Indapamide: review and instructions for use

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.

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.

Indapamide

Undesirable drug combinations

— Lithium preparations:

With the simultaneous use of indapamide and lithium preparations, as well as when following a salt-free diet, an increase in the concentration of lithium in the blood plasma may be observed due to a decrease in its excretion, accompanied by the appearance of signs of overdose. If necessary, diuretics can be used in combination with lithium preparations, and the lithium content in the blood plasma should be monitored and the dose of the drug should be adjusted accordingly.

Combinations of drugs requiring special attention

- Drugs that can cause aritis:

class I A antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);
class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide);
some neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride). butyrophenones (droperidol, haloperidol);
others: bepridil, cisapride, difemanil, erythromycin (iv), halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, vincamine (iv), astemizole.

Increased risk of developing ventricular arrhythmias, especially arrhythmias (hypokalemia is a risk factor).

It is necessary to determine the potassium content in the blood plasma and. if necessary, adjust it before starting combination therapy with indapamide and the above drugs. It is necessary to monitor the patient’s clinical condition, monitor the level of electrolytes in the blood plasma, and ECG indicators.

In patients with hypokalemia, drugs that do not cause ari should be used.

- Systemic nonsteroidal anti-inflammatory drugs, including selective cyclooxygenase-2 (COX-2) inhibitors, high doses of acetylsalicylic acid (≥ 3 g/day):

The antihypertensive effect of indapamide may be reduced. There is a risk of developing acute renal failure due to a decrease in glomerular filtration rate. Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of therapy.

— Angiotensin-converting enzyme (ACE) inhibitors:

Prescribing ACE inhibitors to patients with low sodium levels in the blood (especially patients with renal artery stenosis) is accompanied by a risk of sudden arterial hypotension and/or acute renal failure.

Patients with arterial hypertension and, possibly, a decrease in the content of sodium ions in the blood plasma due to diuretics should:

- 3 days before starting therapy with an ACE inhibitor, stop taking the diuretic. In the future, if necessary, the diuretic can be resumed;

- or start ACE inhibitor therapy with low doses, followed by a gradual increase in dose if necessary.

In chronic heart failure, therapy with ACE inhibitors should be started with low doses, with a possible preliminary reduction in the doses of diuretics.

In all cases, in the first week of taking ACE inhibitors in patients, it is necessary to monitor renal function (plasma creatinine content).

- Other drugs that can cause hypokalemia: amphotericin B (iv), gluco- and mineralocorticosteroids for systemic use, tetracosactide, laxatives that stimulate intestinal motility:

Increased risk of hypokalemia (additive effect). Constant monitoring of potassium concentration in the blood plasma and, if necessary, its correction is necessary. It is recommended to use laxatives that do not stimulate intestinal motility.

- Baclofen:

There is an increase in the hypotensive effect. Patients need to compensate for fluid loss and carefully monitor renal function at the beginning of treatment.

— Cardiac glycosides:

Hypokalemia enhances the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, the content of potassium in the blood plasma, ECG parameters should be monitored and, if necessary, therapy should be adjusted.

Drug combinations requiring attention

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.

Clinical efficacy of indapamide in patients with hypertension

Hypertension (HD) is one of the leading causes of disability and mortality. A prolonged increase in blood pressure (BP) leads to target organ damage and the development of cardiovascular complications (heart failure, myocardial infarction, cerebral stroke and renal failure) [2, 3, 8].

Drugs for the treatment and prevention of complications of hypertension should have high therapeutic efficacy, a long-lasting antihypertensive effect throughout the day, and the absence of metabolic side effects [3, 4, 8].

The listed requirements are fully met by the drug belonging to the second generation of thiazide and thiazide-like diuretics, indapamide

. The mechanism of its antihypertensive action is associated with inhibition of sodium reabsorption in the distal convoluted tubules and the development of peripheral vasodilation [6]. Unlike hydrochlorothiazide, indapamide does not affect lipid and carbohydrate metabolism [7, 9]. One of the advantages of the drug is the ability to reduce the mass of hypertrophied left ventricular myocardium [5].

Indapamide has high bioavailability (90–95%) and a long half-life (15–25 hours), which allows for a stable antihypertensive effect throughout the day [4].

The purpose of the study conducted in our clinic was to evaluate the effectiveness and safety of indapamide under conditions of 24-hour blood pressure monitoring (ABPM), studying central hemodynamics under the control of a number of parameters of the biochemical spectrum of blood.

The study included 30 patients (12 men and 18 women) with stage I and II hypertension (according to WHO classification). The average age of the group was 47.1±11.5 years, the duration of the disease was 8.0±7.05 years. 10 patients had mild and 20 had moderate arterial hypertension (AH). Patients with symptomatic hypertension, unstable angina, previous myocardial infarction or acute cerebrovascular accident in the last 6 months, a history of liver and kidney diseases, and intolerance to sulfonamides were excluded from the study. The duration of observation was 8 weeks.

After an introductory period, during which patients did not receive antihypertensive therapy, indapamide (Hemofarm, Yugoslavia) was prescribed at a daily dose of 2.5 mg, once in the morning. If monotherapy was ineffective for 1 month, enalapril (Hemofarm, Yugoslavia) was added at a daily dose of 5–20 mg. At baseline and after 8 weeks of treatment, antihypertensive efficacy using ABPM, the effect on central hemodynamic parameters, and levels of electrolytes and blood lipids were assessed in all patients.

ABPM was carried out using a portable recorder ABRM-04 from Meditech (Hungary), which records blood pressure and heart rate during the decompression phase using the oscillometric method. Measurements began at 9–10 am. The intervals between blood pressure and heart rate measurements were 15 minutes during the day and 30 minutes at night. Based on ABPM data, we analyzed the average indicators of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate during periods of wakefulness, sleep and for the day as a whole, standard deviation to assess the variability of blood pressure and heart rate; degree of nocturnal reduction in blood pressure (SNS – percentage of reduction in blood pressure at night); percentage of blood pressure measurements exceeding the upper limit of normal in the total number of registrations; variability index. Blood pressure levels below 140/90 mmHg are considered normal. Art. during the day and below 120/70 mm Hg. Art. at night. Central hemodynamics were studied using an Acuson apparatus (USA).

Results and discussion

Before starting treatment, patients complained of headache (63%), dizziness (37%), pain in the heart of various types (27%), decreased performance (50%). 23% of patients had no complaints. According to ABPM data (Table 1), there was an increase in the average daytime, average nighttime and average daily values of SBP and DBP. The proportion of measurements that exceeded the norm, as well as the variability index, exceeded the permissible normative values, which indicated an increase in hypertensive load. The degree of nocturnal decrease (NNR) for SBP was 10.0±6.0%, for DBP – 13.0±7.5%, which corresponds to the “dipper” group. Initially, indicators of central hemodynamics (Table 2) such as average blood pressure per day and total peripheral vascular resistance (TPVR) were significantly increased.

After 8 weeks of therapy, clear positive dynamics were noted in the patients’ condition. The general well-being of the patients improved, dizziness decreased or disappeared (in 82%), headaches (in 58%), cardialgia (in 100%), and performance increased (in 80%). All patients had good tolerability of treatment, there were no side effects.

When assessing the data obtained, normalization of DBP (decrease to 90 mm Hg or lower) was considered a good result of treatment; a satisfactory result was a decrease in DBP by 10 mm Hg. Art. and more (but not to normal values), unsatisfactory - a decrease in DBP by less than 10 mm Hg. Art. or increased blood pressure. In 16 patients receiving monotherapy with indapamide, the antihypertensive result was assessed as good, in 2 patients - as satisfactory. Thus, 60% of patients achieved an effect during treatment with indapamide, which corresponds to the available literature data on the effectiveness of monotherapy [8].

There was a significant decrease in SBP per day, day, night by 14.5, 14.9 and 18 mm Hg. Art., respectively. Average daily, daytime, and nighttime DBP decreased by 8.8, 8.9, and 14.3 mmHg, respectively. Art. A significant decrease in the blood pressure variability index was revealed. Particularly noteworthy is the decrease in the absolute value of DBP and the DBP variability index, since changes in these indicators correlate with target organ damage [10]. During treatment, an unreliable increase in the SNS was noted, not exceeding 20%. The above indicates that a single dose of indapamide 2.5 mg is sufficient to maintain normal blood pressure throughout the day without affecting the physiological circadian rhythm of blood pressure.

When analyzing central hemodynamics during monotherapy with indapamide, a significant decrease in average blood pressure per day (p <0.01) and total peripheral resistance (p <0.05) was revealed, which largely explains the predominant effect of indapamide on DBP (Table 2). The dynamics of shock and cardio indices were statistically insignificant.

Twelve patients received combination therapy (indapamide 2.5 mg/day + enalapril 5–20 mg/day). At the same time, there was a significant decrease in SBP and DBP per day, day and night (Table 1), and the BP variability index. SNS increased slightly within the “dipper” group, that is, there was also no change in the circadian rhythm of blood pressure. According to echocardiography, there was a significant decrease in average blood pressure per day by 7.2% (p<0.01), peripheral vascular resistance by 13.3% (p<0.05), other indicators changed unreliably (Table 2). In 8 patients receiving combination therapy with indapamide and enalapril, the antihypertensive result was assessed as good, in 2 patients as satisfactory, in 2 patients as unsatisfactory, and therefore required the addition of verapamil at a dose of 120 mg per day. After 8 weeks of indapamide therapy, an insignificant decrease in the levels of sodium (from 142.4±2.9 to 140.4±2.3 mmol/l) and potassium (from 4.4±0.4 to 3.96±0.3) was noted mmol/l) in blood serum. Not a single patient had electrolyte levels (and, most importantly, potassium) that dropped below normal values. There were also no significant changes in the content of cholesterol and triglycerides compared to the initial level.

conclusions

1. Indapamide is a highly effective antihypertensive drug for the treatment of patients with mild and moderate forms of hypertension.

2. Considering the effect of indapamide on the peripheral vascular resistance, the drug can be prescribed primarily for diastolic hypertension.

3. The metabolic inertness of indapamide, unlike thiazides, makes it possible to recommend it to patients with hypertension in combination with metabolic disorders.

4. Adding enalapril to indapamide (if monotherapy is insufficiently effective) allows you to achieve the target blood pressure level.

Indapamide -

Indapamide (trade name)

(Hemofarm)
Literature:
1. Bulkina O.S., Dobrovolsky A.B., Britareva V.V., Marenich A.V., Karpov Yu.A. Ross. cardiol. magazine 1999; 1:39–42.

2. Gogin E.E. Hypertonic disease. M.; 1997.

3. Makolkin V.I., Podzolkov V.I. Hypertonic disease. – M.; 2000.

4. Sidorenko B.A., Preobrazhensky D.V. Diagnosis and treatment of arterial hypertension. Part two. Diuretics. M.; 2000.

5. Campbell DB, Brackman FJ Clin. Pharmacol. 1991; 31: 751–757.

6. Campbell DB, Moore R. Am. J. Hypertens. 1981; 57: 7–17.

7. FuJii S., Kaku K., Andou S., Nakayama H. et al. Clin. Ther. 1993; 15:6.

8. Hanson L., Hedner T. Hypertension Manual. 3rd ed., 2000.

9. Weidmann P., M. De Courten, P. Ferrari, Lorenz Bohlen. J. Cardiovasc. Pharmacol. 1993; 22(Suppl. 6): 98–105.

10. White WB, Dey HM, Schulman P. Am. Heart J 1989; 118:782–795.

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.

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.

Instructions for use INDAPAMIDE PHARMLAND

In patients with hepatic impairment, thiazide-like diuretics may accelerate the development of hepatic encephalopathy. If symptoms of hepatic encephalopathy occur, indapamide should be discontinued immediately.

Water and electrolyte balance

Plasma sodium level:

Before starting treatment with the drug, and then regularly it is necessary to monitor the concentration of sodium in the serum. Any diuretic treatment can lead to low sodium levels with very serious consequences. A decrease in plasma sodium may initially be asymptomatic, so regular monitoring of sodium levels is required. In elderly people or in patients with cirrhosis of the liver, these studies should be performed more often.

Plasma potassium content:

Serum potassium should be monitored regularly during treatment. A decrease in potassium levels with possible subsequent hypokalemia is the main risk of taking thiazide and other diuretics based on it. Prevention of the risk of hypokalemia (<3.4 mmol/L) should be carried out in certain high-risk populations, for example, the elderly, people who are malnourished and/or taking multiple medications at the same time, cirrhotic patients with edema and ascites, patients with coronary vascular disease and hearts. In this situation, hypokalemia increases the cardiac toxicity of digitalis drugs and the risk of arrhythmias. Patients with a prolonged QT interval are also at risk, regardless of whether it is congenital or iatrogenic. Hypokalemia, as well as bradycardia, are a predisposing factor for the occurrence of severe arrhythmias, in particular the potentially fatal atrial flutter-fibrillation. In all of the above situations, more frequent monitoring of plasma potassium levels is necessary. The first measurement of plasma potassium should be performed in the first week of starting treatment. In case of hypokalemia, potassium deficiency should be compensated.

Plasma calcium content:

Thiazide and thiazide-like diuretics may reduce urinary calcium excretion, causing mild transient hypercalcemia. Severe hypercalcemia may result from unrecognized hyperparathyroidism. In this case, it is necessary to interrupt treatment and examine the patient for the function of the parathyroid glands.

Blood sugar level

In patients with diabetes mellitus, especially those with concomitant hypokalemia, it is necessary to monitor blood glucose levels.

Uric acid

Patients with hyperuricemia tend to have an increased frequency of gout attacks. If uric acid levels increase, dose adjustment is necessary.

Kidney function and diuretics

Thiazides and thiazide-like diuretic drugs are fully effective only in the case of normal renal function or only mild impairment (creatinine content below 25 mg/l, i.e. 220 mmol/l). Hypovolemia associated with fluid loss, which may occur at the beginning of diuretic treatment, leads to a decrease in glomerular filtration, which in turn causes an increase in serum urea and creatinine concentrations. Such transient functional renal failure passes without consequences in patients with normal renal function, but at the same time it can aggravate existing renal failure.

Athletes

The drug may cause false-positive anti-doping test results in athletes.

Impact on the ability to drive vehicles and machinery

While taking Indapamide Pharmland, especially at the beginning of treatment or when prescribing another antihypertensive drug for combination treatment, symptoms associated with a drop in blood pressure may occur. In such a situation, the ability to drive vehicles and maintain machinery may be impaired.