Instructions for Perindopress tablets 8 mg No. 30
Composition
active ingredient: perindopril;
1 tablet contains 4 mg or 8 mg of perindopril tert-butylamine, corresponding to 3.338 mg or 6.676 mg of perindopril;
Excipients: lactose monohydrate, microcrystalline cellulose, 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 and a score.
Pharmacotherapeutic group
Angiotensin-converting enzyme (ACE) inhibitors, monocomponent. Perindopril. ATC code C09A A04.
Pharmacological properties
Pharmacodynamics.
Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (angiotensin-converting enzyme - ACE). The converting enzyme, or kinase, is an exopeptidase that enables the conversion of angiotensin I to the vasoconstrictor angiotensin II and also causes the breakdown of the vasodilator bradykinin to an inactive heptapeptide. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which increases the activity of renin in the blood plasma (via a feedback mechanism) and reduces the secretion of aldosterone. Since ACE inactivates bradykinin, inhibition of ACE also leads to an increase in the activity of the circulating and local kallikrein-kinin system (which also leads to the activation of the prostaglandin system). This mechanism of action causes the reduction in blood pressure by ACE inhibitors and is partly responsible for the appearance of some side effects (e.g. cough).
Perindopril tert-butylamine acts through its active metabolite, perindoprilat. Other metabolites have no activity in inhibiting ACE under experimental conditions.
Arterial hypertension.
Perindopril effectively lowers blood pressure in all degrees of arterial hypertension: mild, moderate and severe; a decrease in systolic and diastolic blood pressure is observed in the patient both in the supine and standing positions.
Perindopril reduces peripheral vascular resistance, which leads to a decrease in blood pressure. As a result, peripheral blood flow increases without affecting heart rate.
Typically, renal blood flow also increases, while glomerular filtration rate is largely unchanged.
The maximum antihypertensive effect develops 4–6 hours after a single dose and persists for at least 24 hours: the T/P ratio (minimum efficacy/maximum efficacy during the day) of perindopril is 87–100%.
Blood pressure decreases rapidly. In patients who respond to treatment, blood pressure normalization occurs within a month and is maintained without tachyphylaxis.
There is no withdrawal effect when perindopril is discontinued.
Perindopril reduces left ventricular hypertrophy.
Clinical studies have shown that perindopril has vasodilating properties. It improves the elasticity of large arteries and reduces the ratio of wall thickness to lumen for small arteries.
Combination therapy with a thiazide diuretic has an additive synergistic effect. The combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of diuretic-induced hypokalemia.
Heart failure.
In experimental studies, congestive heart failure was induced by coronary artery ligation, after which it was proven that Perindopril® reduces myocardial hypertrophy and excessive subendocardial collagen, restores the myosin to isoenzyme ratio, and reduces the incidence of reperfusion arrhythmia.
Perindopril tert-butylamine facilitates the work of the heart by reducing pre- and afterload on the heart.
Studies involving patients with heart failure have demonstrated:
reduction in filling pressure of the right and left ventricles;
reduction of systemic peripheral resistance;
increase in cardiac index and improvement in cardiac output;
increased regional blood flow in the myocardial muscles.
In comparative studies, the initial administration of 2 mg perindopril to patients with mild to moderate heart failure was not associated with any significant reduction in blood pressure compared with placebo.
Pharmacokinetics.
Absorption.
After oral administration, perindopril is rapidly absorbed, with peak plasma concentrations occurring within 1 hour. The plasma half-life of perindopril is 1 hour.
Perindopril is a prodrug. 27% of the total amount of perindopril taken is determined in the blood in the form of an active metabolite - perindoprilat. In addition to the active metabolite - perindoprilat, the drug forms 5 metabolites that are inactive. The maximum concentration of perindoprilat in the blood plasma is reached 3-4 hours after administration.
Food intake reduces the conversion of perindopril to perindoprilat, thus reducing its bioavailability, therefore the daily dose of perindopril tert-butylamine is recommended to be taken once in the morning before meals.
There is a linear relationship between the dose of perindopril and its concentration in blood plasma.
The volume of distribution of unbound perindoprilat is approximately 0.2 l/kg. The binding of perindoprilat to plasma proteins is 20%, mainly to angiotensin-converting enzyme, but this indicator is dose-dependent.
Breeding.
Perindoprilat is excreted in the urine. The terminal half-life of the unbound fraction is approximately 17 hours. Steady-state plasma concentrations are reached within 4 days of initiation of treatment.
Special patient groups.
The elimination of perindoprilat is slowed in elderly patients and in patients with heart or renal failure. It is recommended to select the dose for such patients taking into account the degree of insufficiency (creatinine clearance).
Dialysis clearance of perindoprilat is 70 ml/min.
The kinetics of perindopril are altered in patients with cirrhosis: the hepatic clearance of perindopril is halved. However, the amount of perindoprilat formed is not reduced. Therefore, no dose adjustment is required in such patients.
Indication
Arterial hypertension.
Heart failure.
Prevention of recurrent stroke in patients with cerebrovascular disease.
Prevention of cardiovascular complications in patients with documented stable coronary heart disease.
Long-term treatment reduces the risk of myocardial infarction and heart failure (according to the results of the EUROPA study).
Contraindication
Hypersensitivity to the active substance or to any of the excipients, or to any other ACE inhibitor.
History of angioedema after use of an ACE inhibitor.
Idiopathic or hereditary angioedema.
Concomitant administration with medicinal products containing the active substance aliskiren in patients with renal insufficiency (glomerular filtration rate < 60 ml/min/1.73 m2) or diabetes mellitus (see sections “Special warnings and precautions for use” and “Interaction with other medicinal products and other types of interactions”).
Concomitant use with sacubitril/valsartan: Perindopril/Indapamide should not be started earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.4 and 4.5).
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").
Pregnancy or planning to become pregnant (see section "Use during pregnancy or breastfeeding").
Interaction with other medicinal products and other types of interactions
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 a higher incidence of adverse reactions such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see sections 4.3 and 4.4).
Medicines that increase the risk of developing angioedema.
Concomitant use of perindopril with sacubitril/valsartan is contraindicated as it increases the risk of angioedema. Sacubitril/valsartan should not be started earlier than 36 hours after the last dose of perindopril. Perindopril therapy should not be started earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.4).
Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and gliptins (e.g. linagliptin, saxagliptin, sitagliptin, vildagliptin) increases the risk of angioedema (see section 4.4).
Drugs that cause hyperkalemia.
Serum potassium levels are usually within normal limits, but hyperkalemia may occur in some patients taking Perindopril/Indapamide. Some medicinal products or therapeutic classes of medicinal products may cause hyperkalemia, including aliskiren, potassium salts, potassium-sparing diuretics (e.g. spironolactone, triamterene or amiloride), ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs (NSAIDs), heparins, immunosuppressants such as ciclosporin or tacrolimus, trimethoprim and co-trimoxazole (trimethoprim/sulfamethoxazole), since trimethoprim acts as a potassium-sparing diuretic, similar to amiloride. Concomitant use of these medicinal products increases the risk of hyperkalemia. Therefore, concomitant use of Perindopril/Indapamide with these medicinal products is not recommended. If concomitant use of these substances is necessary, they should be used with caution and serum potassium levels should be closely monitored.
Aliskiren. The concomitant use of aliskiren and perindopril is contraindicated in patients with diabetes mellitus and patients with impaired renal function - due to the increased risk of hyperkalemia, worsening of renal function, cardiovascular morbidity and mortality - and is not recommended for all other patient groups (see section "Special warnings and precautions for use").
Extracorporeal treatments that result in contact of blood with negatively charged surfaces, such as high-flux dialysis or hemofiltration membranes (e.g. polyacrylic membranes) and low-density lipoprotein apheresis with dextran sulfate, increase the risk of severe anaphylactoid reactions (see section 4.3). If such treatment is necessary, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive drug.
Sacubitril/valsartan. Concomitant use of perindopril with sacubitril/valsartan is contraindicated because concomitant neprilysin and ACE inhibition increases 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).
Concurrent use is not recommended.
Aliskiren. The concomitant use of aliskiren and perindopril is not recommended in any patient due to an increased risk of hyperkalemia, worsening renal function, cardiovascular morbidity and mortality, and is generally contraindicated in diabetic patients and patients with impaired renal function.
Concomitant use of ACE inhibitors and angiotensin receptor blockers. Published data suggest that in patients with established atherosclerosis, heart failure, or diabetes with target organ damage, concomitant use of ACE inhibitors and angiotensin receptor blockers is associated with an increased incidence of hypotension, syncope, hyperkalemia, and deterioration of renal function (including acute renal failure) compared with monotherapy with drugs that affect the renin-angiotensin-aldosterone system. Dual blockade (i.e., the combination of an ACE inhibitor and angiotensin II receptor antagonists) may be used in selected cases with careful monitoring of renal function, potassium levels, and blood pressure.
Estramustine: Increased risk of adverse reactions such as angioedema.
Co-trimoxazole (trimethoprim/sulfamethoxazole): Patients receiving co-trimoxazole (trimethoprim/sulfamethoxazole) are at increased risk of developing hyperkalemia (see section 4.4).
Potassium-sparing diuretics (e.g. triamterene, amiloride), potassium salts. Hyperkalemia (including fatal) may occur, especially in patients with renal insufficiency (additive hyperkalemic effect). These drugs are not recommended for concomitant use with perindopril (see section "Special warnings and precautions for use"). However, if concomitant use of these substances is necessary, they should be used with caution and with frequent monitoring of plasma potassium.
Lithium. When using ACE inhibitors with lithium preparations, a reversible increase in the concentration of lithium in the blood plasma is possible and, accordingly, an increase in the risk of its toxic effects. It is not recommended to use perindopril with lithium preparations. In case of proven need for such an appointment, it is necessary to carefully monitor the level of lithium in the blood plasma (see section "Special instructions").
Concomitant use requiring special attention.
Antidiabetic agents (insulin, oral hypoglycemic agents). According to epidemiological studies, the simultaneous use of ACE inhibitors and hypoglycemic agents (insulin, oral hypoglycemic agents) may lead to an increase in the hypoglycemic effect with the risk of hypoglycemia. This phenomenon may occur most often in the first weeks of combined treatment and in patients with renal insufficiency.
Baclofen: Concomitant use of baclofen may increase the antihypertensive effect. Blood pressure monitoring and appropriate dose adjustment of antihypertensive agents may be necessary.
Diuretics. In patients taking diuretics, especially those with impaired water and electrolyte metabolism, an excessive decrease in blood pressure may occur after starting treatment with an ACE inhibitor. The likelihood of developing a hypotensive effect is reduced by discontinuing the diuretic, increasing circulating blood volume, or salt intake before starting therapy with perindopril tert-butylamine. Treatment should be initiated at low doses and titrated gradually.
In congestive heart failure on diuretic therapy: ACE inhibitor therapy should be initiated at the lowest dose, possibly after reducing the diuretic dose.
In any case, it is necessary to monitor kidney function (creatinine level) during the first weeks of treatment with an ACE inhibitor.
Potassium-sparing diuretics (eplerenone, spironolactone). In the case of simultaneous use of eplerenone or spironolactone in doses from 12.5 mg to 50 mg per day with low doses of an ACE inhibitor, it should be borne in mind that:
If the recommendations for the administration of this combination are not followed, there is a risk of hyperkalemia (possibly fatal) during the treatment of patients with NYHA [New York Heart Association] class II–IV heart failure and an ejection fraction < 40%, who were previously treated with an ACE inhibitor and a loop diuretic;
before prescribing such a combination, one should make sure that there is no hyperkalemia and renal failure;
It is recommended to carefully monitor potassium and creatinine levels weekly during the first month of treatment and monthly thereafter.
NSAIDs, including acetylsalicylic acid ≥ 3 g/day. A weakening of the antihypertensive effect is possible during the simultaneous use of ACE inhibitors with NSAIDs, such as: acetylsalicylic acid in anti-inflammatory doses, COX-2 inhibitors, non-selective NSAIDs. The simultaneous use of ACE inhibitors and NSAIDs increases the risk of worsening of renal function, including the development of acute renal failure, an increase in plasma potassium levels, especially in patients with a history of impaired renal function. Such a combination should be prescribed with caution, especially in elderly patients. Patients should be rehydrated, and attention should be paid to monitoring renal function immediately after the appointment of combination therapy and periodically thereafter.
Racecadotril: ACE inhibitors (e.g. perindopril) are known to cause angioedema. This risk is 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 are at increased risk of developing angioedema (see section 4.4).
Simultaneous use, which requires some attention.
Antihypertensives and vasodilators. Concomitant use of antihypertensives may increase the hypotensive effect of perindopril tert-butylamine. Concomitant use with nitroglycerin and other nitrates, or with other vasodilators may contribute to an additional decrease in blood pressure.
Gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin): Patients receiving a combination of a gliptin and an ACE inhibitor are at increased risk of angioedema due to the gliptin's inhibition of dipeptidyl peptidase-IV (DPP-IV).
Concomitant use of certain anesthetics, tricyclic antidepressants, or antipsychotics with ACE inhibitors may lead to a further decrease in blood pressure (see section "Special warnings and precautions for use").
Sympathomimetics may weaken the antihypertensive effect of ACE inhibitors.
Gold: A nitrate-like reaction (symptoms include facial flushing, nausea, vomiting, and hypotension) has been reported rarely in patients receiving concomitant ACE inhibitors, including perindopril, and injectable gold (sodium aurothiomalate).
Application features
Stable ischemic 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.
Arterial hypotension.
If hypotension occurs, the patient should be placed in the supine position and, if necessary, intravenously administered 0.9% (9 mg/ml) sodium chloride solution. Transient hypotension is not a contraindication to continued use of the drug, which can usually be used without any problems after volume repletion and blood pressure elevation.
In some patients with congestive heart failure with normal or low blood pressure, perindopril tert-butylamine may cause an additional decrease in systemic blood pressure. This effect is expected and usually does not require discontinuation of the drug. If hypotension becomes symptomatic, a dose reduction or discontinuation of the drug may be necessary.
Aortic and mitral valve stenosis / hypertrophic cardiomyopathy.
As with other ACE inhibitors, perindopril tert-butylamine should be administered with caution to patients with mitral valve stenosis or left ventricular outflow obstruction (aortic stenosis or hypertrophic cardiomyopathy).
Kidney failure.
In case of renal insufficiency (creatinine clearance < 60 ml/min), the initial dose of perindopril should be adjusted according to the patient's creatinine clearance (see section 4.2) and then adjusted according to the patient's response to treatment. In such patients, continuous monitoring of potassium and creatinine levels is usually recommended (see section 4.8).
In patients with symptomatic heart failure, hypotension occurring at the start of ACE inhibitors may lead to deterioration of renal function, in some cases with the development of acute renal failure, which is usually reversible.
In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, increases in blood urea and serum creatinine have been observed when using ACE inhibitors, which usually return to normal after discontinuation of treatment. This is especially true in patients with renal insufficiency. In the presence of concomitant renovascular hypertension, the risk of severe arterial hypotension and renal insufficiency increases. Treatment of such patients should be initiated under close medical supervision, with low doses and with careful titration.
Given these recommendations, treatment with diuretics may contribute to the occurrence of arterial hypotension, so they should be discontinued and renal function should be monitored during the first weeks of treatment with perindopril tert-butylamine.
Some hypertensive patients without pre-existing renovascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, particularly when perindopril tert-butylamine has been given concomitantly with a diuretic. However, this is more likely to occur in patients with pre-existing renal impairment. A dose reduction and/or discontinuation of the diuretic and/or perindopril tert-butylamine may be necessary.
Patients on hemodialysis.
Anaphylactic-type reactions have been reported in patients receiving hemodialysis with high-flux polyacrylic membranes and concomitant ACE inhibitors. Therefore, a decision should be made to use a different type of dialysis membrane or a different class of antihypertensive drug in these patients.
Patients after kidney transplantation.
There is no experience with the administration of perindopril tert-butylamine to patients after a recent kidney transplant.
Renovascular hypertension.
When ACE inhibitors are administered to patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney, there is an increased risk of hypotension and renal failure (see section 4.3). Diuretic therapy may be a beneficial factor. Loss of renal function may be manifested by minimal changes in serum creatinine levels even in patients with stenosis of the artery to a single kidney.
Hypersensitivity/angioedema.
Rare cases of angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx have been reported in patients receiving ACE inhibitors, including perindopril tert-butylamine (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. In those rare cases where the swelling is limited to the face and lips, the patient usually improves without treatment. Antihistamines may be useful in reducing symptoms.
Patients with a history of angioedema unrelated to ACE inhibitor therapy are at increased risk of developing angioedema while receiving an ACE inhibitor (see section 4.3).
Rare cases of intestinal angioedema have been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases, there was no previous history of facial angioedema and C-1-esterase levels were normal. The diagnosis of intestinal angioedema was made by abdominal computed tomography or ultrasound, or at the time of surgery. Symptoms of angioedema resolved after discontinuation of the ACE inhibitor. Intestinal angioedema should be considered in the differential diagnosis of patients with abdominal pain receiving ACE inhibitors.
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 started until 36 hours after the last dose of perindopril. If treatment with sacubitril/valsartan is discontinued, perindopril should not be started until 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.5).
The concomitant use of neutral endopeptidase (NEP) inhibitors, such as racecadotril, and ACE inhibitors also increases the 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.
Patients treated concomitantly with mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and gliptins (e.g. linagliptin, saxagliptin, sitagliptin, vildagliptin) are at increased risk of developing angioedema, e.g. swelling of the airways or tongue, with or without respiratory impairment (see section 4.5).
Caution should be exercised when initiating treatment with racecadotril, mTOR inhibitors (e.g., sirolimus, everolimus, temsirolimus), and gliptins (e.g., linagliptin, saxagliptin, sitagliptin, vildagliptin) in patients already taking ACE inhibitors.
Anaphylactoid reactions during low-density lipoprotein (LDL) plasmapheresis.
Rarely, life-threatening anaphylactoid reactions have occurred in patients receiving ACE inhibitors during LDL plasmapheresis using dextran sulfate. Anaphylactoid reactions can be avoided by temporarily stopping ACE inhibitor therapy before each plasmapheresis.
Anaphylactoid reactions during desensitization therapy.
Life-threatening anaphylactoid reactions may occur in patients taking ACE inhibitors during desensitization treatment with medicinal products containing bee venom. These reactions can be avoided by temporarily stopping the ACE inhibitor, but the reactions may recur if provocation tests are not carried out carefully.
Liver failure.
Cases of a syndrome that begins with cholestatic jaundice and progresses to transient hepatic necrosis, sometimes fatal, have been reported rarely in patients receiving an ACE inhibitor. The mechanism of this syndrome is unknown. Patients who develop jaundice or significant elevations of liver enzymes while receiving an ACE inhibitor should discontinue the drug and receive appropriate medical evaluation and treatment (see section 4.8).
Neutropenia/agranulocytosis/thrombocytopenia/anemia.
Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported in patients taking ACE inhibitors. Neutropenia is rare in patients with normal renal function and in the absence of other risk factors. Perindopril should be administered with great caution to patients with collagen vascular diseases, immunosuppressants, allopurinol or procainamide or a combination of these aggravating factors, especially in the presence of pre-existing renal impairment. Serious infections may occasionally develop in these patients, which in rare cases may not respond to intensive antibiotic therapy. If perindopril is prescribed to such patients, periodic monitoring of the white blood cell count is recommended. Patients should be advised to report any signs of infection (sore throat, fever).
Racial factor.
ACE inhibitors cause angioedema more often in black patients than in non-blacks. As with other ACE inhibitors, perindopril is less effective in lowering blood pressure in black patients than in non-blacks, possibly because of lower blood renin levels in these patients.
There have been reports of cough occurring during therapy with ACE inhibitors.
The cough is typically nonproductive, persistent, and resolves after discontinuation of the drug. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.
Surgery/anesthesia.
The drug may block the secondary formation of angiotensin II in response to compensatory renin release in patients undergoing surgery or during anesthesia with drugs that cause hypotension. The drug should be discontinued one day before surgery. In the event of arterial hypotension, if it is believed that it is caused by the specified mechanism, the patient's condition can be normalized by increasing the volume of circulating blood.
Hyperkalemia.
Some patients have experienced increases in serum potassium while taking ACE inhibitors, including perindopril. ACE inhibitors may cause hyperkalemia by inhibiting aldosterone release. This effect is usually minor in patients with normal renal function. Risk factors for hyperkalaemia include renal insufficiency, worsening of renal function, age (over 70 years), diabetes mellitus, intercurrent conditions such as dehydration, acute cardiac decompensation, metabolic acidosis and concomitant use of potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene or amiloride), potassium supplements, potassium-containing salt substitutes or other medicinal products that increase serum potassium (e.g. heparin, co-trimoxazole, also known as trimethoprim/sulfamethoxazole), especially aldosterone antagonists or angiotensin receptor blockers. The use of potassium-containing supplements, potassium-sparing diuretics or potassium-containing salt substitutes, especially in patients with impaired renal function, may lead to significant increases in serum potassium. Hyperkalemia may cause serious, sometimes fatal arrhythmias. Potassium-sparing diuretics and angiotensin receptor blockers should be used with caution in patients receiving ACE inhibitors, and serum potassium and renal function should be closely monitored. If concomitant use of perindopril and any of these agents is considered appropriate, they should be used with caution and with frequent monitoring of serum potassium (see Interactions).
Patients with diabetes.
Diabetic patients taking oral hypoglycemic agents or insulin should have their blood glucose levels closely monitored during the first month of treatment with ACE inhibitors (see section 4.5).
Lithium.
The concomitant use of lithium and perindopril is generally not recommended (see section "Interaction with other medicinal products and other types of interactions").
Potassium-sparing medications, potassium-containing dietary supplements, or potassium-containing salt substitutes.
Concomitant use of perindopril with potassium-sparing medicinal products or potassium-containing food supplements is not recommended.
