Instructions Noliprel Bi-Forte film-coated tablets container No. 30
Composition
active ingredients: perindopril/indapamide;
1 tablet contains 6.79 mg of perindopril, corresponding to 10 mg of perindopril arginine, and 2.5 mg of indapamide;
Excipients: lactose monohydrate, magnesium stearate, maltodextrin, colloidal anhydrous silica, sodium starch glycolate (type A), glycerol, hypromellose, macrogol 6000, titanium dioxide (E 171).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablet, white in color, round in shape.
Pharmacotherapeutic group
Combinations of angiotensin-converting enzyme (ACE) inhibitors. Perindopril and diuretics. ATX code C09B A04.
Pharmacological properties
Pharmacodynamics
Noliprel® Bi-forte is a combination of the ACE inhibitor perindopril arginine 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
Mechanism of action of perindopril
Perindopril is an ACE inhibitor that converts angiotensin I to angiotensin II (a vasoconstrictor substance), additionally stimulating the secretion of aldosterone by the adrenal cortex and the breakdown of bradykinin (a vasodilating substance) to inactive heptapeptides. ACE inhibition leads to: a decrease in aldosterone secretion; an increase in plasma renin activity, while aldosterone has no negative effect; a decrease in total peripheral vascular resistance due to the predominant effect on muscle and renal vessels; 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 reduces cardiac work through a vasodilatory effect on the veins (possibly due to changes in prostaglandin metabolism) – reducing preload – and through a decrease in 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 left and right ventricular filling pressure, a decrease in total peripheral vascular resistance, an increase in cardiac output and an improvement in cardiac index, an increase in regional blood flow in the muscles. The indicators of physical exercise tests are improved.
Mechanism of action of indapamide
Indapamide is a sulfonamide derivative with an indole ring, pharmacologically related to thiazide diuretics. Indapamide inhibits sodium reabsorption in the cortical segment of the kidneys. This increases the excretion of sodium and chlorides and, to a lesser extent, potassium and magnesium in the urine, thereby increasing urine output and providing an antihypertensive effect.
Pharmacodynamic effects
Noliprel® Bi-forte has a dose-dependent antihypertensive effect on systolic (SAT) and diastolic (DBP) blood pressure in patients of any age with arterial hypertension both in the supine and standing positions.
PICXEL is a multicenter, randomized, double-blind, controlled study that evaluated the effect of the combination of perindopril and indapamide on left ventricular hypertrophy compared with enalapril monotherapy as measured by echocardiography. In PICXEL, patients with hypertension and left ventricular hypertrophy (left ventricular mass index > 120 g/m2 in men and > 100 g/m2 in women) were randomized into two groups: one group of patients received 2 mg perindopril tert-butylamine (equivalent to 2.5 mg perindopril arginine)/0.625 mg indapamide, and the other group received 10 mg enalapril once daily for one year. The doses were adjusted according to blood pressure: the dose of perindopril tert-butylamine was increased to 8 mg (equivalent to 10 mg perindopril arginine), indapamide to 2.5 mg, and enalapril to 40 mg once daily. The initial dose was continued by 34% of patients in the perindopril/indapamide group (2 mg perindopril and 0.625 mg indapamide) and 20% in the enalapril group (10 mg). Among all randomized patients, the left ventricular mass index at the end of treatment decreased significantly more in patients receiving perindopril/indapamide (-10.1 g/m²) than in the enalapril group (-1.1 g/m²). The difference between the two groups was -8.3 (95% confidence interval [CI] -11.5 to -5.0, p < 0.0001). The best effect on reducing left ventricular mass index was achieved with the 8 mg perindopril (equivalent to 10 mg perindopril arginine)/2.5 mg indapamide dose. Blood pressure was reduced more effectively in the perindopril/indapamide group: the difference in mean BP reduction between the two groups of patients was -5.8 mmHg (95% CI -7.9 to -3.7, p < 0.0001) for systolic blood pressure and -2.3 mmHg (95% CI -3.6 to -0.9, p = 0.0004) for diastolic blood pressure.
Perindopril effectively lowers blood pressure in all degrees of arterial hypertension: mild, moderate and severe. Reduction of systolic and diastolic blood pressure is observed both in the supine and standing positions. The maximum antihypertensive effect develops 4–6 hours after taking a single dose and persists for more than a day. Perindopril has a high level of final blockade of the ACE inhibitor (approximately 80%) 24 hours after taking it. In patients who have responded to treatment, normalization of blood pressure is achieved after a month and is maintained without the occurrence of tachyphylaxis. Discontinuation of therapy is not accompanied by a withdrawal syndrome. Perindopril has vasodilator properties, restores the elasticity of large arteries, corrects histomorphometric changes in arterial resistance and reduces left ventricular hypertrophy. The addition of a thiazide diuretic, if necessary, leads to additional synergy. The combined use of an ACE inhibitor and a thiazide diuretic reduces the risk of hypokalemia that can occur when the diuretic is prescribed as monotherapy.
Pharmacodynamic effects associated with indapamide
When used as monotherapy, indapamide has an antihypertensive effect that lasts 24 hours. This effect is manifested in 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. Moreover, as shown in studies of different durations (short, medium and long) in patients with hypertension, indapamide does not affect lipid metabolism (triglycerides, low and high density lipoproteins) and does not affect carbohydrate metabolism, even in patients with 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 arginine 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 concentration-dependent.
Biotransformation. Perindopril is a prodrug. Thus, 27% of the administered dose of perindopril enters the bloodstream as 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. However, the amount of perindoprilat formed is not reduced and, therefore, no dose adjustment is required in such patients (see sections “Method of administration and dosage” and “Special warnings and precautions for use”).
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
Treatment of arterial hypertension in patients requiring the use of perindopril arginine at a dose of 10 mg and indapamide at a dose of 2.5 mg.
Contraindication
Related to perindopril:
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 pregnancy (see section "Use during pregnancy or breastfeeding");
simultaneous use with drugs containing aliskiren in patients with diabetes mellitus or impaired renal function (glomerular filtration rate < 60 ml/min/1.73 m2) (see section "Interaction with other medicinal products and other types of interactions");
simultaneous use with sacubitril/valsartan (see sections “Special instructions for use” and “Interaction with other medicinal products and other types of interactions”);
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 the active substance or to any other sulfonamides; severe and moderate renal impairment (creatinine clearance < 60 ml/min); hepatic encephalopathy; severe hepatic impairment; hypokalemia; as a general rule, this medicinal product should not be administered in combination with non-antiarrhythmic drugs that may cause the development of torsades de pointes; breastfeeding (see section "Use during pregnancy or breastfeeding").
Related to the drug Noliprel® Bi-forte:
hypersensitivity to any excipient.
Due to the lack of sufficient clinical experience, Noliprel® Bi-forte 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. 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.
Non-steroidal anti-inflammatory drugs (NSAIDs) (including aspirin ≥ 3 g/day). When ACE inhibitors are used concomitantly with non-steroidal anti-inflammatory drugs, such as acetylsalicylic acid at anti-inflammatory doses, COX-2 inhibitors and non-selective NSAIDs, attenuation of the antihypertensive effect may occur. Concomitant use of ACE inhibitors and NSAIDs may increase the risk of worsening of renal function, including acute renal failure, and an increase in serum potassium, especially in patients with impaired renal function. This combination should be administered with caution, especially in the elderly. Patients should be rehydrated before starting treatment and renal function should be monitored at the start 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 worsening renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see sections 4.3 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).
Extracorporeal therapies: Extracorporeal therapies that bring blood into contact with negatively charged surfaces, such as dialysis or hemofiltration using certain membranes with high hydraulic permeability (e.g. polyacrylonitrile) and low-density lipoprotein 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).
Concomitant use is not recommended.
Aliskiren: In all other patient groups, as well as in patients with diabetes mellitus or renal impairment, the risk of hyperkalemia, worsening of renal function 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 worsening renal function (including acute renal failure) compared with the use of a single agent that acts on the renin-angiotensin-aldosterone system. 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 and 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 have shown that 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.
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 II–IV functional classes according to the New York Heart Association (NYHA) scale 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 levels 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 by concomitant use 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
Antihypertensives and vasodilators. Concomitant use of these drugs may enhance the hypotensive effects of perindopril. Concomitant use with nitroglycerin and other nitrates or with other vasodilators may contribute to an additional decrease in blood pressure.
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: Rare cases of nitritoid reactions (facial flushing, nausea, vomiting and hypotension) have been reported in patients treated with injectable gold preparations (sodium aurothiomalate) and concomitant use of an ACE inhibitor, including perindopril.
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. A decrease in plasma potassium levels should be prevented and, if necessary, corrected, and the QT interval should be monitored.
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. Decreased blood potassium levels increase the toxic effects of digitalis preparations. Blood potassium levels and ECG should be monitored and therapy reviewed if necessary.
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 may be 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.
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 concentrations, 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).
Special precautions related to perindopril
Dual blockade of the renin-angiotensin-aldosterone system (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 RAAS blockade is considered absolutely necessary, it should only be carried out 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 may be fatal. If swelling spreads to 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 measures to maintain a patent airway. 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 treated with 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; symptoms of angioedema resolved after discontinuation of the ACE inhibitor. In patients presenting with abdominal pain while taking ACE inhibitors, a differential diagnosis should be made to exclude intestinal angioedema. The concomitant use of perindopril with sacubitril/valsartan is contraindicated due to an increased risk of angioedema (see section 4.3).
Sacubitril/valsartan should be initiated no 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 made 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 distress) (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 stopping the ACE inhibitor at least 24 hours before starting desensitization therapy.
Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis. Life-threatening anaphylactoid reactions have been reported rarely in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. These reactions can be avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis.
Primary aldosteronism: Patients with primary hyperaldosteronism usually do not respond to antihypertensive medicinal products that act by inhibiting the renin-angiotensin system. Therefore, the use of this medicinal product is not recommended in such patients.
Patients after kidney transplantation: There is no experience with the use of perindopril arginine in patients after a recent kidney transplantation.
Hypotension: Symptomatic hypotension has been reported in patients with symptomatic heart failure and concomitant renal insufficiency.
