Description
Arifon Pharmacodynamics
Mechanism of action
Indapamide belongs to sulphonamide derivatives with indole ring and by its pharmacological properties is similar to thiazide diuretics, which inhibit sodium ions reabsorption in cortical segment of nephron loop. At the same time, renal excretion of sodium and chlorine ions and, to a lesser extent, potassium and magnesium ions increases, which is accompanied by increased diuresis and hypotensive effect.
Pharmacodynamic effects
In phase II and phase III clinical studies, a 24-hour hypotensive effect was demonstrated when indapamide was used as monotherapy in doses that did not have a pronounced diuretic effect.
The antihypertensive activity of indapamide is associated with improvement of elastic properties of large arteries, reduction of arteriolar and total peripheral vascular resistance.
Indapamide reduces left ventricular hypertrophy.
Thiazide and thiazide-like diuretics reach a plateau of therapeutic effect at a certain dose, while the frequency of side effects continues to increase with further increases in the drug dose. Therefore, the drug dose should not be increased if the therapeutic effect is not achieved at the recommended dose.
In short-, medium-, and long-term studies involving patients with arterial hypertension, it has been shown that indapamide
– has no effect on lipid metabolism parameters, including triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein levels;
– does not affect parameters of carbohydrate metabolism, including in patients with diabetes mellitus.
Indications
Arterial hypertension in adults.
Arterial hypertension in adults.
Contraindications
Hypersensitivity to the active substance, other sulfonamide derivatives or any of the excipients (see section “Composition”).
– Severe renal failure (creatinine clearance less than 30 ml/min).
– Severe hepatic insufficiency or hepatic encephalopathy.
– Hypokalemia.
Due to the fact that the drug contains lactose, Arifon® retard is not recommended for patients with lactose intolerance, galactosemia, glucose-galactose malabsorption.
Caution:
Impaired liver and renal function, water-electrolyte balance disorders, weakened patients or patients receiving combined therapy with other antiarrhythmic drugs (see “Interaction with other drugs”), diabetes, elevated uric acid levels, patients with prolonged QT interval, hyperparathyroidism.
Usage during pregnancy and breast-feeding:
Pregnancy .
There are currently insufficient data on the use of indapamide during pregnancy (fewer than 300 cases have been described). Prolonged use of thiazide diuretics in the third trimester of pregnancy may cause hypovolemia in the mother and reduced uteroplacental blood flow, resulting in fetoplacental ischemia and delayed fetal development. No direct or indirect effects on pregnancy have been observed in animal studies. Indapamide should be avoided during pregnancy.
Breastfeeding period
It is not known whether indapamide or its metabolites are excreted with breast milk. The newborn may develop hypersensitivity to sulfonamide derivatives and hypokalemia. Therefore, the risk to the newborn/infant cannot be excluded. Indapamide is close to thiazide diuretics, administration of which causes reduction of breast milk or even suppression of lactation. Indapamide should not be used during breastfeeding.
Fertility
Preclinical studies have shown no effect on fertility in rats of either sex. Presumably there is no effect on fertility in humans.
Hypersensitivity to the active substance, other sulfonamide derivatives or any of the excipients (see section “Composition”).
– Severe renal failure (creatinine clearance less than 30 ml/min).
– Severe hepatic insufficiency or hepatic encephalopathy.
– Hypokalemia.
Due to the fact that the drug contains lactose, Arifon® retard is not recommended for patients with lactose intolerance, galactosemia, glucose-galactose malabsorption.
Caution:
Impaired liver and renal function, water-electrolyte balance disorders, weakened patients or patients receiving combined therapy with other antiarrhythmic drugs (see “Interaction with other drugs”), diabetes, elevated uric acid levels, patients with prolonged QT interval, hyperparathyroidism.
Usage during pregnancy and breast-feeding:
Pregnancy .
There are currently insufficient data on the use of indapamide during pregnancy (fewer than 300 cases have been described). Prolonged use of thiazide diuretics in the third trimester of pregnancy may cause hypovolemia in the mother and reduced uteroplacental blood flow, resulting in fetoplacental ischemia and delayed fetal development. No direct or indirect effects on pregnancy have been observed in animal studies. Indapamide should be avoided during pregnancy.
Breastfeeding period
It is not known whether indapamide or its metabolites are excreted with breast milk. The newborn may develop hypersensitivity to sulfonamide derivatives and hypokalemia. Therefore, the risk to the newborn/infant cannot be excluded. Indapamide is close to thiazide diuretics, administration of which causes reduction of breast milk or even suppression of lactation. Indapamide should not be used during breastfeeding.
Fertility
Preclinical studies have shown no effect on fertility in rats of either sex. Presumably there is no effect on fertility in humans.
Dosage and administration
- Oral administration – 1 tablet per day, preferably in the morning; the tablet should be swallowed in whole without chewing, with water.
When treating patients with arterial hypertension, increasing of the drug dose does not increase antihypertensive effect but increases diuretic effect. - Special patient groups
Patients with renal insufficiency (see sections “Contraindications” and “Special indications”) - Indapamide is contraindicated in patients with severe renal insufficiency (CKR less than 30 ml/min). Thiazide and thiazide-like diuretics are effective only in patients with normal or mild renal function impairment.
Patients with hepatic insufficiency (see sections “Contraindications” and “Special indications”) - The drug is contraindicated in patients with severe hepatic insufficiency.
Elderly patients (see sect. “Cautionary information”)
In elderly patients, plasma creatinine concentration should be monitored with regard to age, body weight and sex. - Arifon® retard at a dose of 1.5 mg/day (1 tablet) may be administered in elderly patients with normal or mildly impaired renal function (see “Contraindications”).
Children and adolescents under 18 years of age - There are currently no data on the safety and effectiveness of Arifon® Retard in children and adolescents.
