Description
Perindopril Plus Pharmacodynamics
The medicinal product Indapamide + Perindopril is a combined preparation containing indapamide and perindopril erbumin. Pharmacological properties of the drug Indapamide + Perindopril combine the individual properties of each of its active components.
Mechanism of action
Indapamide + Perindopril
The combination of indapamide and perindopril enhances the antihypertensive effects of each.
Perindopril
Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (angiotensin-converting enzyme (ACE) inhibitor). ACE, or kininase II, is an exopeptidase that performs both the conversion of angiotensin I to the vasoconstrictor angiotensin II and the degradation of bradykinin, which has a vasodilatory effect, to an inactive heptapeptide. As a result, perindopril:
– Reduces aldosterone secretion;
– by the principle of negative feedback, it increases plasma renin activity;
– with prolonged use it reduces total peripheral vascular resistance (TPRR), which is mainly due to the effect on the vessels in the muscles and kidneys. These effects are not accompanied by retention of sodium ions and fluid or development of reflex tachycardia.
Perindopril normalizes myocardial function by reducing preload and postload.
The study of hemodynamic parameters in patients with chronic heart failure (CHF) revealed:
– decreased filling pressure in the left and right ventricles of the heart;
– decreased ROSS;
– increased cardiac output and increased cardiac index;
– increased muscle peripheral blood flow.
Indapamide
Indapamide belongs to the group of sulfonamides, with pharmacological properties similar to thiazide diuretics. Indapamide inhibits reabsorption of sodium ions in the cortical segment of the Genle loop, which leads to increased renal excretion of sodium ions, chloride and, to a lesser extent, sodium and magnesium ions, thereby increasing diuresis, and reducing blood pressure (BP).
Indications
Essential hypertension.
Contraindications
Perindopril
– Hypersensitivity to perindopril and other ACE inhibitors;
– History of angioedema (Quincke’s edema) with other ACE inhibitors (see section “Special Precautions”);
– Hereditary/ idiopathic angioedema;
– Pregnancy and breastfeeding (see section “Administration during pregnancy and breastfeeding”);
– Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or moderate or severe renal dysfunction (glomerular filtration rate (GFR) less than 60 ml/min/1.73m2 body surface area) (see sections “Pharmacodynamics” and “Interaction with other medicinal products”).
– Concomitant use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy (see section “Cautions”).
– Under 18 years of age (efficacy and safety not established).
Indapamide .
– Hypersensitivity to indapamide and other sulfonamides;
– Moderate to severe renal insufficiency (creatinine clearance (CK) less than 60 ml/min);
– Severe hepatic insufficiency;
– Hepatic encephalopathy;
– Hypokalemia;
– Concomitant use with non antiarrhythmic drugs that may cause pirouette-type polymorphic ventricular tachycardia (see section “Interaction with other medicinal products”);
– Breast-feeding period (see section “Administration during pregnancy and breast-feeding”);
– Under 18 years of age (efficacy and safety have not been established).
Indapamide + Perindopril
– Hypersensitivity to excipients included in the drug (see section “Composition”);
– Due to lack of sufficient clinical experience, the drug Indapamide + Perindopril should not be used in patients on hemodialysis or in patients with untreated decompensated heart failure;
– Under 18 years of age (efficacy and safety not established);
– Presence of lactase deficiency, galactosemia or glucose-galactose malabsorption syndrome, lactose intolerance (the drug contains lactose).
Dosage and administration
- Orally, once a day, preferably in the morning, before breakfast, with plenty of fluids.
- If possible, the drug should be started with a selection of doses of single-unit drugs. If clinically necessary, combined therapy with Indapamide + Perindopril may be prescribed immediately after monotherapy with one of the components of the drug (perindopril and indapamide).
- Doses are given for the indapamide/perindopril ratio.
- The initial dose is 1 tablet of indapamide + perindopril
- (0.625 mg/2mg) once a day. If after 1 month of taking this drug it is not possible to achieve adequate BP control, the drug dose should be increased to
- 1 tablet of Indapamide + Perindopril (1.25 mg/4 mg) once daily.
- If necessary, to achieve a more pronounced hypotensive effect, the drug dose may be increased to the maximum daily dose of Indapamide + Perindopril – 1 tablet (2.5 mg/8 mg) once daily.
- Elderly patients
- The initial dose is 1 tablet of 0.625 mg/2 mg of Indapamide + Perindopril once daily.
- The drug therapy should be started under control of renal function and BP.
- Patients with impaired renal function
- Indapamide + Perindopril is contraindicated in patients with severe renal impairment (CK values less than 30 ml/min) (see section “Contraindications”).
- In patients with moderately severe renal impairment
- (IQ 30-60 ml/min), it is recommended to start therapy with the required doses (in monotherapy) of Indapamide + Perindopril; maximum daily dose of Indapamide + Perindopril is 1.25 mg/4 mg.
- Patients with a CK of 60 ml/min or more do not require dose adjustment. Serum creatinine and potassium concentrations should be monitored regularly during therapy.
- Patients with liver dysfunction
- The drug is contraindicated in patients with severe hepatic insufficiency (see section “Contraindications”).
- Dosage adjustment is not required in moderately severe hepatic insufficiency.
- Children and adolescents
- Indapamide + Perindopril should not be used in children and adolescents under 18 years of age, since data on efficacy and safety are insufficient.
