Indapamide

Pharmacological properties

Pharmacodynamics

Mechanism of action. Indapamide is a sulfonamide diuretic with an indole ring, which is pharmacologically similar to thiazide diuretics and is used to treat hypertension.

Indapamide acts at the level of the kidneys and blood vessels.

Indapamide inhibits sodium reabsorption in the cortical segment of the kidney. This increases the excretion of sodium and chloride with urine and, to a lesser extent, the excretion of potassium and magnesium, thereby increasing diuresis.

Pharmacodynamic effects. Clinical trials of the II – III phase using indapamide in monotherapy have demonstrated that the antihypertensive effect of indapamide lasts for 24 hours. The diuretic effect was moderate. The antihypertensive effect of indapamide is associated with an improvement in the elasticity of arteries and a decrease in the resistance of arterioles and OPSS.

Indapamide reduces left ventricular hypertrophy.

If the recommended dose is exceeded, the therapeutic effect of thiazides and thiazide-like diuretics does not increase, while the number of adverse events increases. If the treatment is not effective enough, increasing the dose is not recommended.

As shown in studies of different durations (short, medium and long) involving patients with hypertension, indapamide does not affect metabolism:

• lipids (TG, LDL cholesterol and HDL cholesterol);
• carbohydrates, even in patients with diabetes and hypertension.

Indapamide acts at the vascular level by:

• decrease in the contractility of vascular smooth muscle, which is associated with changes in the transmembrane exchange of ions (mainly calcium);
• stimulation of prostaglandin synthesis PGE₂ and prostacyclin PGI₂ (vasodilator and platelet aggregation inhibitor).

Pharmacokinetics The active substance - 1.5 mg of indapamide is in a tablet of prolonged action, created on the basis of the matrix. The distribution of indapamide in the matrix system ensures its uniform release from the tablet.

Absorption. The released indapamide fraction is rapidly and completely absorbed in the digestive tract. Eating slightly increases the rate of absorption, but does not affect the amount of drug that is absorbed.

C_max in a blood plasma after a single dose is achieved after about 12 hours, further use of the drug reduces fluctuations in the level of indapamide in the blood plasma in the interdose interval. There are intraindividual vibrations.

Distribution. Linking blood plasma proteins - 79%. T_½ is from 14 to 24 hours (on average - 18 hours). A stable concentration level is reached after 7 days. Regular use does not cause cumulation.

Indapamide is excreted in urine (70% of the dose) and feces (22%) as inactive metabolites.

High risk patients. In patients with renal failure, the pharmacokinetic parameters do not change.

Indications

Arifon retard is indicated for essential hypertension in adults.

Application

For oral use: 1 tablet per day, preferably in the morning. the tablet should be swallowed whole, without chewing, washed down with water.

The use of the drug in higher doses does not increase the antihypertensive effect, but the diuretic effect increases.

Special patient groups

Renal failure (see SPECIAL INSTRUCTIONS and CONTRAINDICATIONS). In patients with severe renal failure (creatinine clearance of 30 ml / min), the use of the drug is contraindicated. Thiazide and thiazide-like diuretics are most effective if renal function is not impaired or if the impairment is minor.

Old age (see SPECIAL INSTRUCTIONS). In elderly patients, plasma creatinine should be at a level corresponding to age, body weight and gender. Elderly patients Arifon Retard can be prescribed if kidney function is not impaired or if the impairment is minor.

Patients with impaired liver function (see SPECIAL INSTRUCTIONS and CONTRAINDICATIONS).In case of severe dysfunction of the liver, drug treatment is contraindicated.

Children. The safety and effectiveness of the drug Arifon Retard in children have not been established. No data available.

Contraindications

Hypersensitivity to the active substance, to other sulfonamides or any auxiliary components of the drug; severe renal failure; hepatic encephalopathy and severe impaired liver function; hypokalemia.

Side effects

Most often, the occurrence of such adverse reactions was reported: hypersensitivity reactions, mainly dermatological, in patients prone to the development of allergic and asthmatic reactions, and maculopapular rash.

During clinical trials, hypokalemia (potassium in the blood plasma of 3.4 mmol / L) was observed in 10% of patients, in 4% of cases the level of potassium decreased to 3.2 mmol / L after 4-6 weeks of treatment. After 12 weeks of therapy, the average decrease in potassium in the blood plasma was 0.23 mmol / L.

Most of the undesirable effects, both clinical and laboratory ones, are dose-dependent.

During treatment with indapamide, the following side effects were observed, listed below, with such a frequency of occurrence: very often (≥1 / 10), often (≥1 / 100, 1/10), infrequently (≥1 / 1000, 1/100), rarely (≥1 / 10,000, 1/1000), very rarely (≥1 / 100,000, 1/10 000), the frequency is unknown (cannot be determined according to the available information).

special instructions

In patients with impaired liver function, the use of thiazide-like diuretics can cause the development of hepatic encephalopathy, especially in cases of electrolyte imbalance. in this case, the use of diuretics should be stopped immediately.

Photosensitivity. Cases of photosensitivity reactions have been reported in patients taking thiazide and thiazide-like diuretics (see ADVERSE EFFECTS). If such reactions occur, diuretic treatment is recommended to be discontinued. If necessary, re-appointment of diuretics should protect vulnerable parts of the body from the sun or sources of artificial ultraviolet radiation.

Excipients. The drug contains lactose, therefore, it should not be prescribed to patients with congenital galactose intolerance, glucose and galactose malabsorption syndrome, Lapp lactase deficiency.

The balance of water and electrolytes

Sodium in blood plasma. It is necessary to control the level of sodium in the blood plasma before starting therapy and in the future - regularly during treatment. Decreased plasma sodium levels may be asymptomatic at first, so regular monitoring is necessary. Monitoring sodium levels should be carried out more often in elderly patients and in patients with cirrhosis. Any diuretic can cause hyponatremia, which sometimes has serious consequences. Hyponatremia with hypovolemia can lead to dehydration and orthostatic hypotension; concomitant loss of chlorine ions can cause secondary compensatory metabolic alkalosis (the frequency and severity of this phenomenon is low).

Potassium in the blood plasma. A decrease in the level of potassium in the blood plasma with the occurrence of hypokalemia is the main risk when using thiazide and thiazide-like diuretics. The likelihood of developing hypokalemia (3.4 mmol / L) should be prevented in certain categories of high-risk patients, such as the elderly, patients who are undernourished and / or patients who take a lot of medications, patients with cirrhosis, accompanied by edema and ascites, patients with ischemic heart disease and patients with heart failure. In such cases, hypokalemia increases cardiotoxicity of cardiac glycosides and the risk of arrhythmia.

Patients with an extended Q – T interval of congenital or iatrogenic origin are also at risk. Hypokalemia, like bradycardia, can contribute to the development of severe cardiac arrhythmias, in particular paroxysmal ventricular tachycardia of the pirouette type, which can lead to death.

In all of the above cases, frequent monitoring of potassium levels in the blood is necessary. The first analysis should be carried out during the 1st week of treatment. If hypokalemia is detected, it should be corrected.

Plasma calcium. Thiazide and thiazide-like diuretics can reduce urinary calcium excretion and lead to a slight and temporary increase in plasma calcium levels. Severe hypercalcemia may be a consequence of pre