hypertension
The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors may have a beneficial effect in patients both awaiting surgery and in cases where surgery is not possible.
Treatment with the drug Perindopril PLUS Indapamide is not indicated in patients with diagnosed or suspected renal artery stenosis, because Therapy should be started in a hospital setting with lower doses of the combination of perindopril and indapamide.
Heart failure/severe heart failure
In patients with chronic heart failure (functional class IV according to the NYHA classification), treatment with the drug Perindopril PLUS Indapamide is not indicated, because Therapy should begin with lower doses of the combination of perindopril and indapamide under close medical supervision.
Patients with arterial hypertension and coronary heart disease should not stop taking beta-blockers: an ACE inhibitor should be added to beta-blocker therapy.
Diabetes
In patients with type 1 diabetes mellitus, a spontaneous increase in potassium levels in the blood is possible. Treatment of such patients with the drug Perindopril PLUS Indapamide is not indicated, because it should start with minimal doses and be under constant medical supervision. Patients receiving oral hypoglycemic agents or insulin require regular monitoring of plasma glucose concentrations during the first month of therapy with ACE inhibitors (see section “Interaction with other drugs”).
Ethnic differences
Perindopril, like other ACE inhibitors, have a clearly less pronounced antihypertensive effect in patients of the Negroid race compared to representatives of other races. This difference may be due to the fact that black patients with arterial hypertension are more likely to have low renin activity.
Surgery/general anesthesia
Carrying out general anesthesia while taking ACE inhibitors can lead to a significant decrease in blood pressure, especially when using general anesthesia agents that have an antihypertensive effect. It is recommended, if possible, to stop taking long-acting ACE inhibitors, including perindopril, the day before surgery. It is necessary to warn the anesthesiologist that the patient is taking an ACE inhibitor.
Aortic or mitral stenosis/hypertrophic obstructive cardiomyopathy
ACE inhibitors should be prescribed with caution to patients with left ventricular outflow tract obstruction.
Liver failure
In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. As this syndrome progresses, fulminant liver necrosis develops, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice appears or if there is a significant increase in the activity of liver enzymes while taking ACE inhibitors, the patient should stop taking the ACE inhibitor and consult a doctor (see section “Side Effects”).
Hyperkalemia
Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, impaired renal function, advanced age over 70 years, diabetes mellitus, some concomitant conditions (dehydration, acute cardiac decompensation, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing substitutes for table salt, as well as the use of other drugs that help increase the content of potassium ions in the blood plasma (for example, heparins, AFP inhibitors, angiotensin II receptor antagonists, acetylsalicylic acid at a dose of 3 g/day or more , COX-2 inhibitors and non-selective NSAIDs, immunosuppressants such as cyclosporine or tacrolimus, and trimethoprim). The use of potassium supplements, potassium-sparing diuretics, and potassium-containing table salt substitutes can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function. Hyperkalemia can lead to serious, sometimes fatal, heart rhythm disturbances. If combined use of the above drugs is necessary, treatment should be carried out with caution, against the background of regular monitoring of the content of potassium ions in the blood serum (see section “Interaction with other drugs”).
Impact on the ability to drive vehicles and machinery
Care must be taken when driving vehicles and other technical devices that require increased attention and speed of psychomotor reactions (risk of dizziness and fainting).
