Ko-Dalneva, 30 pcs., 5 mg+0.625 mg+2 mg, tablets
Amlodipine
Concomitant use is not recommended
Dantrolene (intravenous administration).
In laboratory animals, cases of ventricular fibrillation with death and collapse have been reported during the use of verapamil and intravenous administration of dantrolene, accompanied by hyperkalemia. Due to the risk of hyperkalemia, it is recommended to avoid the simultaneous use of a CCB (amlodipine) and dantrolene in patients susceptible to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.
Concomitant use requiring special attention
Inducers of the CYP3A4 isoenzyme.
There are no data regarding the effect of inducers of the CYP3A4 isoenzyme on amlodipine. The simultaneous use of inducers of the CYP3A4 isoenzyme (rifampicin, St. John's wort preparations) may lead to a decrease in the concentration of amlodipine in the blood plasma. Caution should be exercised when taking amlodipine simultaneously with inducers of the CYP3A4 isoenzyme.
Inhibitors of the CYP3A4 isoenzyme.
Concomitant use of amlodipine with strong or moderate inhibitors of the CYP3A4 isoenzyme (protease inhibitors, azole antifungals, macrolides, such as erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. Clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients, and therefore monitoring of the clinical condition and dose adjustment may be required.
Concomitant use requiring attention
Amlodipine enhances the antihypertensive effect of drugs for antihypertensive therapy.
Other drug combinations.
In clinical drug interaction studies, amlodipine had no effect on the pharmacokinetics of atorvastatin, digoxin, warfarin or cyclosporine. Concomitant use of amlodipine and consumption of grapefruits or grapefruit juice is not recommended due to the possible increase in the bioavailability of amlodipine in some patients, which may lead to an enhanced antihypertensive effect.
Indapamide
Concomitant use requiring special attention
Drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type.
Given the risk of developing hypokalemia, caution should be exercised when using indapamide simultaneously with drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type, for example, antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, bretylium tosylate, sotalol), some antipsychotics ( chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other antipsychotics (pimozide), other drugs such as bepridil, cisapride, difemanil methyl sulfate, erythromycin IV c, halofantrine, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine IV, methadone, astemizole, terfenadine. Simultaneous use with the above drugs should be avoided; if hypokalemia develops, correct it and monitor the ECG (QT interval).
Drugs that can cause hypokalemia.
Concomitant use with intravenous amphotericin B, systemic corticosteroids and mineralocorticosteroids, tetracosactide, laxatives that stimulate gastrointestinal motility increases the risk of hypokalemia (additive effect). It is necessary to monitor the potassium content in the blood plasma and, if necessary, correct hypokalemia. Particular caution should be observed when used simultaneously with cardiac glycosides. Laxatives that do not stimulate gastrointestinal motility should be used.
Cardiac glycosides.
Hypokalemia enhances the toxic effect of cardiac glycosides. With simultaneous use, you should monitor the potassium content in the blood plasma and ECG indicators and, if necessary, decide on the advisability of continuing therapy.
Concomitant use requiring attention
Metformin.
Functional renal failure, which can occur while taking diuretics, especially loop diuretics, with simultaneous use of metformin increases the risk of developing lactic acidosis. Metformin should not be used if plasma creatinine Cl exceeds 15 mg/l (135 µmol/l) in men and 12 mg/l (110 µmol/l) in women.
Iodinated contrast agents.
Dehydration while taking diuretics increases the risk of developing acute renal failure, especially when high doses of iodinated contrast agents are administered. Before using iodinated contrast agents, it is necessary to compensate for hypovolemia.
Calcium salts.
With simultaneous use, the development of hypercalcemia may occur due to a decrease in calcium excretion by the kidneys.
Cyclosporine.
It is possible to increase Cl creatinine in blood plasma without changing the concentration of cyclosporine, even with normal water and sodium content.
Perindopril
Concomitant use is not recommended
Aliskiren.
Concomitant use of perindopril with aliskiren is contraindicated in patients with diabetes or moderate to severe renal impairment (creatinine clearance less than 60 ml/min).
Potassium-sparing diuretics, potassium supplements and potassium-containing table salt substitutes.
During therapy with ACE inhibitors, the potassium content in the blood plasma, as a rule, remains within normal limits, but hyperkalemia may develop. Concomitant use of potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium supplements and potassium-containing table salt substitutes can lead to a significant increase in potassium levels in the blood plasma. If it is necessary to take an ACE inhibitor simultaneously with the above drugs (in case of hypokalemia), caution should be exercised and regular monitoring of potassium levels in the blood plasma and ECG parameters should be carried out.
Estramustine.
The simultaneous use of ACE inhibitors with estramustine is accompanied by a risk of developing angioedema.
Concomitant use requiring special attention
Double blockade of the RAAS in patients with atherosclerosis, CHF or diabetes mellitus accompanied by target organ damage is associated with a higher incidence of arterial hypotension, fainting, hyperkalemia and renal dysfunction (including the development of acute renal failure) compared with the use of the drug one of the listed groups. Double blockade of the RAAS is possible only in selected cases under careful monitoring of renal function.
NSAIDs, including high doses of acetylsalicylic acid (ASA) (more than 3 g/day).
The simultaneous use of ACE inhibitors with NSAIDs (including ASA at a dose that has an anti-inflammatory effect, COX-2 inhibitors and non-selective NSAIDs) can lead to a decrease in the antihypertensive effect, as well as to a deterioration in renal function, including the development of acute renal failure, and an increase in plasma potassium levels blood, especially in patients with reduced renal function. Caution should be exercised when using this combination, especially in elderly patients. Patients need to compensate for fluid loss and regularly monitor kidney function, both at the beginning of treatment and during treatment.
Hypoglycemic agents (sulfonylureas and insulin)
ACE inhibitors may enhance the hypoglycemic effect of insulin and sulfonylureas in patients with diabetes mellitus. The development of hypoglycemia is very rare (probably due to increased glucose tolerance and decreased insulin requirements).
Concomitant use requiring attention
Diuretics (thiazide and loop).
In patients receiving diuretics, especially those with excessive fluid and/or electrolyte excretion, a significant decrease in blood pressure may be observed when initiating ACE inhibitor therapy. The risk of developing arterial hypotension can be reduced by discontinuing the diuretic, correcting hypovolemia and electrolyte balance, as well as prescribing perindopril in a low dose (2 mg/day), gradually increasing it.
Allopurinol, cytostatic and immunosuppressive drugs, GCS (for systemic use) and procainamide.
Concomitant use with ACE inhibitors may increase the risk of developing leukopenia.
Preparations for general anesthesia.
The simultaneous use of ACE inhibitors and general anesthesia may lead to increased antihypertensive effect.
Gold preparations.
When using ACE inhibitors, incl. perindopril, in patients receiving intravenous gold (sodium aurothiomalate), a symptom complex was described, including facial flushing, nausea, vomiting, and arterial hypotension.
Sympathomimetics.
May weaken the antihypertensive effect of ACE inhibitors.
Gliptins (linagliptin, saxagliptin, sitagliptin, vitagliptin).
Concomitant use with ACE inhibitors may increase the risk of developing angioedema due to the inhibition of dipeptidyl peptidase IV (DPP-IV) activity by gliptin.
Ko-Dalneva®
Concomitant use is not recommended
Lithium preparations.
With the simultaneous use of ACE inhibitors with lithium preparations, a reversible increase in the concentration of lithium in the blood plasma may occur with the development of intoxication. Concomitant use with thiazide diuretics may further increase lithium concentrations and increase the risk of intoxication. The simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended. In the case of this therapy, regular monitoring of the concentration of lithium in the blood plasma is necessary.
Concomitant use requiring special attention
Baclofen.
The antihypertensive effect may be enhanced. Blood pressure and renal function should be monitored and, if necessary, the dose of antihypertensive drugs should be adjusted.
Concomitant use requiring attention
Antihypertensives (eg beta-blockers) and vasodilators.
When used simultaneously with antihypertensive drugs, the antihypertensive effect may be enhanced. Caution should be exercised when used concomitantly with nitroglycerin, other nitrates or other vasodilators, since an additional decrease in blood pressure may occur.
Corticosteroids (mineral and glucocorticosteroids), tetracosactide.
Decreased antihypertensive effect (fluid and sodium retention as a result of the action of corticosteroids).
Alpha blockers (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin).
Strengthening the antihypertensive effect and increasing the risk of developing orthostatic hypotension.
Amifostine.
The antihypertensive effect of amlodipine may be enhanced.
Tricyclic antidepressants/neuroleptics/general anesthesia.
Strengthening the antihypertensive effect and increasing the risk of developing orthostatic hypotension (additive effect).
Dalneva
Special instructions related to amlodipine and perindopril also apply to Dalneva.
Perindopril
Hypersensitivity/angioedema (Quincke's edema)
When using ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, lips, tongue, vocal folds, and/or larynx may occur. If these symptoms appear, use of the drug should be stopped immediately, and the patient should be observed until signs of edema disappear completely.
If angioedema affects only the face and lips, its symptoms usually resolve on their own, or antihistamines can be used to treat the symptoms. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.
If such symptoms appear, you should immediately administer epinephrine (adrenaline) subcutaneously at a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure airway patency. The patient should be under medical supervision until symptoms disappear completely and permanently.
Patients with a history of angioedema not associated with the use of ACE inhibitors may have an increased risk of developing it when using drugs in this group.
In rare cases, intestinal angioedema (angioedema of the intestine) develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal C-1-esterase levels. The diagnosis is made using computed tomography of the abdominal cavity, ultrasound, or at the time of surgery. Symptoms disappear after stopping the use of ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the possibility of developing intestinal angioedema must be taken into account when making a differential diagnosis.
Anaphylactoid reactions during desensitization procedures
There are isolated reports of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitization therapy with Hymenoptera venom. ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, the development of anaphylactoid reactions can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the start of the desensitization procedure.
Anaphylactoid reactions during LDL apheresis using dextran sulfate
In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flux membranes.
Hemodialysis
Anaphylactic reactions have been observed in patients receiving ACE inhibitors during hemodialysis using high-flow membranes. Therefore, it is advisable to use a different type of membrane or use an antihypertensive drug of a different pharmacotherapeutic group.
Neutropenia/agranulocytosis, thrombocytopenia and anemia
In patients taking ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia and anemia may develop. In patients with normal renal function in the absence of other complications, neutropenia rarely develops and resolves spontaneously after discontinuation of ACE inhibitors.
Perindopril should be used with great caution in patients with connective tissue diseases and simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially with existing renal impairment. Some patients may develop severe infections that do not respond to intensive antibiotic therapy. If perindopril is prescribed, monitoring the number of leukocytes in the blood plasma is recommended. The patient should be warned that if any signs of an infectious disease appear (sore throat, fever), consult a doctor immediately.
Risk of arterial hypotension and/or renal failure (in patients with chronic heart failure, fluid and electrolyte imbalance, etc.)
In liver cirrhosis, accompanied by edema and ascites, arterial hypotension, and CHF, significant activation of the renin-angiotensin-aldosterone system (RAAS) may be observed, especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (against the background of a diet with limited salt or long-term use of diuretics ).
The use of an ACE inhibitor causes blockade of the RAAS, and therefore a sharp decrease in blood pressure and/or an increase in the concentration of creatinine in the blood plasma is possible, indicating the development of acute renal failure, which is more often observed when taking the first dose or during the first two weeks of therapy.
ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely occurs in patients without underlying medical conditions. The risk of an excessive decrease in blood pressure is increased in patients with reduced blood volume, which can be observed during diuretic therapy, while following a strict diet with limited salt, hemodialysis, with diarrhea or vomiting, or in patients with severe arterial hypertension with high renin activity. In patients at high risk of developing symptomatic hypotension, blood pressure, renal function, and serum potassium levels should be carefully monitored during drug therapy.
The same precautions apply to patients with angina pectoris or cerebrovascular diseases, in whom a pronounced decrease in blood pressure can lead to the development of myocardial infarction or cerebrovascular accident.
If arterial hypotension develops, the patient should be transferred to the supine position with legs elevated. If necessary, replenish the blood volume with intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication for further use of the drug. After restoration of blood volume and blood pressure, therapy can be continued.
Aortic stenosis/Mitral stenosis/Hypertrophic obstructive cardiomyopathy
ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as in patients with mitral stenosis.
Potassium-sparing diuretics and potassium supplements
The simultaneous use of perindopril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing salt substitutes is not recommended.
Cough
During therapy with an ACE inhibitor, a dry, nonproductive cough may occur, which disappears after discontinuation of drugs in this group. If a dry cough appears, you should be aware of the possible connection of this symptom with the use of an ACE inhibitor.
Children and adolescents under 18 years of age
The drug is contraindicated in children and adolescents under 18 years of age due to the lack of data on the effectiveness and safety of the drug in this age group.
Renal dysfunction
If renal function is impaired (creatinine clearance less than 60 ml/min), individual selection of doses of perindopril and amlodipine is recommended. Regular monitoring of potassium and creatinine levels in the blood plasma is a necessary condition in the treatment of such patients.
In some patients with bilateral renal artery stenosis or stenosis of the artery of a solitary kidney, taking ACE inhibitors, there was an increase in plasma urea and creatinine concentrations, reversible after discontinuation of therapy. These changes are more likely in patients with renal failure. Patients with renovascular hypertension are at increased risk of severe hypotension and renal failure. In some hypertensive patients without obvious evidence of existing renal disease who took perindopril concomitantly with a diuretic, small and transient increases in serum urea and creatinine concentrations were observed. These changes more often develop in patients with pre-existing renal impairment.
Liver dysfunction
Rarely, the use of ACE inhibitors is accompanied by a syndrome, the development of which begins with cholestatic jaundice and which then progresses to fulminant liver necrosis, sometimes with death. The mechanism of development of this syndrome is unclear. If jaundice occurs or liver transaminases increase during use of an ACE inhibitor, the ACE inhibitor should be discontinued immediately and the patient should remain under appropriate medical supervision.
Ethnic characteristics
In patients of the Negroid race, angioedema develops more often than in representatives of other races while using ACE inhibitors. Perindopril, like other ACE inhibitors, may have a less pronounced hypotensive effect in patients of the Black race compared to representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the Negroid race more often have low plasma renin activity.
Surgery/general anesthesia
The use of ACE inhibitors in patients undergoing major surgery and/or general anesthesia can lead to a significant decrease in blood pressure if general anesthesia agents with a hypotensive effect are used. This is due to blocking the formation of angiotensin II against the background of a compensatory increase in renin activity. If the development of arterial hypotension is associated with the described mechanism, the blood volume should be increased. It is recommended to stop using the drug 24 hours before surgery.
Hyperkalemia
During therapy with ACE inhibitors, including perindopril, plasma potassium levels may increase in some patients. Risk factors for the development of hyperkalemia are renal failure, decreased renal function, old age (over 70 years), diabetes mellitus, intercurrent conditions, in particular dehydration, acute cardiac decompensation, metabolic acidosis, simultaneous use of potassium-sparing diuretics (for example, spironolactone, eplerenone, triamterene or amiloride), potassium-containing drugs or supplements, potassium-containing salt substitutes, or concomitant use of other drugs that increase plasma potassium levels (eg, heparin). Hyperkalemia can cause serious, sometimes life-threatening arrhythmias. If it is necessary to use perindopril and one of the above substances simultaneously, caution should be exercised and the potassium level in the blood plasma should be regularly monitored.
Patients with diabetes mellitus
In patients with diabetes mellitus taking oral hypoglycemic agents and/or insulin, increased monitoring of blood glucose concentrations is necessary during the first few months of therapy with ACE inhibitors.
Amlodipine
Liver dysfunction
In patients with impaired liver function, T1/2 of amlodipine is prolonged. When prescribing the drug to such patients, caution should be exercised and the activity of liver enzymes should be regularly monitored.
Patients with heart failure
In patients with CHF (functional class III and IV according to the NYHA classification), treatment is carried out with caution, due to the possibility of developing pulmonary edema.
