Instructions for Perindopress duo tablets 8mg/2.5mg No. 30
Composition
active ingredients: perindopril, indapamide;
Perindopres® Duo, 4 mg/1.25 mg tablets
1 tablet contains perindopril tert-butylamine 4 mg (corresponding to 3.338 mg perindopril) and indapamide 1.25 mg.
Perindopres® Duo, 8 mg/2.5 mg tablets
1 tablet contains perindopril tert-butylamine 8 mg (corresponding to 6.676 mg perindopril) and indapamide 2.5 mg.
Excipients: lactose monohydrate, microcrystalline cellulose, crospovidone, colloidal hydrophobic silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: tablets of white or almost white color, flat-cylindrical shape, with a bevel.
Pharmacotherapeutic group
Combinations of angiotensin-converting enzyme (ACE) inhibitors. Perindopril and diuretics. ATX code C09B A04.
Pharmacological properties
Pharmacodynamics.
Perindopril® Duo is a combination of the ACE inhibitor perindopril tert-butylamine and the sulfonamide diuretic indapamide. Its pharmacological action is due to the properties of each component (perindopril and indapamide) and their additive synergism.
Mechanism of action
Perindopril is an ACE inhibitor that converts angiotensin I to angiotensin II (a vasoconstrictor substance), additionally stimulates the secretion of aldosterone by the adrenal cortex and the breakdown of bradykinin (a vasodilating substance) to inactive heptapeptides. As a result of ACE inhibition, a decrease in aldosterone secretion occurs, an increase in renin activity in the blood plasma without the negative effect of aldosterone, a decrease in total peripheral vascular resistance due to the predominant effect on the vessels of the muscles and kidneys. At the same time, there is no water and salt retention or reflex tachycardia, even with long-term treatment. In addition, perindopril reduces blood pressure (BP) in patients with normal and low levels of renin in the blood plasma. Perindopril acts through its active metabolite perindoprilat. Other metabolites are inactive. Perindopril facilitates the work of the heart due to its vasodilator effect on the veins (possibly due to changes in prostaglandin metabolism) - reducing preload and by reducing total peripheral vascular resistance - reducing afterload on the heart. Studies conducted with the participation of patients with heart failure have shown that the use of perindopril leads to a decrease in the filling pressure of the left and right ventricles, a decrease in total peripheral vascular resistance, an increase in cardiac output and an improvement in the cardiac index, an increase in regional blood flow in the muscles. The indicators of physical exercise tests are improved.
Indapamide is a sulfonamide derivative with an indole ring, pharmacologically related to the thiazide diuretic group. Indapamide inhibits sodium reabsorption in the cortical segment of the kidneys. This increases the urinary excretion of sodium and chloride and, to a lesser extent, the excretion of potassium and magnesium, thereby increasing diuresis. This mechanism provides an antihypertensive effect.
Pharmacodynamic effects
The drug Perindopril/Indapamide has a dose-dependent antihypertensive effect on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients of all ages with arterial hypertension in both the supine and standing positions.
Indapamide. When used as monotherapy, indapamide has an antihypertensive effect that lasts 24 hours. This effect is manifested at doses in which the diuretic properties are minimal. The antihypertensive effect of indapamide is proportional to the improvement of arterial elasticity and the reduction of arteriolar resistance and total peripheral vascular resistance. Indapamide reduces left ventricular hypertrophy. When the dose is exceeded, the antihypertensive effect of thiazide and thiazide-like diuretics reaches a plateau, while the number of undesirable effects increases. If the treatment is not effective enough, the dose of the drug should not be increased. In studies of various durations (short, medium and long) involving patients with arterial hypertension, indapamide does not affect lipid metabolism (triglycerides, low and high density lipoproteins) and does not affect carbohydrate metabolism, even in patients with arterial hypertension and diabetes mellitus.
Pharmacokinetics.
The pharmacokinetic properties of perindopril and indapamide when used in combination do not differ from the properties of these components when used separately.
Pharmacokinetic properties of perindopril
Absorption and bioavailability. After oral administration, perindopril is rapidly absorbed, with peak plasma concentrations occurring within 1 hour. The plasma half-life of perindopril is 1 hour. Since food intake reduces the conversion of perindopril to perindoprilat and, consequently, its bioavailability, perindopril tert-butylamine should be taken orally in a single daily dose in the morning before meals.
Distribution: The volume of distribution of unbound perindoprilat is approximately 0.2 l/kg. The binding of perindoprilat to plasma proteins is 20%, mainly to ACE, and is dose-dependent.
Biotransformation. Perindopril is a prodrug. Thus, 27% of the dose of perindopril enters the bloodstream in the form of the active metabolite perindoprilat. In addition to the active perindoprilat, perindopril forms 5 more inactive metabolites. The maximum concentration of perindoprilat in the blood plasma is reached after 3–4 hours.
Excretion: Perindoprilat is excreted in the urine, with a terminal half-life of the unbound fraction of approximately 17 hours. Steady state is reached within 4 days.
Linearity/non-linearity: A linear relationship between the dose of perindopril and its plasma concentration has been demonstrated.
Special categories of patients
Elderly patients: The elimination of perindoprilat is reduced in elderly patients and in those with cardiac or renal insufficiency.
Renal impairment: For patients with renal insufficiency, the dose should be adapted depending on the degree of renal impairment (creatinine clearance).
Need for dialysis. The dialysis clearance of perindoprilat is 70 ml/min.
Cirrhosis of the liver. The kinetics of perindopril are altered in patients with cirrhosis of the liver: the hepatic clearance of the parent molecule is halved, but the amount of perindoprilat formed is not reduced (see sections "Special warnings and precautions for use" and "Dosage and administration").
Pharmacokinetic properties of indapamide
Absorption: Indapamide is rapidly and completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached approximately 1 hour after oral administration.
Distribution: Plasma protein binding is 79%.
Biotransformation and elimination. The elimination half-life is 14–24 hours (average 18 hours). Repeated administration does not lead to accumulation. Excretion occurs mainly in the urine (70% of the dose) and feces (22%) in the form of inactive metabolites.
Special categories of patients
Renal impairment: Pharmacokinetic parameters are not altered in patients with renal insufficiency.
Indication
Essential hypertension.
Contraindication
Related to perindopril:
hypersensitivity to perindopril or any other ACE inhibitor;
a history of angioedema (Quincke's edema) associated with previous treatment with ACE inhibitors (see section "Special warnings and precautions for use");
congenital or idiopathic angioedema;
pregnancy or planning a pregnancy (see section "Use during pregnancy or breastfeeding");
simultaneous use with drugs containing aliskiren in patients with impaired renal function (glomerular filtration rate < 60 ml/min/1.73 m2) or with diabetes mellitus (see section "Interaction with other medicinal products and other types of interactions");
simultaneous use with sacubitril/valsartan (see sections “Interaction with other medicinal products and other types of interactions” and “Special precautions for use”);
extracorporeal treatments that result in blood coming into contact with negatively charged surfaces (see section “Interaction with other medicinal products and other types of interactions”);
significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney (see section "Special warnings and precautions for use").
Related to indapamide:
hypersensitivity to indapamide or to any other sulfonamides;
severe and moderate renal impairment (creatinine clearance < 60 ml/min) for the 8 mg/2.5 mg dosage;
hepatic encephalopathy;
severe liver dysfunction;
hypokalemia;
As a general rule, this medicinal product should not be administered in combination with non-antiarrhythmic drugs that may cause the development of paroxysmal ventricular tachycardia of the "pirouette" type;
breastfeeding period (see section "Use during pregnancy or breastfeeding").
Related to the drug Perindopress® Duo:
hypersensitivity to any excipient of the drug.
Due to the lack of sufficient clinical experience, Perindopril should not be used:
patients on hemodialysis;
patients with untreated decompensated heart failure.
Interaction with other medicinal products and other types of interactions
Interactions common to perindopril and indapamide
Concomitant use is not recommended.
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant use of lithium and ACE inhibitors. The concomitant use of perindopril with indapamide and lithium is not recommended, but if necessary, serum lithium concentrations should be carefully monitored (see section 4.4).
Concomitant use requiring special attention
Baclofen. Increased antihypertensive effect. Blood pressure should be monitored and the dose of the antihypertensive agent adjusted if necessary.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid at a dose of ≥ 3 g/day. With the simultaneous use of ACE inhibitors and NSAIDs, such as acetylsalicylic acid at anti-inflammatory doses, COX-2 inhibitors and non-selective NSAIDs, a weakening of the antihypertensive effect is possible. The simultaneous use of ACE inhibitors and NSAIDs may lead to an increased risk of renal dysfunction, including the development of acute renal failure, and an increase in serum potassium, especially in patients with impaired renal function. Such a combination should be prescribed with caution, especially in elderly patients. Patients should be rehydrated before starting treatment and renal function should be monitored at the beginning and during combination therapy.
Concomitant use requiring attention
Imipramine-like (tricyclic) antidepressants, neuroleptics. Enhance the antihypertensive effect and increase the risk of developing orthostatic hypotension (additive effect).
Interactions related to perindopril
Clinical trial data suggest that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with an increased incidence of adverse reactions such as hypotension, hyperkalaemia and renal impairment (including acute renal failure) compared to the use of a single RAAS-acting agent (see sections 5.1, 5.3 and 4.4).
Drugs that cause hyperkalemia. Some drugs or therapeutic classes of drugs, such as aliskiren, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, heparins, immunosuppressive agents (such as cyclosporine or tacrolimus, trimethoprim), may cause hyperkalemia. The combination of these drugs increases the risk of hyperkalemia.
Concomitant use is contraindicated (see Contraindications section).
Aliskiren: Patients with diabetes mellitus or renal insufficiency are at increased risk of hyperkalemia, renal dysfunction, and cardiovascular morbidity and mortality.
Extracorporeal therapies: Extracorporeal therapies that result in contact of blood with negatively charged surfaces, such as dialysis or hemofiltration using certain membranes with high hydraulic permeability (e.g. polyacrylonitrile) and low-density lipoprotein (LDL) apheresis using dextran sulfate, due to an increased risk of severe anaphylactoid reactions (see section 4.3). If such treatments are necessary, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.
Sacubitril/valsartan. Concomitant use of perindopril with sacubitril/valsartan is contraindicated because concomitant inhibition of neprilysin and ACE may increase the risk of angioedema. Sacubitril/valsartan should not be initiated earlier than 36 hours after the last dose of perindopril. Perindopril therapy should not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.4).
Aliskiren: In all other patient groups, as well as in patients with diabetes mellitus or renal impairment, the risk of hyperkalemia, renal impairment and cardiovascular morbidity and mortality is increased (see section 4.4).
Concomitant therapy with an ACE inhibitor and an angiotensin receptor blocker. In patients with established atherosclerosis, heart failure, or diabetes mellitus with target organ damage, concomitant therapy with an ACE inhibitor and an angiotensin receptor blocker has been reported to be associated with an increased incidence of hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal failure) compared with the use of a single RAAS-acting agent. Dual blockade (i.e., the combination of an ACE inhibitor and an angiotensin II receptor antagonist) should be considered only in selected cases and with careful monitoring of renal function, blood potassium, and blood pressure (see section 4.4).
Estramustine: There is a risk of increased incidence of adverse reactions such as angioedema.
Potassium-sparing diuretics (e.g. triamterene, amiloride), potassium (salts). There is a risk of hyperkalemia (potentially fatal), especially in patients with impaired renal function (additive hyperkalemic effect). The combination of perindopril with the above-mentioned drugs is not recommended (see section "Special warnings and precautions for use"). If concomitant use of these drugs is nevertheless indicated, they should be used with caution, with frequent monitoring of serum potassium. Information on the use of spironolactone in patients with heart failure is provided in the section "Concomitant use requiring special attention".
Co-trimoxazole (trimethoprim/sulfamethoxazole): Patients receiving co-trimoxazole may be at increased risk of developing hyperkalemia (see section 4.4).
Concomitant use requiring special attention
Antidiabetic agents (insulin, oral hypoglycemic agents). Epidemiological studies suggest that the concomitant use of ACE inhibitors and antidiabetic agents (insulins, oral hypoglycemic agents) may lead to an increased blood sugar-lowering effect with a risk of hypoglycemia. This phenomenon is more likely to occur during the first weeks of combined treatment and in patients with impaired renal function.
Diuretics. In patients taking diuretics, especially if they are water and sodium depleted, excessive blood pressure may occur after initiating therapy with an ACE inhibitor. The likelihood of hypotensive effects can be reduced by discontinuing the diuretic, increasing the circulating blood volume, or increasing salt intake before initiating therapy with perindopril, which should be initiated at a low dose and titrated. In hypertensive patients in whom previous diuretic therapy may have caused water/sodium depletion, the diuretic should be discontinued before initiating therapy with an ACE inhibitor (in which case the diuretic may be reinstituted over time) or the ACE inhibitor should be initiated at a low dose and titrated. In patients with congestive heart failure receiving a diuretic, treatment with an ACE inhibitor should be initiated at the lowest dose, possibly after a reduction in the diuretic dose. In all cases, renal function (creatinine levels) should be monitored during the first few weeks of ACE inhibitor therapy.
Potassium-sparing diuretics (eplerenone, spironolactone). When eplerenone or spironolactone at doses of 12.5 mg to 50 mg per day are used concomitantly with low-dose ACE inhibitors in patients with heart failure of New York Heart Association (NYHA) functional classes II–IV and an ejection fraction < 40%, who have previously received ACE inhibitors and loop diuretics, there is a risk of hyperkalemia, potentially fatal, especially if the recommendations for the appointment of such a combination are not followed. Before starting the use of such a combination, it is necessary to ensure the absence of hyperkalemia and impaired renal function. It is recommended to carefully monitor potassium and creatinine weekly during the first month of treatment and monthly thereafter.
Racecadotril: ACE inhibitors (e.g. perindopril) are known to cause angioedema. This risk may be increased when used concomitantly with racecadotril (a medicine used to treat acute diarrhoea).
mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus): Patients receiving concomitant mTOR inhibitors may be at increased risk of developing angioedema (see section 4.4).
Concomitant use requiring attention
Allopurinol, cytostatics, immunosuppressive agents, systemic corticosteroids or procainamide. Concomitant use with ACE inhibitors may lead to an increased risk of leukopenia (see section "Special warnings and precautions for use").
Anesthetics: ACE inhibitors may enhance the hypotensive effect of some anesthetics (see section "Special warnings and precautions for use").
Gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin). When used simultaneously with an ACE inhibitor, the risk of angioedema increases due to inhibition of dipeptidyl peptidase-IV (DPP-IV) activity by the gliptin.
Sympathomimetics: Sympathomimetics may attenuate the antihypertensive effect of ACE inhibitors.
Gold preparations: In patients treated with injectable gold preparations (sodium aurothiomalate) and concomitant use of an ACE inhibitor, including perindopril, nitritoid reactions (symptoms: facial flushing, nausea, vomiting and hypotension) have been reported rarely.
Interactions related to indapamide
Concomitant use requiring special attention
Drugs that may induce paroxysmal ventricular tachycardia of the "pirouette" type. Due to the risk of hypokalemia, indapamide should be prescribed with caution in combination with drugs that may induce paroxysmal ventricular tachycardia of the "pirouette" type, such as class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide); class III antiarrhythmic drugs (amiodarone, dofetilide, ibutilide, bretylium, sotalol); some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other neuroleptics (pimozide), other drugs such as bepridil, cisapride, diphemanil, erythromycin for intravenous use, halofantrine, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine for intravenous use, methadone, astemizole, terfenadine. It is necessary to prevent a decrease in the level of potassium in the blood plasma and, if necessary, correct it, as well as monitor the QT interval.
Drugs that lower blood potassium. Amphotericin B for intravenous use, glucocorticoids and mineralocorticoids (systemic), tetracosactide, laxatives that stimulate peristalsis increase the risk of a decrease in serum potassium (additive effect). It is necessary to monitor the potassium content in the blood plasma and correct it if necessary, especially during concomitant treatment with digitalis preparations. Laxatives that do not stimulate peristalsis should be used.
Digitalis preparations. Hypokalemia and/or hypomagnesemia increase the toxic effects of digitalis preparations. It is necessary to monitor the level of potassium, magnesium in the blood plasma and ECG, and, if necessary, review the therapy.
Allopurinol: Concomitant use with indapamide may lead to an increased incidence of hypersensitivity reactions to allopurinol.
Concomitant use requiring attention
Potassium-sparing diuretics (amiloride, spironolactone, triamterene). Although this combination is appropriate in some patients, hypokalemia or hyperkalemia may occur (especially in patients with renal insufficiency or diabetes mellitus). Plasma potassium levels should be monitored, ECG monitoring should be performed, and therapy should be reviewed if necessary.
Metformin: May cause lactic acidosis due to functional renal failure associated with diuretics, especially loop diuretics. Metformin should not be used if plasma creatinine levels exceed 15 mg/L (135 μmol/L) in men and 12 mg/L (110 μmol/L) in women.
Iodine contrast media. In case of dehydration caused by the use of diuretics, the risk of developing acute renal failure increases, especially when using large doses of iodocontrast media. Before using iodocontrast media, it is necessary to restore water balance.
Calcium (salts). There is a risk of increased calcium levels in the blood due to reduced urinary excretion.
Cyclosporine, tacrolimus: There is a risk of an increase in blood creatinine without a change in circulating cyclosporine concentration, even in the absence of water and sodium depletion.
Corticosteroids, tetracosactide (systemic action). Reduce the antihypertensive effect (water and sodium retention under the influence of corticosteroids).
Application features
Special precautions
Special precautions common to perindopril and indapamide
Lithium: The concomitant use of lithium and the combination of perindopril/indapamide is generally not recommended (see section 4.5).
Dual blockade of the RAAS. There is evidence that the concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Therefore, the use of dual blockade of the RAAS due to the concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see section 4.5). If dual blockade of the RAAS is considered absolutely necessary, it should be carried out only under specialist supervision and with frequent and careful monitoring of renal function, electrolytes and blood pressure. ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Potassium-sparing medicinal products, potassium-containing salt supplements or salt substitutes: The combination of perindopril and potassium-sparing medicinal products, potassium-containing salt supplements or salt substitutes is generally not recommended (see section 4.5).
Neutropenia/agranulocytosis/thrombocytopenia/anaemia. Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving ACE inhibitors. Neutropenia is rare in patients with normal renal function in the absence of other risk factors. Perindopril should be used with caution in patients with collagen vascular diseases, immunosuppressants, allopurinol or procainamide or a combination of these risk factors, especially in the presence of impaired renal function. Some of these patients have developed serious infections, sometimes resistant to intensive antibiotic therapy. Periodic monitoring of white blood cell counts is recommended when perindopril is used in such patients. In addition, patients should be advised to report any signs of infection (e.g. sore throat, fever) to their physician (see sections 4.5 and 4.8).
Hypersensitivity/angioedema (angioedema). Rare cases of angioedema of the face, extremities, lips, tongue, glottis and/or larynx have been reported in patients treated with ACE inhibitors, including perindopril (see section 4.8). This may occur at any time during treatment. In such cases, the drug should be discontinued immediately and the patient should be monitored until symptoms resolve. If the swelling is limited to the face and lips, the patient usually improves without treatment, although antihistamines have been useful in reducing symptoms. Angioedema associated with laryngeal oedema can be fatal. If swelling involves the tongue, glottis, or larynx, which may lead to airway obstruction, urgent emergency treatment is required, which may include subcutaneous administration of epinephrine 1:1000 (0.3–0.5 ml) and/or airway management. Angioedema has been reported more frequently in black patients receiving ACE inhibitors than in non-black patients. Patients with a history of angioedema unrelated to ACE inhibitors are at increased risk of developing angioedema while receiving ACE inhibitors. Rare cases of intestinal angioedema have been reported in patients receiving ACE inhibitors. These patients have presented with abdominal pain (with or without nausea and vomiting); sometimes intestinal angioedema was not accompanied by previous facial angioedema and C1-esterase inhibitor levels were normal. The diagnosis of angioedema was made by procedures such as abdominal computed tomography or ultrasound, or during surgery; after discontinuation of the ACE inhibitor, the symptoms of angioedema disappeared. In patients who present with abdominal pain while taking ACE inhibitors, a differential diagnosis should be made to exclude intestinal angioedema. Concomitant use of perindopril with sacubitril/valsartan is contraindicated due to an increased risk of angioedema (see section 4.3). Sacubitril/valsartan should not be initiated earlier than 36 hours after the last dose of perindopril. If treatment with sacubitril/valsartan is discontinued, perindopril therapy should be initiated no earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.5). Concomitant use of other neutral endopeptidase (NEP) inhibitors (e.g. racecadotril) and ACE inhibitors may also lead to an increased risk of angioedema (see section 4.5). Therefore, a careful benefit-risk assessment should be performed before initiating treatment with NEP inhibitors (e.g. racecadotril) in patients taking perindopril.
Concomitant use of mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus). Patients receiving concomitant mTOR inhibitors may be at increased risk of developing angioedema, including swelling of the airways or tongue, with or without respiratory compromise (see section 4.5).
Anaphylactoid reactions during desensitization. Isolated cases of prolonged, life-threatening anaphylactoid reactions have been reported in patients receiving ACE inhibitors during desensitization therapy with bee venom. ACE inhibitors should be used with caution in allergic patients after desensitization and should be avoided during immunotherapy with bee venom. However, in patients requiring both ACE inhibitors and desensitization, such reactions can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before desensitization therapy.
Anaphylactoid reactions during LDL plasmapheresis: Life-threatening anaphylactoid reactions have been reported rarely in patients receiving ACE inhibitors during LDL plasmapheresis using dextran sulfate. These reactions can be avoided by temporarily withholding ACE inhibitor therapy prior to each plasmapheresis.
Patients on hemodialysis: Anaphylactoid reactions have been reported in patients receiving ACE inhibitors while on hemodialysis using high-flux polyacrylic membranes (e.g., AN 69®). Such patients should be treated with a different type of dialysis membrane or a different class of antihypertensive agent.
Patients after kidney transplantation: There is no experience in prescribing perindopril tert-butylamine to patients after a recent kidney transplantation.
Hypotension. Symptomatic hypotension has been reported in patients with symptomatic heart failure with or without concomitant renal insufficiency. Symptomatic hypotension is more likely to occur in patients with more severe heart failure, those receiving high doses of loop diuretics, those with hyponatraemia or those with functional renal insufficiency. To reduce the risk of symptomatic hypotension, patients should be closely monitored during initiation of therapy and during dose titration. The same precautions apply to patients with ischaemic heart disease or cerebrovascular disease, in whom an excessive fall in blood pressure could result in myocardial infarction or stroke.
Coronary heart disease: If an episode of unstable angina (of any severity) occurs during the first month of treatment with perindopril, the risk/benefit ratio should be carefully weighed before deciding whether to continue therapy.
Special precautions related to indapamide
Hepatic encephalopathy: In patients with impaired liver function, the use of thiazide and thiazide-like diuretics may cause hepatic encephalopathy. Hepatic encephalopathy is a contraindication to the use of the drug.
Photosensitivity: Photosensitivity reactions have been reported with thiazide and thiazide-like diuretics (see section 4.8). If photosensitivity reactions occur during treatment, discontinuation of the drug is recommended. If re-administration is necessary, it is recommended to protect exposed areas from the sun or artificial ultraviolet light sources.
Precautions.
Precautions common to perindopril and indapamide
Renal impairment. In case of severe renal insufficiency (creatinine clearance < 30 ml/min), replace
