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.

Co-Amlessa 4 mg/5 mg/1.25 mg No. 30 tablet.

APPROVED by the Order of the Chairman of the Committee for Control of Medical and Pharmaceutical Activities of the Ministry of Health and Social Development of the Republic of Kazakhstan Instructions for the medical use of the drug Co-Amlessa Trade name Co-Amlessa International nonproprietary name No Dosage form Tablets, 2 mg/5 mg/0.625 mg, 4 mg/ 5 mg/1.25 mg, 4 mg/10 mg/1.25 mg, 8 mg/5 mg/2.5 mg and 8 mg/10 mg/2.5 mg Composition One tablet contains the active substances: 2 mg tablets /5 mg/0.625 mg: perindopril erbumine 2 mg amlodipine besilate 6.935 mg (equivalent to amlodipine 5 mg), indapamide 0.625 mg Tablets 4 mg/5 mg/1.25 mg: perindopril erbumine 4 mg amlodipine besylate 6.935 mg (equivalent to amlodipine 5 mg ), indapamide 1.250 mg Tablets 4 mg/10 mg/1.25 mg: perindopril erbumine 4 mg, amlodipine besylate 13.870 mg (equivalent to amlodipine 10 mg), indapamide 1.250 mg Tablets 8 mg/5 mg/2.5 mg: perindopril erbumine 8 mg, amlodipine besylate 6.935 mg, (equivalent to amlodipine 5 mg) indapamide 2.5 mg Tablets 8 mg/10 mg/2.5 mg: perindopril erbumine 8 mg, amlodipine besylate 13.870 mg, (equivalent to amlodipine 10 mg) indapamide 2, 5 mg excipients: microcrystalline cellulose type 200, microcrystalline cellulose type 112, pregelatinized starch type 1500, sodium starch glycolate, calcium chloride hexahydrate, sodium bicarbonate, colloidal anhydrous silicon dioxide, magnesium stearate Description Oval tablets, white to almost white in color, biconvex, with a notch on one side, 9 mm long (for a dosage of 2 mg/5 mg/0.625 mg). Tablets are round, white to almost white, slightly biconvex, chamfered, with a diameter of 7 mm (for a dosage of 4 mg/5 mg/1.25 mg). The tablets are oval, white to almost white, biconvex, scored on one side, 12 mm long (for dosage 4 mg/10 mg/1.25 mg). Tablets are round, white to almost white, biconvex, chamfered, with a diameter of 9 mm (for a dosage of 8 mg/5 mg/2.5 mg). Tablets are round in shape, from white to almost white, biconvex, scored on one side, chamfered, with a diameter of 9 mm (for a dosage of 8 mg/10 mg/2.5 mg). Pharmacotherapeutic group Drugs affecting the renin-angiotensin system. Angiotensin-converting enzyme (ACE) inhibitors. ACE inhibitors in combination with other drugs. ATC code C09BX01 Pharmacological properties Pharmacokinetics of Perindopril When taken orally, perindopril is absorbed quickly, the maximum concentration (Cmax) is reached within 1 hour. The plasma half-life 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. Cmax of perindoprilat in plasma is achieved 3-4 hours after taking the drug. Eating reduces the conversion of perindopril to perindoprilat, and therefore 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 and no dose adjustment is required. Indapamide Indapamide is quickly and completely absorbed from the gastrointestinal tract. Peak plasma concentrations in humans are achieved approximately one hour after oral administration. Plasma protein binding is 79%. The half-life (T1/2) is 14–24 hours (average 18 hours). Repeated use does not lead to accumulation. Indapamide is excreted mainly in urine (70% of the dose) and feces (22%) in the form of inactive metabolites. In patients with renal failure, the pharmacokinetic parameters of indapamide do not change. Amlodipine When taken orally in therapeutic doses, amlodipine is well absorbed, Cmax is achieved 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. T1/2 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. The time to reach Cmax 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. In patients with impaired liver function, the half-life of amlodipine slows down. Pharmacodynamics Co-Amless is a combination of perindopril erbumine - an ACE inhibitor, indapamide - a chlorosulfonamide diuretic and amlodipine - 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. Mechanism of action and pharmacodynamic effects Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (AKF), a vasoconstrictor. In addition, the enzyme stimulates the production of aldosterone by the adrenal cortex and the degradation of bradykinin, a vasodilator, into inactive heptapeptides. As a result, there is: - a decrease in aldosterone production - an increase in plasma renin activity, since aldosterone does not enhance negative feedback - a decrease in total peripheral vascular resistance with a predominant effect on the vascular bed of muscles and kidneys during long-term treatment; in this case, there is no retention of salts and water or reflex tachycardia. The antihypertensive effect of perindopril is also observed in patients with low or normal renin concentrations. The effect of perindopril is due to the activity of the metabolite perindoprilate. Other metabolites are not active. Perindopril reduces the load on the heart: - by exerting a vasodilatory effect on the veins, possibly by changing the metabolism of prostaglandins, it reduces the initial load - by reducing the total peripheral vascular resistance it reduces afterload. It has been proven that in patients with heart failure, perindopril: - reduces filling pressure of the left and right ventricle - reduces total peripheral vascular resistance - increases cardiac output and improves cardiac index - increases local blood flow in the muscles. The results of the exercise test are also significantly improved. Indapamide is a sulfonamide derivative with an indole ring, pharmacologically it belongs to the thiazide group of diuretics. Indapamide inhibits sodium reabsorption in the cortical afferent segment. It increases the urinary excretion of sodium and chloride and, to a lesser extent, the excretion of potassium and magnesium, thereby increasing urine output and exerting an antihypertensive effect. Amlodipine is a calcium antagonist that blocks the entry of calcium ions through membranes into the smooth muscle cells of the myocardium and blood vessels. The mechanism of the hypotensive effect of amlodipine is due to a direct relaxing effect on vascular smooth muscle. The exact mechanism of action of amlodipine in angina has not been fully established, but amlodipine reduces ischemia in the following two ways: 1. Dilates peripheral arterioles and thus reduces total peripheral vascular resistance (afterload on the heart). Due to the unloading of the heart, the load on the heart decreases, which leads to a decrease in energy consumption and oxygen demand. 2. Dilates the main coronary arteries and coronary arterioles. Their dilatation increases the supply of oxygen to the myocardium in patients with vasospastic angina (Prinzmetal's angina or variant angina). In patients with arterial hypertension, taking amlodipine in a single daily dose provides a clinically significant reduction in blood pressure over 24 hours in both the supine and standing positions. In patients with angina pectoris, the use of amlodipine once a day increases the time of physical activity, prevents the development of an attack of angina and ST segment depression (by 1 mm). Amlodipine reduces the frequency of angina attacks and the number of short-acting nitroglycerin tablets taken. Amlodipine does not have an adverse effect on metabolism and plasma lipids and can be used in patients with bronchial asthma, diabetes mellitus and gout. Clinical efficacy and safety Perindopril is active in all degrees of hypertension: mild, moderate and severe. A decrease in systolic and diastolic blood pressure is observed in patients both in the “lying” and “standing” positions. Maximum antihypertensive activity after a single dose ranges from 4 to 6 hours and persists for 24 hours. There is a high degree of residual ACF blocking at 24 hours (approximately 80%). In responding patients, normalized blood pressure is achieved after one month and is maintained without tachyphylaxis. Stopping treatment has no reversal effect on hypertension. Perindopril has vasodilatory properties, restores the elasticity of the main arterial trunks, corrects histomorphometric changes in arterial resistance and leads to a decrease in left ventricular hypertrophy. If necessary, the addition of thiazide diuretics gives an additive synergistic effect. The combination of an ACE inhibitor with a thiazide diuretic reduces the risk of hypokalemia associated with taking the diuretic alone. Indapamide in monotherapy has an antihypertensive effect lasting up to 24 hours. This effect occurs in doses in which diuretic properties are minimal. The antihypertensive effect of indapamide is associated with an improvement in arterial elasticity and a decrease in arteriolar resistance and a decrease in total peripheral vascular resistance. Indapamide reduces left ventricular hypertrophy. Thiazide and thiazide-like diuretics, when exceeding the recommended dose, reach a plateau of therapeutic effect, while the frequency of side effects continues to increase. If treatment is not effective enough, increasing the dose is not recommended. It has also been established that indapamide does not affect the metabolism of: - lipids (triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol) - carbohydrates, even in patients with arterial hypertension and diabetes mellitus. Amlodipine Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), which used new therapeutic treatments (amlodipine or ACE inhibitor as first-line therapy) compared with thiazide diuretic for mild to moderate hypertension, did not reveal significant differences in cardiovascular outcomes between amlodipine therapy and thiazide diuretic therapy. The combination of perindopril and indapamide has a dose-dependent antihypertensive effect on diastolic and systolic blood pressure in patients in the supine and standing positions, regardless of age. The effect of the drug lasts for 24 hours. A persistent therapeutic effect develops in less than 1 month from the start of therapy and is not accompanied by tachycardia. Termination of treatment is not accompanied by the development of withdrawal syndrome. It has been proven that the simultaneous administration of perindopril and indapamide has an antihypertensive effect of synergistic origin, which is the result of the individual effects of the drug components. Indications for use: essential hypertension. Method of administration and dosage: For oral administration. The maximum recommended dose of Co-Amlessa is 8 mg/10 mg/2.5 mg per day. One tablet per day as a single dose is preferably taken in the morning, before meals. If necessary, Co-Amlessa tablets with a dosage of 4 mg/10 mg/1.25 mg and 8 mg/10 mg/2.5 mg can be divided into equal doses. The patient can split the 4 mg/10 mg/1.25 mg or 8 mg/10 mg/2.5 mg tablet by placing it on a flat surface with the score facing up and pressing both ends of the tablet with two fingers. Patients with impaired renal function and elderly patients The elimination of perindoprilate is slower in elderly patients, as well as in patients with renal failure. Therefore, routine medical surveillance should include frequent monitoring of creatinine and potassium levels. In patients with severe renal failure (creatinine clearance below 30 ml/min), treatment with Co-Amlessa is contraindicated. Doses of 8 mg/5 mg/2.5 mg and 8 mg/10 mg/2.5 mg are contraindicated in severe to moderate renal failure (creatinine clearance below 60 ml/min). The drug Co-Amlessa can be prescribed to patients with CC ³ 60 ml/min. In these patients, individual dosage titration of the individual components is recommended. Changes in plasma amlodipine concentrations do not correlate with the degree of kidney damage. Patients with liver failure In patients with severe liver failure, treatment with Co-Amlessa is contraindicated. The dosage regimen for patients with moderate hepatic impairment has not been established. Therefore, Co-Amless should be prescribed to such patients with caution. Use in pediatrics The safety and effectiveness of Co-Amlessa in children and adolescents have not yet been established. Side effects The use of perindopril inhibits the renin-angiotensin-aldosterone system and helps reduce potassium loss, which is caused by indapamide. Hypokalemia (potassium level) was observed in 2% of patients taking 2 mg perindopril/0.625 mg indapamide, 4% of patients taking 4 mg perindopril/1.25 mg indapamide, and 6% of patients taking 8 mg perindopril/2.5 mg indapamide. <3.4 mmol/l). The most common adverse reactions during treatment with amlodipine are drowsiness, dizziness, headache, palpitations, flushing, abdominal pain, nausea, ankle swelling, swelling and fatigue. Perindopril/Indapamide Common (≥1/100 to <1/10) - dizziness, headache, paresthesia, vertigo - visual disturbances (including diplopia) - tinnitus - hypotension (and effects associated with hypotension) - shortness of breath , cough - abdominal pain, nausea, epigastric pain, vomiting, dyspepsia, dry mouth, dysgeusia, diarrhea, constipation - anorexia - itching, rash, maculopapular rash - muscle cramps - asthenia Uncommon (≥1/1,000 to <1 /100) - allergic reaction: urticaria - mood changes - sleep disturbances - bronchospasm, - angioedema of the face, limbs, lips, mucous membranes, tongue, glottis and/or larynx - sweating - possible exacerbation of pre-existing acute disseminated lupus erythematosus - disorder renal function - impotence Rarely (from ≥1/10,000 to <1/1,000) - increased levels of bilirubin and liver enzymes in the serum Very rarely (<1/10,000) - leukopenia/neutropenia, agranulocytosis or pancytopenia, thrombocytopenia, aplastic anemia, hemolytic anemia - confusion - angina pectoris, possibly caused by excessive hypotension in high-risk patients - myocardial infarction, possibly caused by excessive hypotension in high-risk patients - arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation) - vasculitis - rhinitis - eosinophilic pneumonia - pancreatitis - hepatitis, cytolytic or cholestatic hepatitis - erythema - Stevens-Johnson syndrome (malignant exudative erythema) - toxic epidermal necrolysis - acute renal failure Unknown (cannot be estimated from the available data) - flutter-flicker (possibly fatal) - possible hepatic encephalopathy in case of liver failure - photosensitivity - hypokalemia - hyponatremia with hypovolemia, causing dehydration and orthostatic hypotension - vasculitis - increased levels of urea in the blood and creatinine in plasma, hyperkalemia Amlodipine Common (from ≥1/100 to <1/10) - drowsiness, dizziness, headache - abdominal pain, nausea - ankle swelling - edema, peripheral edema - fatigue Uncommon (≥1/1,000 to <1/100) - weight gain or loss - insomnia, mood changes - tremor, hypoesthesia, paresthesia - visual impairment (including diplopia) - noise in the ears - a rapid heartbeat - syncope - hypotension (and effects associated with hypotension) - shortness of breath, rhinitis - vomiting, dyspepsia, changes in intestinal motility, dry mouth - alopecia, purple, purple, purple, purple Outcapion of the skin, sweating, itching, rash - arthralgia, myalgia, muscle cramps, back pain - urination disorders, night polyuria, increased urination - impotence, gynecomastia - pain in the chest, asthenia, pain, malaise - reduction or increase in weight rarely ( from ≥1/10,000 DO <1/1,000) - confusion very rarely (<1/10,000) - leukopenia/neutropenia, thrombocytopenia - Quincke's edema, allergic reaction: urticaria - hyperglycemia - hypertension - peripheral neuropathy - myocardial infarction, possibly caused excessive hypotension in patients of high risk groups - arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation) - cough - hypertrophic gingivitis - pancreatitis, gastatitis, cholestatic jaundice - erythema (various species) - angioedaurotic edema of the face, limbs, lips, mucous membranes, mucous membranes of mucous membranes , language, voice gap and/or larynx-erythema-exfoliative dermatitis-Stevens-Johnson syndrome (malignant exudative erythema)-photosensitivity-increasing the level of hepatic enzymes: ACT, ACT (mainly complying with cholestasis) when taking calcium channels blockers were reported about single cases of extrapyramidal syndrome. Contraindications tied with perindopril: - increased sensitivity to the perindopril (or any other AKF inhibitor) - an anhionaurotic edema in an anamnesis associated with the previous treatment of ACF inhibitors - hereditary or idiopathic angiourotic edema - pregnancy tied with indapamide: - increased sensitivity to Indapamide (or any other other sulfonamide derivatives) - renal failure of severe and moderate degree (KC <60 ml min) - severe liver failure - liver encephalopathy - hypokalemia - simultaneous use of antiarrhythmic drugs that can cause ventricular ari - lactation tied with amlodipine: - increased sensitivity amlodipine (or any one other dihydropyridine derivatives) or to any of the auxiliary substances - severe arterial hypotension - shock, including cardiogenic shock - obstruction of the output tract of the left ventricle (for example, severe aortic stenosis) - hemodynamically unstable heart failure after acute myocardial infarction due to the lack of sufficient therapeutic experience of the use of , Ko-Amlyce tablets should not be used in patients:-located on dialysis-with incurable decompensated heart failure (in the absence of the main treatment)-children and adolescence up to 18 years of drug interaction, not recommended combinations with a combined administration of lithium and AKF inhibitors have cases of reversible Increasing the concentration of lithium in serum and cases of toxicity. The simultaneous use of thiazide diuretics can additionally increase lithium levels and enhance the toxic effect of lithium with AKF inhibitors. The use of a combination of perindopamil and indapamide with lithium is not recommended, but if it is necessary to use this combination, careful monitoring of lithium levels in the blood serum, although the content of potassium in serum is usually within the norm, in some patients taking perindopril, hypercalemia may occur. Potassium -saving diuretics (for example, spironolactone, triamteren or amyloride), potassium additives and potassium -containing salt substitutes can lead to a significant increase in potassium in blood serum. Therefore, the combined intraindopril intake with these drugs is not recommended. If the concomitant use of these drugs is indicated due to severe hypokalemia, then when taking them, special care should be observed and frequent monitoring of potassium content in blood serum. Estrustine increases the risk of undesirable effects, such as angioedema (angiootek). Combinations that require special caution of Baclofen enhances the severity of the hypotensive effect. Monitoring of blood pressure and renal function is necessary, and it is also necessary to adapt the dose of the antihypertensive drug. Non -steroidal anti -inflammatory drugs (NSAIDs), including aspirin in high doses while taking them with AKF inhibitors reduce the hypotensive effect. The concomitant reception of AKF and NSAID inhibitors can increase the risk of deterioration of the renal function, including possible acute renal failure, an increase in potassium content in blood serum, especially in patients with an existing impaired renal function. The combined intake of these drugs should be prescribed with caution, especially in elderly patients. Monitoring the adequate hydration of the body of patients should be monitored. At the beginning of combined therapy, as well as periodically during therapy, monitoring of the renal function should be carried out. In patients receiving antidiabetic drugs (insulin, hypoglycemic sulfonamides), the simultaneous use of AKF inhibitors can lead to an increase in their hypoglycemic effect. Hypoglycemia rarely occurs (probably an improvement in glucose tolerance, followed by a decrease in the need for insulin). Due to the risk of hypokalemia, indapamide should be used with caution in combination with drugs that cause trepidation, such as antiarrhythmic drugs of class IA (quinidine, hydrochinidine, dysopiramid); Antiarrhythmic drugs of class III (amiodarone, pre -Pofilid, iboulid, Bretilia, Sotalol); some antipsychotics (chlorpromazine, cyamemazine, leftompromazine, thiooridase, trifluoperazine), benzamides (amisiprides, sulpiride, sultopride, tiapid), butyrophenons (Dropeidol, haloperidol), other neuroleptics (pimoside); Other substances, such as Bepril, Cisapride, Difemanil, Erythromycin IV, Halophantrin, Mizolastin, Moxifloxacin, Pentamidin, Sparfloxacin, Vincamine IV, Methadone, Astemizole, Terphenin. Prevention of potassium levels and dose adjustment is necessary, if necessary, monitoring the QT interval. Drugs that reduce potassium levels, (amphotericin in (B/c), systemic glucocorticoids and mineralocorticoids (systemic use), tetracosactides, stimulating laxatives) increase the risk of potassium levels (additive effect), and therefore careful monitoring of potassium levels and potassium levels are needed and dose adjustment; Particular attention is required in cases of treatment with cardiac glycosides. The use of stimulating laxatives is prohibited by cardiac glycosides: the low level of potassium favors the toxic effects of heart glucosides, and therefore it is necessary to monitor the level of potassium and ECG, and/or, if necessary, reconsider the treatment. Metformin: Lactoacidosis in connection with Metmorphine, caused by a possible functional renal failure, is associated with diuretics, in particular with loop diuretics. It is impossible to use metorphine at the level of creatinine in plasma above 15 mg/l (135 micromol/l) in men and 12 mg/l (110 micromol/l) in women. Iodated contrasting drug: in cases where dehydration is caused by diuretics, there is an increased risk of acute renal failure, especially when using high doses of an iodized contrast drug. Before the introduction of the iodized composition, it is necessary to restore the volume of fluid. Calcium salts increase the level of calcium in connection with reduced removal of calcium in urine. Cyclosporin increases the risk of increasing creatinine without changing the circulating level of cyclosporine, even if there is no decrease in salt or water. The simultaneous use of amlodipine with a strong or moderate CYP3A4 inhibitor (proteases, nesol fungicides, macrolides, like erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in amlodipine exposure. The clinical transition of these changes in the PC can be more pronounced in the elderly. In this regard, clinical monitoring and dose’s selection may be necessary. The simultaneous use of CYP3A4 inducers (for example, rifampicin, St. John's wort of perforated) can lead to a decrease in the plasma concentration of amlodipine. Amlodipine should be used with caution with CYP3A4 inducers. Grapefruit juice in some patients can increase bioavailability and hypotensive effect of amlodipine. Dantrolene (infusion): Given the risk of hyperkalemia, the simultaneous use of calcium channels, such as amlodipine in patients sensitive to malignant hyperthermia and the treatment of malignant hyperthermia, should be avoided. The simultaneous multiple use of amlodipine at a dose of 10 mg with simvastatin at a dose of 80 mg led to an increase in the effects of simvastatin by 77%, compared with monotherapy of simvastatin. It is recommended to limit the dose of simvastatin in patients taking amlodipine to 20 mg per day. Combinations that require caution of imipramine -like (tricyclic) antidepressants, antipsychotics cause increased hypotensive effects, an increase in the risk of development of orthostatic hypotension (additive effect). Corticosteroids, tetracosactide reduce the hypotensive effect (water retention and electrolytes caused by corticosteroids). With the simultaneous use of the drug Ko-Amles with other antihypertensive drugs, a more pronounced decrease in blood pressure occurs. Allopurinol, cytostatic or immunosuppressive drugs, systemic glucocorticosteroids or prokaamine, while using AKF inhibitors, can contribute to the development of leukopenia. AKF inhibitors enhance the antihypertensive effect of certain means for general anesthesia. Combinations that should be taken into account in patients taking diuretics, especially in patients with a reduced volume of circulating blood and/or salt deficiency, after the start of treatment with AKF inhibitor, excessive decrease in blood pressure can be observed. The abolition of the diuretic, an increase in the volume of circulating blood or the use of salt before the start of treatment, as well as the prescription of low initial doses of perindopril and their gradual increase reduce the risk of hypotension. Sympathomy can reduce the hypotensive effect of AKF inhibitors. Rare reports of nitrite reactions (symptoms that include facial redness, nausea, vomiting and hypotension) were received in patients undergoing injection therapy with gold -containing drugs (sodium aurotiomalat) and concomitant treatment with AKF inhibitors, including perindopril. Special instructions in patients taking AKF inhibitors noted neutropenia/ agranulocytosis, thrombocytopenia and anemia. 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-cainamine, or those who have all these complicates

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:

img_f-KK-

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.

Instructions for use of Co-amless (tablets): description, composition, FTG, INN