Co-Amlessa • presence, composition and method of application

Co-amlessa is a branded pharmaceutical drug. An antihypertensive drug, an ACE inhibitor, contains a combination of three active ingredients: perindopril, amlodipine and indapamide.

Perindopril has a hypotensive effect and is good at lowering blood pressure in hypertension. This substance also has a vasodilating effect, and it performs the function of restoring the elasticity of the arteries. Taking perindopril with thiazide-like diuretics increases the effectiveness of both substances.
Indapamide has a mechanism of action similar to thiazide diuretics. It removes sodium and chlorides with urine, and in lower concentrations - potassium and magnesium, thus increasing diuresis, due to which a hypotensive effect is observed.
Amlodipine is a calcium channel blocker that relaxes vascular smooth muscle and dilates the coronary arteries.

Hypertension is currently one of the most common chronic diseases throughout the world. Hypertensive patients are at risk of developing strokes, heart attacks, vision loss, and other dangerous diseases. The reason for this may be: excess weight, unhealthy diet, environment, concomitant diseases, heredity and many other factors. For any changes in blood pressure, specialist supervision is needed, and only a doctor can decide whether it is necessary to reduce the pressure and prescribe a drug for this. Self-medication with antihypertensive drugs can be life-threatening.

Contraindications

Susceptibility to substances included in the drug;
Angioneurotic edema (Quincke's edema), history, congenital or idiopathic;
Hepatic encephalopathy and liver disorders;
Hypokalemia;
Hypotension;
Cardiogenic shock;
Bilateral renal artery stenosis or stenosis of the artery of a single kidney;
Heart failure, poor hemodynamics after myocardial infarction;
Pregnancy and its planning period;
Breastfeeding period;
Severe renal failure (creatinine clearance <30 ml/min);
Moderate renal failure (creatinine clearance <60 ml/min);
The drug is contraindicated in children and patients on hemodialysis.

Amlessa 4 mg/5 mg No. 30 tablet.

Instructions for medical use of the drug AMLESSA® Trade name AMLESSA® International nonproprietary name No Dosage form Tablets 4 mg / 5 mg, 4 mg / 10 mg, 8 mg / 5 mg, 8 mg / 10 mg Composition One tablet contains active substances: tablets 4 mg/5 mg: perindopril erbumine 4 mg, amlodipine besylate 6.935 mg (equivalent to 5 mg amlodipine), tablets 4 mg/10 mg: perindopril erbumine 4 mg, amlodipine besilate 13.870 mg (equivalent to 10 mg amlodipine), tablets 8 mg/5 mg: perindopril erbumine 8 mg, amlodipine besylate 6.935 mg (equivalent to 5 mg amlodipine), tablets 8 mg/10 mg: perindopril erbumine 8 mg, amlodipine besylate 13.870 mg (equivalent to 10 mg amlodipine), excipients: microcrystalline cellulose, pregelatinized starch , sodium starch glycolate, calcium chloride, sodium bicarbonate, colloidal anhydrous silicon dioxide, magnesium stearate; Description Tablets are white or almost white, round, slightly biconvex, with beveled edges (for a dosage of 4 mg/5 mg) Tablets are white or almost white, capsule-shaped, biconvex, with a score on one side (for a dosage of 4 mg/10 mg) Tablets are white or almost white, round, biconvex, with beveled edges (for a dosage of 8 mg/5 mg) Tablets are white or almost white, round, biconvex, with a score on one side and beveled edges (for a dosage of 8 mg/10 mg) Pharmacotherapeutic group Drugs affecting the renin-angiotensin system, ACE inhibitors in combination with other drugs. ACE inhibitors in combination with other “slow” calcium channel blockers. Perindopril and amplodipine. ATC code C09BB04 Pharmacological properties Pharmacokinetics The pharmacokinetic parameters of perindopril and amlodipine in the composition of Amless® and when taking tablets containing one component differ slightly. Perindopril When taken orally, absorption of perindopril occurs quickly, the maximum concentration is reached within 1 hour. The half-life of perindopril in plasma is 1 hour. Perindopril is a prodrug. 27% of the administered dose of perindopril enters the bloodstream in the form of the active metabolite perindoprilate. In addition to the active perindoprilate, five more inactive metabolites are formed in the body. The maximum concentration of perindoprilate in plasma is achieved 3-4 hours after taking the drug. Eating reduces the conversion of perindopril to perindoprilat, and, consequently, its bioavailability, therefore perindopril erbumine is recommended to be taken once a day, orally, in the morning before breakfast. The relationship between the dose of perindopril and its plasma exposure is linear. The volume of distribution of unbound perindoprilate is approximately 0.2 L/kg. The binding of perindoprilate to plasma proteins is 20%. Basically, binding occurs with angiotensin-converting enzyme (ACF), but depends on the concentration of the drug. Perindoprilat is excreted in the urine, the final half-life of its free fraction is about 17 hours, which allows it to reach an equilibrium state in 4 days. The elimination of perindoprilate is slower in elderly patients, as well as in patients with cardiac or renal failure. Therefore, routine medical surveillance should include frequent monitoring of creatinine and potassium levels. During dialysis, the clearance of perindoprilate is 70 ml/min. The kinetics of perindopril changes in patients with liver cirrhosis: the hepatic clearance of the parent molecule is slowed by half. However, the amount of perindoprilate formed does not decrease, so dosage adjustment is not required. Amlodipine When taken orally in therapeutic doses, amlodipine is well absorbed, reaching maximum concentration in the blood 6-12 hours after administration. Absolute bioavailability is 64-80%. The volume of distribution is approximately 21 l/kg. Food intake does not affect the bioavailability of amlodipine. Approximately 97.5% of circulating amlodipine is bound to plasma proteins. The final half-life from plasma is 35-50 hours, which corresponds to the administration of the drug once a day. Amlodipine is largely metabolized in the liver to the formation of inactive metabolites, 60% of the dose taken is excreted in the urine, 10% as unchanged amlodipine. Use in elderly patients The time to reach the maximum concentration of amlodipine in plasma is the same in elderly and young patients. In elderly patients, the clearance of amlodipine decreases, which is accompanied by an increase in AUC and T1/2. The recommended dosage regimen for the elderly is the same, although dose increases should be done with caution. Use in patients with renal and hepatic insufficiency In patients with renal insufficiency and impaired liver function, the half-life of amlodipine slows down. Pharmacodynamics Amlessa is a combination of perindopril erbumine, an ACE inhibitor, and amlodipine, a calcium ion antagonist of the dihydropyridine group. Inhibition of ACE results in a decrease in plasma angiotensin II, which leads to an increase in plasma renin activity and a decrease in aldosterone release. Inhibition of ACE also leads to increased activity of the circulating and local kallikrein-kinin system (as well as activation of the prostaglandin system). It is possible that this mechanism contributes to the hypotensive effect of ACE inhibitors and partially causes some of the side effects (for example, cough). Perindopril acts through its active metabolite perindoprilat. Other metabolites have not shown the ability to inhibit the action of ACP. Hypertension Perindopril is effective for arterial hypertension of any degree: mild, moderate and severe; reduces systolic and diastolic blood pressure 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 increases, while the level of glomerular filtration usually remains unchanged. Maximum hypotensive activity is achieved 4-6 hours after taking a single dose and persists for at least 24 hours. The decrease in blood pressure occurs quickly. In patients susceptible to treatment, normalization of blood pressure occurs within a month and persists without the occurrence of tachyphylaxis. Discontinuation of treatment is not accompanied by the development of withdrawal syndrome. Perindopril reduces left ventricular hypertrophy. Perindopril has been confirmed to have a vasodilatory effect, improve the elasticity of large arteries and reduce the flow/lumen ratio of small arteries. Patients with stable coronary artery disease Treatment with perindopril erbumine 8 mg (equivalent to 10 mg perindopril arginine) administered once daily resulted in an absolute significant reduction in the primary endpoint of 1.9% (20% relative risk reduction). In patients with a history of myocardial infarction and/or revascularization, the absolute reduction in the primary endpoint reached 2.2%, which corresponds to a relative risk reduction (RRR) of 22.4% compared with placebo. Amlodipine is a calcium ion antagonist and slow channel blocker that blocks the entry of calcium ions through membranes into the smooth muscle cells of the myocardium and blood vessels. The mechanism of the antihypertensive effect of amlodipine is due to a direct relaxing effect on vascular smooth muscle. The exact mechanism of action of amlodipine in angina pectoris has not been fully established, but amlodipine reduces ischemia in two ways: 1) dilates peripheral arterioles and thus reduces the total peripheral resistance (afterload), which requires the work of the heart to overcome; since the heart rate remains stable, reducing the load on the heart leads to a decrease in energy consumption by the myocardium and its oxygen demand 2) dilates the main coronary arteries and coronary arterioles, while increasing the supply of oxygen to the myocardium in patients with vasospastic angina (Prinzmetal’s angina or variant angina) ). In patients with hypertension, a single daily dose of amlodipine provides a clinically significant reduction in blood pressure over 24 hours, both in the supine and standing positions. In patients with angina pectoris, a single daily dose of amlodipine increases the total time of physical activity, delays the onset of an angina attack and the development of ST segment depression (by 1 mm) during exercise, reduces the frequency of angina attacks and the consumption of nitroglycerin tablets. Amlodipine does not have any adverse effects on metabolism and plasma lipids and is suitable for the treatment of patients suffering from bronchial asthma, diabetes mellitus and gout. Indications for use - essential hypertension - stable coronary heart disease. Method of administration and dosage: For oral administration. It is advisable to take one tablet of Amlessa® in the morning, before meals, once a day. Fixed dose combination is not suitable for initial therapy. If necessary, dosage changes should be made by individual titration of the dose of the free combination of components. Amlessa® can be prescribed to patients with CC ³ 60 ml/min without dose adjustment; patients with CC < 60 ml/min are recommended to individually titrate the dose of individual components. There is no correlation between changes in plasma concentrations of amlodipine and the degree of renal dysfunction. The dosage regimen for patients with liver failure has not been established. Therefore, caution should be exercised when prescribing Amlessa®. Side effects Associated with amlodipine Common (from ≥1/100 to <1/10) - drowsiness, dizziness, headache - rapid heartbeat - hot flashes - abdominal pain, nausea - swelling, peripheral edema - fatigue Uncommon (from ≥1/1,000 up to <1/100) - weight gain or loss - insomnia, mood changes - tremor, hypesthesia, paresthesia - visual disturbances - tinnitus - fainting - hypotension (and effects associated with hypotension), shortness of breath - rhinitis - vomiting, dyspepsia, changes in intestinal motility, dry mouth, taste disturbances - alopecia, purpura, skin discoloration, increased sweating, itching, rash - arthralgia, myalgia, muscle cramps - back pain, chest pain, asthenia, malaise - urination disorders, nocturnal polyuria , increased urination - impotence, gynecomastia Rarely (from ≥1/10,000 to <1/1,000) - anginal pain Very rarely (<1/10,000) - leukopenia / neutropenia, thrombocytopenia - Quincke's edema, allergic reaction: urticaria - hyperglycemia - increased tone muscles of the wall of a hollow organ - peripheral neuropathy - myocardial infarction, possibly caused by excessive hypotension in high-risk patients - arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation) - vasculitis - cough - hypertrophic gingivitis - pancreatitis, gastritis - hepatitis, cholestatic jaundice - erythema (various types) - Stevens-Johnson syndrome (malignant exudative erythema) - increased levels of liver enzymes: AST, AST (mainly consistent with cholestasis) Isolated cases of extrapyramidal syndrome have been reported when taking calcium channel blockers. Associated with perindopril Common (≥1/100 to <1/10) - dizziness, headache - paresthesia - visual disturbances - tinnitus - hypotension (and effects associated with hypotension) - shortness of breath, cough - abdominal pain, nausea , vomiting, dyspepsia, dysgeusia, diarrhea, constipation - itching, rash - muscle cramps - asthenia Uncommon (from ≥1/1,000 to <1/100) - allergic reaction: urticaria - mood changes - sleep disturbances - bronchospasm, dry mouth - angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx - sweating - impaired renal function - impotence Rarely (≥1/10,000 to <1/1,000) - increased serum bilirubin and liver enzymes Very rarely (<1/10,000) - confusion - leukopenia/neutropenia, agranulocytosis or pancytopenia, thrombocytopenia, hemolytic anemia in patients with congenital G-6PDH deficiency, decreased hemoglobin and hematocrit - angina pectoris - stroke, possibly caused by very severe hypotension in patients of the group high risk - rhinitis - eosinophilic pneumonia - pancreatitis - hepatitis, cytolytic or cholestatic hepatitis - erythema - acute renal failure Unknown (cannot be estimated from available data) - hypokalemia - vasculitis - increased blood urea and serum creatinine, hyperkalemia Contraindications - hypersensitivity to perindopril (or any other ACE inhibitor), amlodipine (or any dihydropyridine) or to any of the excipients - history of angioedema associated with previous treatment with ACE inhibitors - hereditary or idiopathic angioedema - pregnancy and lactation - severe arterial hypotension - shock, including cardiogenic shock - left ventricular outflow tract obstruction (eg, severe aortic stenosis) - hemodynamically unstable heart failure after acute myocardial infarction Drug interactions Perindopril-related Combinations not recommended Potassium-sparing diuretics (such as spironolactone, triamterene or amiloride), potassium supplements and potassium-containing salt substitutes may lead to significant increases in serum potassium levels. If the concomitant use of these drugs is indicated due to severe hypokalemia, then extreme caution should be exercised when taking them and frequent monitoring of serum potassium levels should be performed. Combination use of lithium and ACE inhibitors may result in a reversible increase in serum lithium concentrations and toxicity (severe neurotoxicity). But if combined use is necessary, then careful monitoring of the level of lithium in the blood serum should be carried out. Estramustine increases the risk of unwanted effects of perindopril, such as angioedema (angioedema). Combinations that require special caution When taking ACE inhibitors simultaneously with non-steroidal anti-inflammatory drugs (for example, acetylsalicylic acid ³ 3 g / day and anti-inflammatory drugs, COX-2 inhibitors and non-selective NSAIDs), a decrease in the hypotensive effect may occur. Concomitant use of ACE inhibitors and NSAIDs may increase the risk of deterioration of renal function, including possible acute renal failure, increased serum potassium, especially in patients with pre-existing impaired renal function. The combination of these drugs should be prescribed with caution, especially in elderly patients. Ensure that patients are adequately hydrated. At the beginning of combination therapy, and periodically during therapy, renal function should be monitored. Prescribing ACE inhibitors to patients receiving antidiabetic drugs (insulin or hypoglycemic sulfonamides) may lead to an increased hypoglycemic effect. Hypoglycemia occurs rarely (probably improved glucose tolerance with a subsequent reduction in the need for insulin). Combinations that require caution In patients taking diuretics, especially those with reduced circulating blood volume and/or salt deficiency, an excessive decrease in blood pressure may occur after initiation of treatment with an ACE inhibitor. Discontinuation of the diuretic, increasing blood volume or taking salt before starting treatment, as well as prescribing low initial doses of perindopril and gradually increasing them reduce the risk of hypotension. Sympathomimetics may reduce the hypotensive effect of ACE inhibitors. There have been rare reports of nitrite reactions (symptoms including facial flushing, nausea, vomiting and hypotension) in patients receiving gold injection therapy (sodium aurothiomalate) and concomitant treatment with ACE inhibitors, including perindopril. Amlodipine-Related Combinations Requiring Special Caution When a CYP3A4 inhibitor was coadministered with erythromycin in younger patients and diltiazem in elderly patients, the plasma concentrations of amlodipine increased by 22% and 50%, respectively. However, the clinical significance of these results remains uncertain. It is possible that strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir) may increase plasma concentrations of amlodipine to a greater extent than diltiazem. Amlodipine should be used with caution when used with CYP3A4 inhibitors. Concomitant use of CYP3A4 inducers (rifampicin, St. John's wort, anticonvulsants, i.e. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone) may lead to a decrease in the plasma concentration of amlodipine due to an increase in the hepatic metabolism of amlodipine by these inducers. When combining amlodipine with CYP3A4 inducers, caution should be exercised; if necessary, the dosage of amlodipine can be adapted. Combinations to consider With beta blockers prescribed for heart failure (bisoprolol, carvedilol, metoprolol), the risk of hypotension and cardiac weakness increases in patients with heart failure if it is latent or uncontrolled (adding negative inotropic effect). In addition, a beta blocker may reduce the sympathetic reflex during severe hemodynamic repercussion. In monotherapy, amlodipine is safely prescribed with thiazide diuretics, beta blockers, ACE inhibitors, long-acting nitrates, sublingual nitrolycerin, digoxin, warfarin, atorvastatin, sildenafil, antacids (aluminum hydroxide gel, magnesium hydroxide, simethicone), cimetidine, non-steroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic drugs. Special studies conducted with cimetidin, atorvastatin, digoxin, warfarin and cyclosporine did not reveal changes in their pharmacokinetics and in pharmacokinetics of amlodipine. Combinations that require special caution of Baclofen enhances the severity of the hypotensive effect. With joint use, it is necessary to monitor blood pressure and renal function, as well as, if necessary, to adapt the dose of the antihypertensive drug. Combinations that alpha blockers (prazozin, alphazosin, doxasosine, tamsulosine, terasososine), beta-blockers, vasodilators, nitroglycerin and other nitrates, tricyclic antidepressants, anti -rapschotic, anesthetic, amphostin enhance the hypotensive amlodipine effect and increase the risk of an orthostostatic hypo. Tenzia. Corticosteroids, tetracosactide reduce the hypotensive effect (salt and water delay caused by the action of corticosteroids). Special instructions related to the perindopril have rare reports about the angioedema of the face, limbs, lips, mucous membranes, tongue, voice gap and/or larynx in patients undergoing AKF inhibitors, including perindopril. In such cases, AMLES® reception should immediately be stopped and the necessary monitoring until the symptoms completely disappear. Usually, in cases where the edema affected only his face and lips, it took place without any treatment, antihistamines helped alleviate the symptoms. Angioedema, which is accompanied by swelling of the larynx, can be fatal. When swelling of the tongue, voice gap or larynx, in which the obstruction of the respiratory tract is likely, should immediately provide first aid, which may include the purpose of adrenaline and/or maintaining free respiratory tract. The patient should be under close medical supervision until symptoms disappear completely and completely. An increased risk of the onset of angioedema when taking AKF inhibitor exists in patients who have undergone angioedema, not associated with the reception of AKF inhibitors. Rare messages about intestinal angiotecture in patients taking AKF inhibitors were received. These patients occurred in abdominal pain (with nausea and vomiting or without them); In some cases, the Angiootects of the face and the levels of the C-1 esterase did not precede this. The diagnosis of angiooteis was made using the procedures that included computed tomography, ultrasound or during a surgical operation, the symptoms ceased after the cessation of the ACF inhibitor. Intestinal angiootex should be included in the differential diagnosis of patients taking AKF inhibitors with abdominal pain. In rare cases, in patients undergoing LDSP AFRNP (low density lipoproteins) using dextra sulfate absorption, when the ACF inhibitors were prescribed cases of development of anaphylactoid reactions threatening the lives. It was possible to avoid these reactions by temporary cancellation of the AKF inhibitor every time before the apel. In some patients who received AKF inhibitors during desensitizing therapy (for example, hymenoperic poison), anaphylactoid reactions occurred. These reactions were able to avoid by temporary abolition of the AKF inhibitor, but they again occurred in the event of a careless administration of the drug. In patients taking AKF inhibitors, neutropenia/agranulocytosis, thrombocytopenia and anemia were observed. In patients with the normal function of the liver and the absence of other complicating factors, neutropenia rarely occurs. When taking perindopril, extreme caution should be observed for patients with collagenic-vascular diseases, patients undergoing immunosuppressant therapy, treatment with allopurinol or pro-cainamide, or those who have all these complicating factors, especially with existing impaired renal function. Some of these patients developed serious infections. In some cases, intensive therapy with antibiotics turned out to be unsuccessful. When prescribing perindopril, such patients are recommended to conduct periodic monitoring of leukocytes and instruct patients about the need to report any signs of infection (for example, sore throat, heat). Praises when taking hypotension with clinical manifestations (with a reduced volume of circulating blood: taking diuretics on a diet with limited dialysis suffering from diarrhea or vomiting; in patients with severe renin-dependent hypertension) in the treatment of ammless) in the treatment of ammless) ® should be thoroughly monitoring blood pressure, renal function and potassium levels in serum. Such considerations are applicable to patients with coronary heart disease and cerebrovascular diseases, in which a pronounced decrease in blood pressure can lead to myocardial infarction or stroke. In the case of hypotension, it is necessary to put the patient on the back and, if necessary, make up for the volume of circulating blood by intravenous administration of a 0.9% sodium chloride solution (9 mg/ml). Transfer hypotension is not a contraindication for the further administration of the drug, which can usually be continuously continued after blood pressure increased again due to an increase in the volume of circulating blood. Like other AKF inhibitors, perindopril should be prescribed with particular caution to patients with mitral valve stenosis and the obstruction of the output tract of the left ventricle, for example, with aortic stenosis or hypertrophic cardiomyopathy. During therapy, AKF inhibitors noted cases of unproductive, ongoing cough, which takes place with the abolition of the drug. A cough caused by the reception of the AKF inhibitor should be considered as part of the differential diagnosis of cough. With surgical intervention or during anesthesia, AMLES® hypotension drugs can block the formation of angiotensin II, as a result of compensatory release of renin. It is recommended to stop treatment the day before surgery. In case of hypotension, which is allegedly related to this mechanism of action, the volume of circulating blood should be increased. Some patients undergoing treatment with AKF inhibitors, including perindopril, have cases of increased potassium in blood serum. Risk factors for the development of hyperkalemia include renal failure, deterioration of renal function, age (> 70 years), diabetes mellitus, random phenomena, such as dehydration, acute heart decompensation, metabolic acidosis, simultaneous intake of potassium -saving diuretics (spironolactone, epleys, triameren or amyloride ), potassium additives or potassium -containing salt substitutes, as well as taking other drugs that cause an increase in potassium in serum (for example, heparin). Reception of potassium additives, potassium -saving diuretics and potassium -containing salt substitutes, especially patients with impaired renal function, can lead to a significant increase in the level of potassium in serum. Hyperkalemia can cause silver, sometimes fatal, arrhythmia. If the concomitant purpose of perindopril and the above drugs is considered necessary, then their intake should be carried out with caution and with regular monitoring of potassium content in blood serum. Renal failure with renal failure (creatinine clearance <60 ml/min.) An individual dose of individual components is recommended. In patients with renal failure, ordinary medical examination should include monitoring of potassium and creatinine levels. In some patients with bilateral renal arterial stenosis or stenosis of the artery of the only kidney undergoing treatment with AKF inhibitors, cases of increasing urea and creatinine in serum, which were reversible during the termination of therapy. This is most likely to occur in patients with renal failure. With renovascular hypertension, there is also an increased risk of severe hypotension and renal failure. In some patients with hypertension, without a visible violation of the vessels of the kidneys, there was an increase in the concentration of urea in the blood and creatinine in serum, it was usually insignificant and transient, especially with a combined use of perindopril and diuretic. This is most likely in patients already suffering from renal failure. In rare cases, liver failure in rare cases, the intake of AKF was accompanied by a syndrome, which begins with cholestatic jaundice and progresses in the fulminant necrosis of the liver and (sometimes) ends death. The mechanism of this syndrome is still incomprehensible. Patients receiving AKF inhibitors, in which jaundice develops or the level of liver enzymes, should stop taking the ACE inhibitor and undergo a thorough medical examination. Patients with diabetes mellitus for patients with diabetes taking oral antidiabetic drugs or insulin, during the first month of treatment with ACF inhibitor, careful monitoring of glycemia should be carried out. The race of angioedemic edema in the treatment of AKF inhibitors is more often in the patients of the black race than in patients of other races. Like other AKF inhibitors, hypotension effectively

Co-amlessa side effects

Dizziness, vertigo, ringing in the ears, visual disturbances, cough, shortness of breath, nausea, vomiting, headache, constipation, diarrhea, skin rash, itching, swelling, fatigue, convulsions, increased bilirubin in the blood serum. Cardiovascular system disorders do not often occur: angina pectoris, myocardial infarction, tachycardia.

Medicines from pharmacies are dispensed only with a doctor's prescription. It is necessary to follow the recommendations for storing the drug - at a temperature not exceeding 30°C and out of the reach of children.

Interaction

You cannot take Co-Amlessa with potassium-sparing drugs and potassium salts; taking them together provokes hyperkalemia, which can be fatal. Patients with renal failure are at high risk.

Taking ACE inhibitors together with NSAIDs reduces kidney function.

It is not recommended to take the drug with angiotensin receptor antagonists and cyclosporine, as such interaction increases the risk of hyperkalemia.

If the patient is already taking diuretics, at the beginning of therapy with Co-amlessa, an excessive decrease in blood pressure may occur and insufficiency of electrolytes/water in the body may occur.

Instructions for use CO-AMLESSA®

All instructions related to each component separately also apply to the fixed combination of the drug Co-Amlessa.

Lithium

Concomitant use of lithium and the combination of perindopril/indapamide is generally not recommended.

Double blockade of the RAAS

Dual blockade of the RAAS is associated with an increased risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy. Dual blockade of the RAAS using ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended.

In cases where combined use is absolutely indicated, careful medical supervision and mandatory monitoring of renal function, water and electrolyte balance and blood pressure are necessary.

ACE inhibitors and angiotensin II receptor antagonists should not be coadministered to patients with diabetic nephropathy.

Potassium-sparing diuretics, potassium salts

The combined use of perindopril and potassium-sparing diuretics, as well as potassium salts, is not recommended.

Neutropenia/agranulocytosis

In patients receiving ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia and anemia may develop. Neutropenia is rare in patients with normal renal function and no other complications. Perindopril should be prescribed with extreme caution to patients with collagen diseases using immunosuppressive treatment, treatment with allopurinol or procainamide, especially with pre-existing renal impairment. These patients may develop serious infections that, in some cases, do not respond to intensive antibiotic therapy. If perindopril is prescribed, it is recommended to periodically monitor the white blood cell count; patients should be informed that if any signs of an infectious disease appear (sore throat, fever), they should immediately consult a doctor.

Hypersensitivity/angioedema

Rare cases of angioedema of the face, extremities, lips, tongue, pharynx and/or larynx have been reported in patients treated with ACE inhibitors, including perindopril. These conditions can develop at any time during therapy. In such cases, you should immediately stop taking the drug and establish appropriate monitoring of the patient's condition until the complete disappearance of symptoms is confirmed. In cases where swelling affects only the face and lips, its symptoms usually resolve without special treatment, but antihistamines may be used to relieve symptoms. Angioedema, accompanied by swelling of the larynx, can be fatal. If swelling is detected in the area of the tongue, pharynx or larynx, which may lead to airway obstruction, appropriate therapy should be immediately prescribed, including subcutaneous administration of epinephrine solution 1:

1000 (0.3-0.5 ml), and/or measures have been taken to ensure airway patency.

A higher incidence of angioedema has been established in black patients receiving ACE inhibitors.

Patients with a history of angioedema that is not associated with ACE inhibitor therapy may be at increased risk of developing angioedema while taking drugs of this class.

There are rare cases of the development of angioedema of the intestine during therapy with ACE inhibitors. Patients experienced abdominal pain (sometimes with nausea or vomiting); in some cases this was not preceded by angioedema of the face, the level of C-1 esterases was normal. Angioedema was diagnosed through procedures including abdominal CT or ultrasound or during surgery; the symptoms disappeared after stopping the ACE inhibitor. These phenomena should be taken into account when carrying out differential diagnosis of patients receiving ACE inhibitors and admitted with abdominal pain.

Anaphylactoid reactions during desensitization

There are isolated reports of the development of a persistent, life-threatening anaphylactoid reaction in patients taking ACE inhibitors during desensitizing therapy with hymenoptera venom (bees, wasps). ACE inhibitors should be prescribed with caution to patients prone to allergic reactions and undergoing desensitization; Prescribing the drug to patients undergoing antidote immunotherapy should be avoided. In cases where a patient requires both treatment with ACE inhibitors and desensitization, the onset of such reactions can be prevented by temporarily discontinuing the ACE inhibitor at least 24 hours before starting the course of desensitization therapy.

Anaphylactoid reactions during LDL apheresis

Rare cases of life-threatening anaphylactoid reactions have been reported in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. The occurrence of such reactions can be prevented by temporarily stopping the use of ACE inhibitors before each LDL apheresis procedure.

Hemodialysis

There are known cases of anaphylactoid reactions in patients undergoing hemodialysis using high-flux density membranes (for example, AN69®) and simultaneously being treated with ACE inhibitors. Such patients should be prescribed either a different type of dialysis membrane or a different class of antihypertensive drugs.

Hepatic encephalopathy

In case of impaired liver function, the use of thiazide and thiazide-like diuretics can cause hepatic encephalopathy; in this case, the use of diuretics should be stopped immediately.

Photosensitivity

There are known cases of photosensitivity reactions occurring while taking thiazide and thiazide-like diuretics; in this case, it is recommended to stop taking the drug. When re-prescribing diuretics, exposed skin should be protected from direct exposure to sunlight or artificial UV radiation.

Renal dysfunction

The use of the drug is contraindicated in patients with severe renal impairment (creatinine clearance <30 ml/min). Dosages containing 8 mg/2.5 mg perindopril/indapamide (eg, 8 mg/5 mg/2.5 mg and 8 mg/10 mg/2.5 mg tablets) are contraindicated in patients with moderate renal impairment (creatinine clearance <60 ml/min).

Treatment should also be discontinued if laboratory blood tests reveal functional renal failure in a patient with arterial hypertension without previous significant renal impairment. Therapy can be resumed either at a lower dosage or with only one of the components.

Routine medical examination of such patients should include frequent monitoring of potassium and creatinine levels according to the following schedule:

the first time - after 2 weeks of treatment, then - every 2 months during the period of therapeutic stability.

Renal failure has been reported primarily in patients with severe heart failure or pre-existing renal failure, including renal artery stenosis.

This drug is generally not recommended for patients with bilateral renal artery stenosis or patients with one functioning kidney.

Risk of arterial hypotension and/or renal failure (including in case of heart failure, water-salt imbalance).

With a significant loss of water and electrolytes (strict salt-free diet or long-term treatment with diuretics), especially in patients with initially low blood pressure, with renal artery stenosis, chronic heart failure or cirrhosis of the liver, accompanied by edema and ascites, pronounced stimulation of the RAAS occurs. Consequently, inhibition of this system when taking ACE inhibitors can cause (most likely when the drug is first taken or during the first 2 weeks of treatment) a sharp drop in blood pressure and/or an increase in plasma creatinine, indicating functional renal failure. In rare cases, these symptoms may develop acutely and vary in time before they begin. In such cases, treatment can be resumed with a lower dose, with its gradual increase. In patients with coronary artery disease or cerebrovascular disease, an excessive decrease in blood pressure can lead to myocardial infarction or cerebrovascular complications.

Thiazide and thiazide-like diuretics are most effective in cases where renal function is normal or slightly impaired (for adult patients, the creatinine concentration is below approximately 25 mg/l, i.e. 220 µmol/l). In elderly patients, plasma creatinine levels should be adjusted taking into account the age, body weight and gender of the patient using the Cockroft formula:

For men:

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For women:

the calculation result should be multiplied by 0.85.

At the beginning of treatment, hypovolemia caused by loss of water and sodium while taking diuretics may lead to a decrease in GFR and be accompanied by an increase in plasma creatinine and urea concentrations. This transient functional renal failure has no adverse consequences in patients with normal renal function, but may worsen existing renal failure.

Routine medical examination of such patients should include frequent monitoring of potassium and creatinine levels according to the following schedule:

the first time - after 2 weeks of treatment, then - every 2 months during the period of therapeutic stability.

Changes in plasma concentrations of amlodipine do not correlate with the degree of renal dysfunction. Amlodipine can be used in normal doses to treat such patients.

The effect of Co-Amlessa has not been studied in patients with impaired renal function. The properties of each individual component of this combination should be taken into account.

Arterial hypotension and water-electrolyte imbalance

When sodium levels are low, especially in patients with pre-existing low blood pressure, renal artery stenosis, congestive heart failure, or cirrhosis with edema and ascites, there is a risk of sudden hypotension. Systematic monitoring should be carried out to identify clinical signs of deficiency in the body of water or electrolytes, for example, after diarrhea or vomiting. In such patients, it is necessary to regularly determine the content of electrolytes in plasma.

In case of severe arterial hypotension, intravenous administration of an isotonic solution may be necessary. Transient arterial hypotension is not a contraindication for continued treatment. After restoration of satisfactory blood volume and blood pressure, treatment can be resumed either with a lower dosage of the drug or with only one of its components.

Taking any diuretic drugs can lead to a decrease in sodium levels in the blood plasma, which, in turn, contributes to the development of a number of serious complications. Initially, a decrease in sodium levels may be asymptomatic, which is why regular monitoring is necessary. In elderly patients and in patients with cirrhosis, monitoring should be performed even more frequently.

Potassium content

The combination of indapamide, perindopril and amlodipine does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or in patients with renal failure. As with any other antihypertensive drug used in combination with a diuretic, regular monitoring of plasma potassium levels should be carried out.

In some patients treated with ACE inhibitors, including perindopril, cases of increased serum potassium levels have been reported. Risk factors for hyperkalemia include renal failure, deterioration of renal function, age >70 years, diabetes mellitus, certain concomitant conditions (decrease in blood volume, acute heart failure, metabolic acidosis, concomitant use of potassium-sparing diuretics, for example, spironolactone, eplerenone, triamterene or amiloride), and also potassium preparations or potassium-containing salt substitutes. The risk group also includes patients taking other drugs that increase serum potassium levels (for example, heparin). Hyperkalemia can cause serious heart rhythm problems, sometimes fatal. If the concomitant administration of the above-mentioned drugs is considered necessary, then their use should be carried out with regular monitoring of serum potassium levels.

The greatest risk when taking thiazide and thiazide-like diuretics is hypokalemia. In order to prevent hypokalemia (<3.4 mmol/l), special attention should be paid to persons at high risk:

elderly and/or malnourished patients, regardless of whether they are taking other medications;
patients with liver cirrhosis, which is accompanied by edema and ascites;
patients with coronary artery disease and heart failure. In such cases, hypokalemia increases the toxicity of cardiac glycosides and increases the risk of arrhythmia.

The high-risk group also includes patients with an increased QT interval on the ECG, regardless of the etiology of the disease. Hypokalemia, as well as bradycardia, is a predisposing factor in the development of serious cardiac arrhythmias, especially torsades de pointes, which can be fatal.

In all the described cases, more frequent monitoring of potassium concentration in the blood plasma is required - the first determination of this indicator should be carried out during the 1st week of treatment. If low potassium levels are detected, correction is required.

Calcium content

Thiazide and thiazide-like diuretics may reduce urinary calcium excretion, leading to a slight and temporary increase in plasma calcium levels. A significant increase in calcium levels may be a consequence of hidden hyperparathyroidism. In this case, treatment should be stopped until the function of the parathyroid glands is examined.

Renovascular hypertension

Renovascular hypertension is treated by revascularization. However, the use of ACE inhibitors may be beneficial in patients with renovascular hypertension awaiting surgery or in whom surgery is not feasible.

When prescribing the drug to patients with established or suspected renal artery stenosis, treatment should be started with low doses in a hospital setting, and monitoring of renal function and potassium levels is necessary, because Some patients developed functional renal failure, reversible after discontinuation of the drug. Dosages of 8 mg/5 mg/2.5 mg and 8 mg/10 mg/2.5 mg are not recommended for this category of patients.

Atherosclerosis

The risk of arterial hypotension exists in all patients, but special caution must be observed in patients with coronary artery disease or cerebrovascular insufficiency. Treatment should begin with low doses.

Hypertensive crisis

The safety and effectiveness of amlodipine in hypertensive crisis have not been established.

Heart failure

The drug should be used with caution in patients with heart failure. In patients with severe heart failure (class IV), treatment should be started under medical supervision and at lower doses. The use of beta-blockers should not be discontinued in patients with arterial hypertension and coronary insufficiency:

ACE inhibitors should be added to the beta-blocker therapy regimen.

In a long-term placebo-controlled study in patients with severe heart failure (NYHA functional classes III and IV), the incidence of pulmonary edema was higher in the amlodipine group than in the placebo group. Calcium channel blockers, incl. amlodipine should be used with caution in patients with congestive heart failure as there may be an increased risk of cardiovascular complications and mortality.

Aortic or mitral valve stenosis/hypertrophic cardiomyopathy

Caution should be exercised when using ACE inhibitors in patients with left ventricular outflow tract obstruction.

Patients with diabetes mellitus

In patients with insulin-dependent diabetes mellitus (risk of spontaneous increases in potassium levels), treatment should begin with low doses and under medical supervision. In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be regularly monitored during the 1st month of ACE inhibitor therapy.

Cough

During therapy with ACE inhibitors, a dry cough may develop, which is persistent and disappears after discontinuation of the drug. This symptom may have an iatrogenic etiology. If an ACE inhibitor is preferred, continued treatment should be considered.

Ethnic characteristics

Perindopril (like other ACE inhibitors) has a less pronounced hypotensive effect in patients of the Black race compared to representatives of other races, possibly due to the higher prevalence of low-renin conditions in this category of patients suffering from arterial hypertension.

Surgery/anesthesia

ACE inhibitors may cause a drop in blood pressure during anesthesia, especially if the anesthetic used has a hypotensive effect. Therefore, it is recommended that treatment with long-acting ACE inhibitors, such as perindopril, be stopped, if possible, 1 day before surgery.

Liver failure

In rare cases, ACE inhibitor therapy has been associated with a syndrome that begins with cholestatic jaundice, progresses to fulminant hepatic necrosis, and (sometimes) ends in death. The mechanism of this syndrome is unknown. Patients receiving ACE inhibitors who develop jaundice or significantly elevated liver enzyme levels should stop taking the ACE inhibitor and undergo medical evaluation.

In patients with impaired liver function, amlodipine T1/2 is prolonged and AUC values are increased; Dosing recommendations have not been established. However, it is recommended to start treatment with low doses of amlodipine; caution should be exercised when starting therapy and when increasing doses. When using the drug in patients with severe hepatic impairment, slow dose titration and close medical monitoring may be required.

The effect of Co-Amlessa has not been studied in patients with impaired liver function. Considering the properties of each individual component of this combination, the drug is contraindicated in patients with severe liver dysfunction; caution should be exercised in patients with mild to moderate liver failure.

Uric acid

In patients with hyperuricemia, the frequency of exacerbations of gout attacks may increase.

Elderly patients

Renal function and potassium levels should be assessed before starting treatment. To avoid a sharp decrease in blood pressure, the initial dose of the drug is selected depending on the hypotensive effect, especially in cases of sodium deficiency. Caution should be exercised when increasing doses of amlodipine in this category of patients.

Use in pediatrics

Efficacy and tolerability of the drug in children and adolescents

not installed.

Impact on the ability to drive vehicles and operate machinery

Studies on the effect of the drug on the ability to drive vehicles or operate machinery have not been conducted.

Perindopril and indapamide do not directly affect the ability to drive a car or operate potentially dangerous machinery. However, in some patients they may cause individual reactions associated with a decrease in blood pressure. Amlodipine has a minor effect on the ability to drive a car and operate potentially dangerous machinery. In patients who experience dizziness, headache, fatigue, weakness or nausea, the speed of psychomotor reactions, and, as a result, the ability to drive or operate machinery may be reduced. Caution should be exercised, especially at the beginning of treatment.

Co-amlessa tablets 8mg/5mg/2.5mg No. 10x3

Name

Co-amlessa tab. 8 mg 5 mg 2.5 mg per blister. per pack №10x3

Description

Tablets 2 mg + 5 mg + 0.625 mg: white or almost white, oval, biconvex, with a score on one side of the tablet. The score is intended solely to facilitate swallowing and does not ensure that the tablet is divided into equal parts. Tablets 4 mg + 5 mg + 1.25 mg: white or almost white, round, slightly biconvex tablets with beveled edges. Tablets 4 mg + 10 mg + 1.25 mg: white or almost white, oval, biconvex, with a score on one side of the tablet. The tablet can be divided into equal parts. Tablets 8 mg + 5 mg + 2.5 mg: white or almost white, round, biconvex tablets. Tablets 8 mg + 10 mg + 2.5 mg: white or almost white, round, biconvex, with a score on one side of the tablet. The tablet can be divided into equal parts.

Main active ingredient

Perindopril+indapamide+amlodipine

Release form

Pills

Dosage

8 mg + 10 mg + 2.5 mg

special instructions

All instructions related to each component separately also apply to the fixed Co-Amless combination. Special warnings Lithium Concomitant use of lithium and the combination of perindopril/indapamide is usually not recommended. Dual blockade of the renin-angiotensin-aldosterone system Dual blockade of the renin-angiotensin-aldosterone system is associated with an increased risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy. Dual blockade of the RAAS using ACE inhibitors, angiotensin II receptor blockers (ARBs) or aliskiren cannot be recommended. In cases where combined use is absolutely indicated, careful supervision by a specialist and mandatory monitoring of renal function, water and electrolyte balance and blood pressure are necessary. ACE inhibitors and angiotensin II receptor blockers should not be coadministered to patients with diabetic nephropathy. Potassium-sparing diuretics, potassium salts The combined use of perindopril and potassium-sparing diuretics, as well as potassium salts, is not recommended. Neutropenia/agranulocytosis In patients receiving ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia and anemia may develop. Neutropenia is rare in patients with normal renal function and no other complications. Perindopril should be prescribed with extreme caution to patients with collagen diseases using immunosuppressive treatment, treatment with allopurinol or procainamide, especially with pre-existing impairment of renal function. These patients may develop serious infections that, in some cases, do not respond to intensive antibiotic therapy. If perindopril is prescribed, it is recommended to periodically monitor the white blood cell count; patients should be informed that if any signs of an infectious disease appear (sore throat, fever), they should immediately consult a doctor. Hypersensitivity/angioedema Rare cases of angioedema of the face, extremities, lips, tongue, pharynx and/or larynx have been reported in patients treated with ACE inhibitors, including perindopril. These conditions can develop at any time during therapy. In such cases, you should immediately stop taking the drug and establish appropriate monitoring of the patient's condition until the complete disappearance of symptoms is confirmed. In cases where swelling affects only the face and lips, its symptoms usually go away without special treatment, however, antihistamines can be used to relieve symptoms. Angioedema, accompanied by swelling of the larynx, can be fatal. If swelling is detected in the area of the tongue, pharynx or larynx, which may lead to airway obstruction, appropriate therapy should be immediately prescribed, including subcutaneous administration of a solution of epinephrine 1:1000 (0.3 ml - 0.5 ml), and/or measures have been taken to ensure airway patency. A higher incidence of angioedema has been established in black patients receiving ACE inhibitors. Patients with a history of angioedema that is not associated with ACE inhibitor therapy may be at increased risk of developing angioedema while taking drugs of this class. There are rare cases of the development of intestinal vascular edema during therapy with ACE inhibitors. Patients experienced abdominal pain (sometimes with nausea or vomiting); in some cases this was not preceded by facial angioedema and C-1 esterase levels were normal. Angioedema was diagnosed through procedures including abdominal computed tomography, ultrasound, or surgery; the symptoms disappeared after stopping the ACE inhibitor. These phenomena should be taken into account when carrying out differential diagnosis of patients receiving ACE inhibitors and admitted with abdominal pain. Anaphylactoid reactions during desensitization There are isolated reports of the development of a persistent, life-threatening anaphylactoid reaction in patients taking ACE inhibitors during desensitizing therapy with hymenoptera venom (bees, wasps). ACE inhibitors should be prescribed with caution to patients prone to allergic reactions and undergoing desensitization; Prescribing the drug to patients undergoing antidote immunotherapy should be avoided. In cases where a patient requires both treatment with ACE inhibitors and desensitization, the onset of such reactions can be prevented by temporarily discontinuing the ACE inhibitor at least 24 hours before starting the course of desensitization therapy. Anaphylactoid reactions during LDL apheresis (low-density lipoprotein apheresis) Rare cases of life-threatening anaphylactoid reactions have been reported in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. The occurrence of such reactions can be prevented by temporarily stopping the use of ACE inhibitors before each apheresis procedure JI11H11. Hemodialysis There are known cases of anaphylactoid reactions in patients undergoing hemodialysis using high-flux density membranes (for example, AN 69®) and simultaneously being treated with ACE inhibitors. Such patients should be prescribed either a different type of dialysis membrane or a different class of antihypertensive drugs. Hepatic encephalopathy In case of impaired liver function, the use of thiazide and thiazide-like diuretics can cause hepatic encephalopathy; in this case, the use of diuretics should be stopped immediately. Photosensitivity There are known cases of photosensitivity reactions occurring while taking thiazide and thiazide-like diuretics; in this case, it is recommended to stop taking the drug. When re-prescribing diuretics, exposed skin should be protected from direct exposure to sunlight or artificial UV radiation.

pharmachologic effect

Co-Amlessa is a combination antihypertensive drug containing three active components with a complementary mechanism for controlling blood pressure in patients with hypertension. Perindopril erbumine (perindopril mpem-butylamine) is an angiotensin-converting enzyme inhibitor (ACE inhibitor), indapamide is a chlorosulfamoyl diuretic, and amlodipine is a calcium ion antagonist. The pharmacological effect of the drug is due to the properties of each of these components, taken separately, as well as the additive synergistic effect of the three components when combined.

Indications for use

Co-Amlessa is indicated for the treatment of arterial hypertension in patients who control their blood pressure using a fixed combination of perindopril/indapamide while taking amlodipine in the same dosages.

Directions for use and doses

Dosage Take 1 tablet 1 time per day as a single dose, preferably in the morning before meals. The fixed dose combination is not intended for initiation of therapy. Patients with impaired renal function The use of the drug is contraindicated in patients with severe renal failure (creatinine clearance (Clcr) below 30 ml/min). Dosages of 8 mg/5 mg/2.5 mg and 8 mg/10 mg/2.5 mg are contraindicated in patients with moderate renal impairment (creatinine clearance 30 - 60 ml/min). For such patients, individual selection of doses of each component is recommended. Routine medical monitoring should include frequent monitoring of creatinine and potassium levels. Patients with renal failure (glomerular filtration rate (GFR)

Use during pregnancy and lactation

Pregnancy Considering the influence of each component separately, the drug is not recommended in the first trimester of pregnancy. The drug is contraindicated in the second and third trimesters of pregnancy. The drug is contraindicated during lactation. A decision should be made either to stop breastfeeding or to suspend treatment, taking into account the need for this therapy for the mother. Perindopril The use of ACE inhibitors is not recommended in the first trimester of pregnancy. The use of ACE inhibitors is contraindicated in the second and third trimesters of pregnancy. Epidemiological data on the risk of teratogenicity when taking ACE inhibitors in the first trimester of pregnancy do not allow us to make a final conclusion, but a slight increase in risk cannot be excluded. Except in cases where it is impossible to replace ACE inhibitors with other alternative therapy, patients planning pregnancy should be switched to therapy with drugs whose safety profile for pregnant women is well studied. If pregnancy occurs, the ACE inhibitor should be discontinued immediately, and other therapy should be prescribed if necessary. When using ACE inhibitors in the second and third trimesters of pregnancy, fetotoxic effects (impaired renal function, oligohydroamniosis, delayed ossification of the skull bones) and neonatal toxicity (renal failure, hypotension, hyperkalemia) have been established. If you have been taking an ACE inhibitor since the second trimester of pregnancy, it is recommended to conduct an ultrasound examination of the function of the kidneys and skull bones. In newborns whose mothers took ACE inhibitors, blood pressure must be carefully monitored to prevent the possible development of hypotension. Indapamide Long-term use of thiazide diuretics in the third trimester of pregnancy can lead to a reduction in maternal plasma volume, as well as a decrease in uteroplacental blood flow, which can cause fetoplacental ischemia and fetal growth restriction. In addition, there are rare cases of hypoglycemia and thrombocytopenia in newborns when taking diuretics shortly before birth. Amlodipine The safety of amlodipine in pregnant women has not been established. In animal studies, reproductive toxicity has been demonstrated at high doses. Lactation The drug is contraindicated during lactation. A decision should be made either to stop breastfeeding or to suspend treatment, taking into account the need for this therapy for the mother. Perindopril Because There are no data on the use of perindopril during lactation, so the drug is not recommended for this category of patients. An alternative treatment with an established safety profile should be considered, especially when feeding neonates or premature infants. Indapamide Excreted in breast milk. In terms of pharmacological properties, indapamide is close to thiazide diuretics, which, in turn, when taken during breastfeeding, can lead to a decrease in the amount of breast milk or suppress lactation. Hypersensitivity reactions to sulfonamide derivatives, hypokalemia and nuclear jaundice are possible. Amlodipine It is not known whether amlodipine is excreted into breast milk. Effect on the reproductive system Perindopril and indapamide Reproductive toxicity studies showed no effect on the reproductive function of female and male rats. No impact on human reproductive function is expected. Amlodipine In some patients treated with calcium channel blockers, reversible biochemical changes in the head of the sperm have been reported. Clinical data regarding the potential effects of amlodipine on reproductive function are insufficient. One study reported reproductive side effects in male rats.

Precautionary measures

Impaired renal function The use of the drug is contraindicated in patients with severely impaired renal function (creatinine clearance 70 years, diabetes mellitus, some concomitant conditions (decrease in blood volume, acute heart failure, metabolic acidosis, concomitant use of potassium-sparing diuretics, for example, spironolactone, eplerenone, triamterene or amiloride ), as well as potassium supplements or potassium-containing salt substitutes. Patients taking other drugs that increase serum potassium levels (eg, heparin) are also at risk. Hyperkalemia can lead to serious heart rhythm disturbances, sometimes fatal. If concomitant administration of the above-mentioned drugs is considered necessary, then their use should be carried out with regular monitoring of serum potassium levels.The greatest risk when taking thiazide and thiazide-like diuretics is hypokalemia. Particular attention is paid to the prevention of hypokalemia (

Interaction with other drugs

Drug-induced hyperkalemia Certain drugs may increase the likelihood of developing hyperkalemia: aliskiren, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, heparin, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim. The combination of these drugs increases the risk of hyperkalemia. Concomitant use of Aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency: there is an increased risk of hyperkalemia, deterioration of renal function, cardiovascular morbidity and mortality. Concomitant use is not recommended Perindopril / indapamide Lithium Cases of reversible increases in serum lithium concentrations and toxicity have been reported with the simultaneous use of lithium and ACE inhibitors. Concomitant use of thiazide diuretics with ACE inhibitors may increase lithium levels and increase the risk of lithium toxicity. The use of perindopril in combination with indapamide and lithium is not recommended, but if this is still necessary, then careful monitoring of serum lithium levels should be carried out. Perindopril Aliskiren In patients, incl. Without diabetes mellitus or a history of renal failure, there is a risk of hyperkalemia, worsening renal function, cardiovascular morbidity and mortality. Concomitant use of ACE inhibitors and angiotensin II receptor blockers Clinical trial results have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher incidence of side effects such as hypotension , hyperkalemia and renal dysfunction (including acute renal failure), compared with monotherapy. Potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes Hyperkalemia may occur (potentially fatal), particularly in patients with renal impairment (additive hyperkalemic effect). Combinations of perindopril with the drugs listed above are not recommended. If coadministration is indicated, caution should be exercised and frequent monitoring of serum potassium levels should be performed. For the use of spironolactone in patients with heart failure, see the section “Concomitant use requiring special caution.” Estramustine Risk of increased adverse effects such as angioedema (angioedema). Amlodipine Dantrolene (infusion) Cardiovascular failure and fatal ventricular fibrillation, accompanied by hyperkalemia, were observed in animals after intravenous administration of verapamil and dantrolene. Due to the potential for hyperkalemia, it is recommended to avoid concomitant use of calcium channel blockers such as amlodipine in patients at risk of developing malignant hyperthermia or when treating malignant hyperthermia. Grapefruit juice It is not recommended to take amlodipine simultaneously with grapefruit juice or grapefruit, as the blood pressure lowering effect may be enhanced due to increased bioavailability. Concomitant use requiring special caution Perindopril / indapamide Baclofen Potentiation of the antihypertensive effect. Blood pressure and renal function should be monitored and the dose of the antihypertensive agent adjusted if necessary. Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid in high doses The simultaneous use of ACE inhibitors with non-steroidal anti-inflammatory drugs (acetylsalicylic acid in doses that have an anti-inflammatory effect, COX-2 inhibitors and non-selective NSAIDs) may cause a decrease in the hypotensive effect of ACE inhibitors. The simultaneous use of these drugs also increases the risk of renal impairment, including the development of acute renal failure and an increase in serum potassium, especially in patients with pre-existing renal impairment. This combination should be prescribed with caution, especially in the elderly. Patients should receive sufficient fluids, and it is recommended that renal function be monitored before and periodically after starting treatment. Perindopril Antidiabetic drugs (insulin, oral hypoglycemic agents) Epidemiological studies suggest that concomitant use of ACE inhibitors and antidiabetic drugs (insulin, oral hypoglycemic agents) may cause or enhance the hypoglycemic effect with a risk of hypoglycemia, which is most likely in patients with renal insufficiency and in the first weeks of therapy. Non-potassium-sparing diuretics Patients taking diuretics, especially those with hypovolemia and/or salt deficiency, may experience an excessive decrease in blood pressure when starting to take ACE inhibitors. The risk of hypotension can be reduced by discontinuing the diuretic, increasing fluid or salt intake before starting treatment, and prescribing low initial doses of perindopril and then increasing them. In case of arterial hypertension, when hypovolemia and/or salt deficiency are possible due to taking a diuretic, the possibility of either discontinuing the diuretic before starting an ACE inhibitor and then reintroducing it, or starting ACE inhibitor therapy with lower doses and then increasing it, should be considered. In patients with chronic heart failure receiving diuretic therapy, the ACE inhibitor should be prescribed at a very low dose, if possible after reducing the diuretic dose. In all cases, renal function (creatinine levels) should be monitored during the first weeks of ACE inhibitor therapy. Potassium-sparing diuretics (eplerenone, spironolactone) Eplerenone or spironolactone in doses of 12.5 mg - 50 mg / day and ACE inhibitor in low doses: in patients with heart failure (NYHA functional classes II-IV) with ejection fraction

Note!

The description of the drug Co-Amlessa on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.

Amlessa tab. 8mg/5mg per blister. in pack No. 10x3 (perindopril + amlodipine)