Corderia AM tablets 8 mg + 5 mg blister No. 30

Instructions Corderia AM tablets 8 mg + 5 mg blister No. 30

Composition

active ingredients: perindopril, amlodipine;

1 tablet contains:

perindopril tert-butylamine 4 mg, equivalent to 3.338 mg perindopril, and amlodipine besylate 6.935 mg, equivalent to 5 mg amlodipine;

or perindopril tert-butylamine 4 mg, equivalent to 3.338 mg perindopril, and amlodipine besylate 13.87 mg, equivalent to 10 mg amlodipine;

or perindopril tert-butylamine 8 mg, equivalent to 6.676 mg perindopril, and amlodipine besylate 6.935 mg, equivalent to 5 mg amlodipine;

or perindopril tert-butylamine 8 mg, equivalent to 6.676 mg perindopril, and amlodipine besylate 13.87 mg, equivalent to 10 mg amlodipine;

Excipients: lactose monohydrate; microcrystalline cellulose; crospovidone; sodium bicarbonate; colloidal anhydrous silicon dioxide; magnesium stearate.

Dosage form

Pills.

Main physicochemical properties: round biconvex tablets from white to almost white in color.

Pharmacotherapeutic group

Drugs that affect the cardiovascular system.

Drugs affecting the renin-angiotensin system. ACE inhibitors, combinations. ACE inhibitors and calcium channel blockers. Perindopril and amlodipine.

ATX code C09B B04.

Pharmacological properties

Pharmacodynamics.

Perindopril

Mechanism of action

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 plasma renin (by inhibiting the negative feedback of renin release) 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 (and thus also leads to the activation of the prostaglandin system). This mechanism of action is responsible for the blood pressure lowering effect of ACE inhibitors and is partly responsible for some of their side effects (e.g., cough).

Perindopril acts through its active metabolite, perindoprilat. Other metabolites do not demonstrate activity in inhibiting ACE under experimental conditions.

Clinical efficacy and safety

Arterial hypertension

Perindopril effectively reduces blood pressure in all degrees of arterial hypertension: mild, moderate and severe; a decrease in systolic and diastolic blood pressure is observed both in the patient's supine and standing position.

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 (GFR) is usually unchanged.

The maximum antihypertensive effect develops 4–6 hours after a single dose and persists for at least 24 hours: the T/P ratio (effectiveness before the next dose/maximum effectiveness) 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 the occurrence of 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 in small arteries.

Prevention of cardiovascular complications in patients with documented stable coronary artery disease (CAD)

EUROPA is an international multicenter, randomized, double-blind, placebo-controlled clinical trial that lasted 4 years. 12,218 adult patients were randomized to groups: 6,110 patients received 8 mg perindopril tert-butylamine (equivalent to 10 mg perindopril arginine) and 6,108 patients received placebo. The study included patients with confirmed ischemic heart disease and without clinically confirmed heart failure. Overall, 90% of patients had a history of myocardial infarction and/or revascularization surgery. Most patients in the study received perindopril in addition to standard therapy: antiplatelet agents, lipid-lowering drugs and β-blockers.

The primary efficacy endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction and/or cardiac arrest with subsequent successful resuscitation. Perindopril tert-butylamine 8 mg once daily resulted in a significant absolute reduction in the primary endpoint of 1.9% (relative risk reduction of 20%, 95% CI [9.4; 28.6] — p

Amlodipine

Amlodipine is a calcium ion flux inhibitor belonging to the dihydropyridine group (slow calcium channel blocker or calcium ion antagonist) and blocks the transmembrane flow of calcium ions into myocardial and vascular smooth muscle cells.

The mechanism of antihypertensive action of amlodipine is due to a direct relaxant effect on vascular smooth muscle. The exact mechanism by which amlodipine reduces angina is not fully understood, but amlodipine reduces overall exercise ischemia through the following actions:

- amlodipine dilates peripheral arterioles and thus reduces total peripheral resistance (afterload). Since the heart rate does not change, the reduction in workload on the heart reduces myocardial energy consumption and oxygen demand;

- amlodipine also partially dilates the main coronary arteries and coronary arterioles in both intact and ischemic areas of the myocardium. This dilation increases the supply of oxygen to the myocardium in patients with vasospastic angina (Prinzmetal's angina or variant angina).

Clinical efficacy and safety

In patients with hypertension, once-daily administration of amlodipine provides clinically significant reductions in blood pressure over 24 hours in both the supine and standing positions. Due to its slow onset of action, amlodipine does not cause acute hypotension.

In patients with angina, once-daily administration of amlodipine increases total exercise time, time to angina attack, and time to 1 mm ST-segment depression, reduces the frequency of angina attacks, and reduces the need for nitroglycerin.

Amlodipine is not associated with any negative metabolic effects or changes in plasma lipid levels, so it can be used in patients with asthma, diabetes, and gout.

Coronary heart disease (CHD)

The efficacy of amlodipine in preventing clinical events in patients with coronary heart disease (CHD) was evaluated in an independent, multicenter, randomized, double-blind, placebo-controlled trial involving 1997 patients, CAMELOT (Comparison of Amlodipine to Enalapril in Limiting Thrombosis). Over 2 years, 663 patients received amlodipine 5–10 mg, 673 patients received enalapril 10–20 mg, and 655 patients received placebo in addition to standard therapy with statins, β-blockers, diuretics, and aspirin. The main efficacy results are presented in the table below. The results indicate that treatment with amlodipine was associated with fewer hospitalizations for angina and fewer revascularization procedures in patients with CHD.

Number of cases of significant clinical outcomes in the CAMELOT study

Heart failure

Haemodynamic studies and exercise-controlled clinical trials in patients with heart failure of NYHA functional class II–IV showed that amlodipine did not cause clinical deterioration in terms of exercise tolerance, left ventricular ejection fraction and clinical symptoms.

PRAISE-2 is a long-term, placebo-controlled study. The aim of the study was to evaluate the effect of amlodipine in patients with NYHA functional class III–IV heart failure without clinical symptoms or objective evidence of or underlying ischemic disease. Patients participating in the study were receiving long-term ACE inhibitors, digitalis drugs, and diuretics. The study showed that amlodipine did not affect all-cause cardiovascular mortality. In the study, amlodipine was associated with an increased number of reports of pulmonary edema.

ALLHAT — a study of different types of treatments to prevent heart attacks

The ALLHAT (Antihypertensive and Lipid-lowering Treatment for Heart Attack Prevention) randomized, double-blind, morbidity/mortality trial was conducted in patients with mild to moderate hypertension to compare current therapeutic agents: amlodipine 2.5–10 mg/day (calcium channel blocker) or lisinopril 10–40 mg/day (ACE inhibitor) as first-line therapy and the thiazide diuretic chlorthalidone 12.5–25 mg/day.

The study included 33,357 hypertensive patients aged 55 years and older who were followed for a median of 4.9 years. Patients had at least one additional cardiovascular risk factor, including previous myocardial infarction or stroke >6 months before study entry or evidence of other atherosclerotic cardiovascular disease (overall 51.5%), type 2 diabetes (36.1%), high-density lipoprotein (HDL) dyslipidemia

The primary endpoint was a composite of fatal CHD or nonfatal myocardial infarction. There was no statistically significant difference in the primary endpoint between amlodipine-based and chlorthalidone-based therapy: relative risk 0.98, 95% CI (0.90–1.07) p = 0.65. Regarding secondary endpoints, the incidence of heart failure (a component of the composite cardiovascular endpoint) was significantly higher in the amlodipine group compared with the chlorthalidone group (10.2% vs. 7.7%, relative risk 1.38, 95% CI [1.25–1.52] p

Properties that are the same for perindopril and amlodipine

The ASCOT-BLPA (Anglo-Scandinavian Study of Cardiovascular Outcomes - Antihypertensive Arm) morbidity and mortality study was conducted in 19,257 patients aged 40 to 79 years with hypertension and at least 3 of the following cardiovascular risk factors: left ventricular hypertrophy (detected by ECG or echocardiography), other abnormalities detected on the electrocardiogram, type 2 diabetes mellitus, peripheral arterial disease, previous stroke or transient ischemic attack, male gender, age ≥55 years, microalbuminuria or proteinuria, smoking, plasma total cholesterol to high-density lipoprotein (HDL) cholesterol ratio of 6 or greater, and family history of early-onset CHD.

The primary objective of the study was to evaluate and compare the long-term effects of two antihypertensive therapy regimens on the combined endpoint of non-fatal myocardial infarction (including asymptomatic myocardial infarction) and fatal complications of ischemic heart disease (IHD), namely, amlodipine therapy in combination with perindopril, which was added if necessary to lower blood pressure, compared with atenolol therapy in combination with the diuretic bendroflumethiazide, which was added if necessary to lower blood pressure.

At the end of the study, most patients (78%, 14974 of 19242) were receiving at least two antihypertensive agents and only 15% (1401 of 9634) and 9% (857 of 9608) were receiving monotherapy with amlodipine and atenolol, respectively.

The study was terminated early after a median follow-up of 5.5 years by the Data Safety Monitoring Board (DSMB) because of significantly higher mortality in the atenolol-based group compared to the amlodipine group.

The study showed a non-significant reduction in the primary endpoint of non-fatal myocardial infarction (including asymptomatic myocardial infarction) and fatal coronary heart disease (CHD) by 10% in the amlodipine/perindopril group compared with the atenolol/bendroflumethiazide group. However, there was a significant reduction in all secondary endpoints (except fatal and non-fatal heart failure) in the amlodipine/perindopril group.

Endpoints

The rate and extent of absorption of perindopril and amlodipine both separately and as part of the fixed combination Corderia AM do not differ significantly.

Perindopril

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 reaches the bloodstream in the form of the 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.

Distribution

There is a linear relationship between the dose of perindopril and its concentration in the 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.

The elimination of perindoprilat is slowed in elderly patients and in patients with cardiac or renal insufficiency (see section 4.4). Therefore, routine medical supervision will include frequent monitoring of creatinine and potassium levels.

Liver failure

Dialysis clearance of perindoprilat is 70 ml/min.

The kinetics of perindopril are altered in patients with cirrhosis of the liver: 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 (see section "Special warnings and precautions for use").

Amlodipine

Absorption, distribution, binding to blood plasma proteins

After oral administration of therapeutic doses of amlodipine, it is well absorbed and reaches maximum blood concentrations 6–12 hours after administration. Absolute bioavailability is 64 to 80%. The volume of distribution is approximately 21 l/kg. In vitro studies have shown that approximately 97.5% of circulating amlodipine is bound to plasma proteins.

Food intake does not affect the bioavailability of amlodipine.

Biotransformation/excretion

The plasma half-life is approximately 35–50 hours, which allows the drug to be administered once daily.

Amlodipine is primarily metabolized in the liver to inactive metabolites. 60% of the metabolites are excreted in the urine and 10% in unchanged form.

Elderly patients

The time to reach the maximum concentration of amlodipine in the blood plasma in elderly patients and younger patients is the same. In elderly patients, there is a tendency for amlodipine clearance to decrease and, accordingly, an increase in AUC and half-life. The increase in AUC and half-life in patients with congestive heart failure was consistent with the age characteristics of the studied patients.

Liver failure

There are very limited clinical data on the use of amlodipine in patients with hepatic impairment. In patients with hepatic insufficiency, the clearance of amlodipine is reduced, resulting in a prolonged half-life and an increase in AUC by approximately 40-60%.

Clinical characteristics.

Indication

Arterial hypertension and/or ischemic heart disease (if treatment with perindopril and amlodipine is necessary).

Contraindication

Related to perindopril:

- hypersensitivity to perindopril or to any other ACE inhibitors;

- history of angioedema associated with previous treatment with ACE inhibitors;

- congenital or idiopathic angioedema;

- pregnancy or planning a pregnancy (see section "Use during pregnancy or breastfeeding");

- simultaneous use with medicinal products containing the active substance aliskiren in patients with diabetes mellitus or renal insufficiency (glomerular filtration rate 2) (see section "Interaction with other medicinal products and other types of interactions");

- simultaneous use with sacubitril/valsartan. Corderia AM should not be used earlier than 36 hours after taking the last dose of sacubitril/valsartan (see sections “Special instructions for use” and “Interaction with other medicinal products and other types of interactions”);

- extracorporeal treatment methods that lead to contact of blood 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 amlodipine:

- severe arterial hypotension;

- hypersensitivity to amlodipine or to dihydropyridine derivatives;

- obstruction of the outlet from the left ventricle (for example, severe aortic stenosis);

- heart failure after acute myocardial infarction with unstable hemodynamics.

Related to the drug Corderia AM:

– all of the above contraindications associated with individual components of the fixed combination Corderia AM;

- hypersensitivity to any excipient.

Interaction with other medicinal products and other types of interactions

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 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).

Drugs that increase the risk of angioedema. Concomitant use of ACE inhibitors 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) may lead to an increased risk of angioedema (see section 4.4).

Drugs causing hyperkalemia. Serum potassium levels are usually within normal limits, but hyperkalemia may occur in some patients taking Corderia AM. Some drugs or therapeutic classes of drugs 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 drugs increases the risk of hyperkalemia. Therefore, the concomitant use of Corderia AM with the above-mentioned drugs is not recommended. If concomitant use of these substances is necessary, they should be used with caution and serum potassium should be monitored frequently.

Concomitant use is contraindicated (see Contraindications section).

Aliskiren: In patients with diabetes mellitus or patients with impaired renal function, the risk of hyperkalemia, worsening of renal function, and cardiovascular morbidity and mortality is increased.

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, increase the 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.

Concomitant use is not recommended (see section "Special precautions for use")

Aliskiren: In all other patients, as well as in patients with diabetes mellitus or patients with impaired renal function, the risk of hyperkalemia, worsening of renal function and cardiovascular morbidity and mortality is increased.

Published data indicate that in patients with established atherosclerosis, heart failure, or diabetes mellitus with target organ damage, concomitant use of ACE inhibitors and angiotensin receptor blockers was 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 with angiotensin II receptor antagonists) may be used in individual cases with careful monitoring of renal function, potassium levels, and blood pressure.

Potassium-sparing diuretics (e.g. triamterene, amiloride and others), potassium salts. Occurrence of hyperkalemia (possibly fatal), especially in patients with renal insufficiency (additive hyperkalemic effect). These drugs are not recommended for simultaneous use with perindopril (see section "Special warnings and precautions for use"). However, if the simultaneous use of these substances is necessary, they should be used with caution and frequent monitoring of blood potassium is required. Regarding the use of spironolactone in heart failure, see the section "Medicines with which simultaneous use requires special attention".

Lithium: Concomitant use of lithium and ACE inhibitors is not recommended due to the possibility of reversible increases in serum lithium concentrations and, consequently, increased toxicity (severe neurotoxicity). However, if the need for such a combination is justified, serum lithium concentrations should be monitored (see section 4.4).

Medicinal products, concomitant administration of which requires special attention

Hypoglycemic agents (insulin, oral hypoglycemic agents). Epidemiological studies suggest that the concomitant use of ACE inhibitors and hypoglycemic agents (insulin, oral hypoglycemic agents) may lead to an increased hypoglycemic effect with a risk of hypoglycemia. This phenomenon may occur most often in the first weeks of combined treatment and in the case of renal insufficiency.

Diuretics. In patients taking diuretics, and especially in those with impaired water and electrolyte balance, an excessive decrease in blood pressure may occur after starting treatment with an ACE inhibitor. The likelihood of developing a hypotensive effect is reduced if the diuretic is discontinued, the circulating blood volume is increased, or salt intake is increased before starting perindopril therapy, which should be started at a low dose with a gradual increase. In arterial hypertension, when the previously prescribed diuretic could have caused water/electrolyte depletion, it should be discontinued before starting treatment with an ACE inhibitor (in such cases, the diuretic can be resumed over time) or the ACE inhibitor should be prescribed at a low dose with a gradual increase. In congestive heart failure on a diuretic, the ACE inhibitor should be started at the lowest dose, possibly after a reduction in the dose of the diuretic. 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). Special care should be taken when eplerenone or spironolactone 12.5 mg to 50 mg daily are used with low doses of an ACE inhibitor. If the recommendations for the use of this combination are not followed, there is a risk of hyperkalemia (possibly fatal) when treating patients with NYHA class II–IV heart failure and an ejection fraction of

Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid ≥ 3 g per day. A reduction in the antihypertensive effect may occur when ACE inhibitors are used concomitantly with NSAIDs, such as: acetylsalicylic acid at anti-inflammatory doses, COX-2 inhibitors, non-selective NSAIDs. Concomitant use of ACE inhibitors and NSAIDs may increase the risk of worsening renal function, including the possibility of acute renal failure, and an increase in plasma potassium, especially in patients with a history of impaired renal function. This combination should be administered with caution, particularly in elderly patients. Patients should be rehydrated and renal function monitored at the start of treatment with this combination and periodically thereafter.

Medicines, concomitant administration of which requires attention

Sympathomimetics may weaken the antihypertensive effect of ACE inhibitors.

Gold: Concomitant use of ACE inhibitors, including perindopril, and injectable gold products (sodium aurothiomalate) may rarely result in nitrate-like reactions (facial flushing, flushing, nausea, vomiting, and hypotension).

Interactions related to amlodipine

Concomitant use is not recommended.

Dantrolene (infusion). In experimental studies, fatal ventricular fibrillation and cardiovascular collapse have been observed in association with hyperkalemia following the administration of verapamil and dantrolene intravenously. Because of the potential for hyperkalemia, it is recommended that concomitant administration of calcium antagonists such as amlodipine be avoided in patients with malignant hyperthermia and in patients suspected of having malignant hyperthermia.

Medicinal products, the simultaneous use of which requires special caution

CYP3A4 inhibitors. Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may result in increased amlodipine concentrations. The clinical manifestation of the above pharmacokinetic changes may be more pronounced in elderly patients. In such cases, clinical monitoring and dose adjustment are necessary. There is an increased risk of hypotension in patients taking clarithromycin in combination with amlodipine. Close observation is recommended in such patients.

Medicines, concomitant administration of which requires attention

When amlodipine is used with other drugs with antihypertensive properties, an additive antihypertensive effect is possible.

Tacrolimus: There is a risk of increased blood levels of tacrolimus when co-administered with amlodipine. To avoid toxic effects of tacrolimus, it is necessary to monitor its blood levels and, if necessary, adjust its dose in patients who are added to amlodipine.

Mechanistic target of rapamycin (mTOR) inhibitors. mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are substrates of CYP3A. Amlodipine is a weak CYP3A inhibitor. When co-administered with mTOR inhibitors, amlodipine may increase the concentration of mTOR inhibitors.

Cyclosporine. No interaction studies have been conducted with cyclosporine and amlodipine in healthy volunteers or other subjects. The exception is renal transplant patients, in whom cyclosporine concentrations fluctuated with an average increase of 0% to 40%. In renal transplant patients receiving amlodipine and cyclosporine, cyclosporine blood levels should be monitored and the cyclosporine dose reduced if necessary.

Simvastatin: Coadministration of amlodipine in multiples of 10 mg with simvastatin 80 mg resulted in a 77% increase in simvastatin concentrations compared to simvastatin alone. Patients should limit their simvastatin dose to 20 mg daily.

Other combinations. Clinical interaction studies have shown that amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin, or warfarin.

It is not recommended to use amlodipine with grapefruit or grapefruit juice, as bioavailability may increase in some patients, leading to increased hypotensive effect.

Interactions associated with Corderia AM fixed combination

Medicinal products, the simultaneous use of which requires special caution

Baclofen enhances the antihypertensive effect. Blood pressure should be monitored and, if necessary, the dose adjusted.

Medicines, concomitant administration of which requires attention

Antihypertensive agents (such as beta-blockers) and vasodilators. Concomitant use of these agents may enhance the hypotensive effect of perindopril and amlodipine; concomitant use with nitroglycerin and other nitrates or with other vasodilators may cause a further decrease in blood pressure and should therefore be administered with caution.

Corticosteroids, tetracosactide weaken the antihypertensive effect (due to water and salt retention).

Alpha-blockers (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin) enhance the antihypertensive effect and increase the risk of orthostatic hypotension.

Amifostine may enhance the antihypertensive effect of amlodipine.

Tricyclic antidepressants/antipsychotics/anesthetics enhance the antihypertensive effect and increase the risk of orthostatic hypotension.

Application features

All precautions regarding the use of individual components of the medicinal product also apply to the fixed combination of Corderia AM.

Special precautions for use of perindopril

Hypersensitivity/angioedema: Rare cases of hypersensitivity/angioedema have been reported with the use of ACE inhibitors, including perindopril.