Instructions Cardipril 2.5 capsules 2.5 mg blister No. 30
Composition
active ingredient: ramipril;
1 capsule contains ramipril 2.5 mg;
excipient: pregelatinized starch.
Dosage form
Capsules.
Main physicochemical properties: hard gelatin capsules, size 4, red-brown/white in color, capsule contents – white or almost white powder.
Pharmacotherapeutic group
Angiotensin-converting enzyme (ACE) inhibitors. Monocomponent ACE inhibitors. Ramipril.
ATX code C09A A05.
Pharmacological properties
Pharmacodynamics
Ramiprilat, the active metabolite of ramipril, inhibits the enzyme dipeptidylcarboxypeptidase I (synonyms: angiotensin-converting enzyme (ACE); kininase II). In blood plasma and tissues, this enzyme catalyzes the conversion of angiotensin I to angiotensin II, an active vasoconstrictor, and also blocks the breakdown of the active vasodilator bradykinin. The reduction in the formation of angiotensin II and the inhibition of the breakdown of bradykinin cause vasodilation. Since angiotensin II also stimulates the release of aldosterone, ramiprilat reduces aldosterone secretion.
ACE inhibitors are effective even in patients with hypertension who have low renin levels. The average response to ACE inhibitor monotherapy in black patients (usually a low-renin hypertensive population) is lower than in non-black patients.
Ramipril administration causes a significant decrease in peripheral arterial resistance. In general, renal plasma flow and glomerular filtration rate do not change significantly.
Administration of ramipril to patients with arterial hypertension leads to a decrease in blood pressure in the supine and standing positions, without a compensatory increase in heart rate.
In most patients, the antihypertensive effect of a single oral dose is apparent within 1-2 hours. The maximum effect of a single dose is usually achieved within 3-6 hours and usually lasts for 24 hours.
The maximum antihypertensive effect of long-term treatment with ramipril is generally observed after 3-4 weeks. It has been shown to persist for 2 years with long-term therapy.
In response to abrupt discontinuation of ramipril, there is no rapid and significant increase in blood pressure.
In patients with severe non-diabetic or diabetic nephropathy, ramipril reduces the rate of progression of renal failure and the onset of end-stage renal failure, and consequently the need for dialysis or kidney transplantation. In patients with the first manifestations of non-diabetic or diabetic nephropathy, ramipril reduces albumin excretion.
Studies have shown that ramipril significantly reduces the incidence of myocardial infarction (by 20%), stroke (by 32%), or cardiovascular mortality (by 26%). In addition, ramipril reduces overall mortality and the need for revascularization, and delays the onset and progression of congestive heart failure. Ramipril reduces the risk of nephropathy in the general population and in patients with diabetes. Ramipril also significantly reduces the incidence of microalbuminuria. These effects were observed in patients with both hypertension and normotensive patients.
Pharmacokinetics
The liver undergoes presystemic metabolism of the prodrug ramipril to form the sole active metabolite ramiprilat (via hydrolysis, which occurs mainly in the liver). In addition to this activation to form ramiprilat, ramipril is glucuronidated to ramipril diketopiperazine (ester). Ramiprilat is also glucuronidated to ramiprilat diketopiperazine (acid).
As a result of this activation/metabolism of the prodrugs, approximately 20% of orally administered ramipril is bioavailable. The bioavailability of ramiprilat after oral administration of 2.5 and 5 mg ramipril is approximately 45%, compared with its availability after intravenous administration of the same doses.
After oral administration of 10 mg of radiolabeled ramipril, approximately 40% of the total label is excreted in the feces and approximately 60% in the urine. After oral administration of 5 mg of ramipril to patients with bile duct drainage, approximately equal amounts of ramipril and its metabolites are excreted in the urine and bile during the first 24 hours.
Approximately 80-90% of the metabolites in urine and bile are ramiprilat or ramiprilat metabolites. Ramipril glucuronide and ramipril diketopiperazine account for approximately 10-20% of the total, and unmetabolized ramipril accounts for approximately 2%.
Animal studies have shown that ramipril is excreted in milk.
Peak plasma concentrations of ramipril are reached 1 hour after oral administration. The elimination half-life of ramipril is approximately 1 hour. Peak plasma concentrations of ramiprilat are observed between 2 and 4 hours after oral administration of ramipril.
The decline in plasma ramiprilat concentrations occurs in several phases. The half-life of the initial distribution and elimination phase is approximately 3 hours. This is followed by a transitional phase (with a half-life of approximately 15 hours) and then a terminal phase during which plasma ramiprilat concentrations are very low, with a half-life of approximately 4-5 days.
The presence of the terminal phase is due to the slow dissociation of ramiprilat from the close but saturated bond with ACE.
Despite the long terminal elimination phase, after a single dose of ramipril at a dose of 2.5 mg and above, steady state – when plasma concentrations of ramiprilat remain constant – is reached after about 4 days. After multiple doses, the “effective” elimination half-life is 13-17 hours, depending on the dose.
In-vitro studies have shown that the inhibition constant of ramiprilat is 7 mmol/L, and the half-life of ramiprilat from ACE is 10.7 hours, indicating its high activity.
The binding of ramipril and ramiprilat to serum proteins is about 73% and 56%, respectively.
In healthy subjects aged 65 to 76 years, the kinetics of ramipril and ramiprilat are similar to those in young healthy subjects.
In patients with impaired renal function, the renal excretion of ramiprilat is reduced, and the renal clearance of ramiprilat is reduced in proportion to creatinine clearance. This results in increased plasma concentrations of ramiprilat, which decrease much more slowly than in patients with normal renal function.
When administered in high doses (10 mg) with impaired liver function, the conversion of ramipril to ramiprilat occurs later, plasma concentrations of ramipril increase and the elimination of ramiprilat slows down.
As in healthy subjects and hypertensive patients, no significant accumulation of ramipril and ramiprilat was observed in patients with congestive heart failure after oral administration of 5 mg ramipril once daily for 2 weeks.
Indication
Treatment of arterial hypertension. Prevention of cardiovascular diseases: reduction of cardiovascular morbidity and mortality in patients with: severe cardiovascular disease of atherothrombotic origin (history of ischemic heart disease or stroke or peripheral vascular disease); diabetes mellitus, who have at least one cardiovascular risk factor. Treatment of kidney disease: initial glomerular diabetic nephropathy, as evidenced by the presence of microalbuminuria; severe glomerular diabetic nephropathy, as evidenced by the presence of macroproteinuria, in patients who have at least one cardiovascular risk factor; severe glomerular non-diabetic nephropathy, as evidenced by the presence of macroproteinuria ≥ 3 g per day. Treatment of heart failure, which is accompanied by clinical manifestations. Secondary prevention after acute myocardial infarction: reduction of mortality during the acute stage of myocardial infarction in patients with clinical signs of heart failure, provided that treatment is started more than 48 hours after the onset of acute myocardial infarction.
Contraindication
The drug is not recommended for use in children (under 18 years of age).
Hypersensitivity to the active substance or to any of the excipients included in the formulation or to other ACE (angiotensin-converting enzyme) inhibitors (see section "Composition"); history of angioedema (hereditary, idiopathic or previously suffered against the background of the use of ACE inhibitors or angiotensin II receptor antagonists); significant renal artery stenosis (bilateral stenosis or stenosis of the artery to a solitary kidney); hypotensive or hemodynamically unstable conditions, systemic lupus erythematosus, scleroderma (increased risk of neutropenia or agranulocytosis); suppression of bone marrow hematopoiesis; hyperkalemia, kidney transplantation, renal failure, hyponatremia (risk of dehydration, hypotension, renal failure), hepatic failure, primary hyperaldosteronism.
Pregnant women or women planning to become pregnant (see section “Use during pregnancy and breastfeeding”).
Should not be used with aliskiren-containing drugs in patients with diabetes mellitus or moderate or severe renal impairment (GFR < 60 mL/min).
The use of ramipril or other ACE inhibitors in combination with extracorporeal therapy methods that may cause blood to come into contact with negatively charged surfaces should be avoided, as there is a risk of severe anaphylactoid reactions, which can sometimes lead to severe anaphylactic shock. Therefore, dialysis or hemofiltration using polyacrylonitrile, sodium-2-methylsulfonate membranes with high ultrafiltration activity (e.g., "AN 69") and LDL (low-density lipoprotein) apheresis using dextran sulfate should not be performed while taking ramipril.
Interaction with other medicinal products and other types of interactions
Contraindicated combinations
Extracorporeal therapy methods that result in contact of blood with negatively charged surfaces, such as dialysis or hemofiltration using certain high flux membranes (e.g. polyacrylonitrile membranes) and LDL apheresis using dextrin sulfate - due to the increased risk of severe anaphylactoid reactions (see section "Contraindications"). If such treatment is necessary, the use of a different dialysis membrane or the use of a different class of antihypertensive agents should be considered.
The combined use of ramipril with aliskiren-containing medicinal products is contraindicated in patients with diabetes mellitus or moderately severe renal impairment and is not recommended for other patient categories (see sections "Contraindications" and "Special warnings and precautions for use").
Combinations requiring precautions
Not recommended combinations
Potassium salts, heparin, potassium-sparing diuretics and other active substances that increase plasma potassium levels (including angiotensin II antagonists, trimethoprim, tacrolimus, ciclosporin): An increase in serum potassium concentration should be expected. During concomitant treatment with ramipril and potassium-sparing diuretics (e.g. spironolactone) or potassium salts, careful monitoring of serum potassium concentration is necessary.
Use with caution.
Antihypertensive drugs (e.g. diuretics) and other drugs that may lower blood pressure (e.g. nitrates, tricyclic antidepressants, anaesthetics, alcohol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin): an increase in the hypotensive effect of ramipril should be expected. Regular monitoring of serum sodium levels is recommended in patients receiving concomitant diuretic treatment (see section 4.4 for diuretics).
Vasopressor sympathomimetics and other substances (e.g. isoproterenol, dobutamine, dopamine, epinephrine). May reduce the blood pressure lowering effect. Particularly careful monitoring of blood pressure is recommended.
Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other drugs that can cause changes in the blood count may increase the likelihood of hematological reactions when used concomitantly with ramipril.
Lithium salts. Excretion of lithium may be reduced by ACE inhibitors. This reduction may lead to increased serum lithium concentrations and increased lithium toxicity. Therefore, lithium concentrations should be carefully monitored.
Antidiabetic agents (e.g., insulin and sulfonylureas)
ACE inhibitors may enhance the effect of insulin. In isolated cases, this may lead to a hypoglycemic reaction in patients taking antidiabetic agents concomitantly. At the beginning of treatment, particularly careful monitoring of blood glucose levels is recommended.
Food
Food does not significantly alter the absorption of ramipril.
Take into account
Non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin and acetylsalicylic acid. The blood pressure-lowering effect of ramipril may be reduced. In addition, concomitant treatment with ACE inhibitors and NSAIDs may increase the risk of worsening of renal function and an increase in serum potassium.
Heparin: Possible increase in serum potassium concentration.
Alcohol: Increased vasodilation. Ramipril may enhance the effects of alcohol.
Salt: Increased salt intake may reduce the antihypertensive effect of Cardipril.
Specific hyposensitization. ACE inhibition increases the likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom. It is believed that this effect may also be observed for other allergens.
Application features
Ramipril should be used under the constant supervision of a physician.
Special categories of patients
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with aliskiren-containing medicinal products.
Dual blockade of the renin-angiotensin-aldosterone system by the combined use of ramipril and aliskiren is not recommended, as there is an increased risk of developing arterial hypotension, hyperkalemia and changes in renal function.
The combined use of ramipril and aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60 ml/min) (see section "Contraindications").
Anaphylactic reactions during desensitization. The use of ACE inhibitors increases the likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom and other allergens. Ramipril should be temporarily discontinued before desensitization.
Cases of intestinal angioedema have been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases, facial angioedema also occurred. The symptoms of intestinal angioedema resolved after discontinuation of the ACE inhibitor.
There is insufficient relevant therapeutic experience in patients with severe renal impairment (creatinine clearance below 20 ml/min per 1.73 m2 body surface area).
Patients with increased activity of the renin-angiotensin system
Special caution should be exercised when treating patients with an overactive renin-angiotensin system. Such patients are at risk of an unexpected and significant decrease in blood pressure and deterioration of renal function as a result of ACE inhibition, especially when an ACE inhibitor or concomitant diuretic is administered for the first time or at a higher dose. Blood pressure should be closely monitored during initiation of therapy or when the dose is increased, as there is a risk of a sudden decrease.
Increased activity of the renin-angiotensin system, which requires medical supervision, including constant monitoring of blood pressure, can be expected, in particular:
in patients with severe, and especially malignant hypertension. Special medical supervision is required in the initial phase of treatment; in patients with heart failure, especially severe or treated with other drugs that can lower blood pressure. In the case of severe heart failure, special medical supervision is required in the initial phase of treatment; in patients with hemodynamically significant difficulties in the inflow or outflow of blood from the left ventricle (e.g. due to aortic stenosis or mitral valve stenosis or hypertrophic cardiomyopathy). Special medical supervision is required in the initial phase of treatment; in patients with hemodynamically significant renal artery stenosis. Close medical supervision is required in the initial phase of treatment. It may be necessary to discontinue the initiated diuretic treatment; in patients who have previously taken diuretics. If discontinuation or reduction of the diuretic dose is not possible, special medical supervision is required in the initial phase of treatment; in patients who are or may become dehydrated (as a result of insufficient fluid or salt intake, or, for example, due to diarrhea, vomiting or excessive sweating, in cases where compensation for fluid and salt loss is insufficient); in patients undergoing major surgery or during anesthesia with drugs that cause arterial hypotension.
In general, correction of dehydration, hypovolemia, or salt depletion is recommended before initiating treatment (however, in patients with heart failure, such corrective measures should be carefully evaluated in terms of the risk of volume overload). In clinically significant conditions, treatment should only be initiated or continued if appropriate measures are taken to prevent excessive hypotension and deterioration of renal function.
Patients with liver disease
In patients with impaired liver function, the response to treatment may be either increased or decreased. In addition, in patients with severe cirrhosis of the liver with edema and/or ascites, the activity of the renin-angiotensin system may be significantly increased; therefore, special caution should be exercised when treating these patients.
Patients with a significant decrease in blood pressure are at particular risk. Patients for whom a significant decrease in blood pressure is a particular risk (e.g. patients with haemodynamically significant stenosis of the coronary arteries or vessels supplying blood to the brain) require special medical supervision during the initial phase of treatment.
Elderly people
Elderly patients may respond more to ACE inhibitors. Assessment of renal function is recommended at the beginning of treatment.
Surgery: If possible, treatment with angiotensin-converting enzyme inhibitors such as ramipril should be discontinued 1 day before surgery.
Monitoring renal function
It is recommended to monitor renal function before and during treatment and adjust the dose, especially in the first weeks of treatment with an ACE inhibitor. Particularly careful monitoring is required in patients with:
heart failure; vasorenal disease, including patients with hemodynamically significant unilateral renal artery stenosis. In the latter group of patients, even a slight increase in serum creatinine may indicate unilateral deterioration of renal function; decreased renal function; transplanted kidney.
Monitoring electrolyte balance
Hyperkalemia: Hyperkalemia has been observed in some patients treated with ACE inhibitors, including ramipril. Patients at risk for hyperkalemia include patients with renal insufficiency, patients over 70 years of age, patients with uncontrolled diabetes mellitus, patients taking potassium salts, potassium-sparing diuretics, or other active substances that increase plasma potassium levels, or patients with conditions such as dehydration, acute cardiac decompensation, or metabolic acidosis. If concomitant use of the above-mentioned drugs is considered appropriate, regular monitoring of plasma potassium levels is recommended (see section 4.5).
Electrolyte monitoring. Hyponatremia. In some patients treated with ramipril, the syndrome of inappropriate antidiuretic hormone secretion with subsequent development of hyponatremia has been observed. It is recommended to regularly monitor serum sodium levels in the elderly and in other patients at risk of developing hyponatremia.
Neutropenia/agranulocytosis. Cases of neutropenia/agranulocytosis, as well as thrombocytopenia and anemia, have been observed rarely. Bone marrow suppression has also been reported. Monitoring of the white blood cell count is recommended to detect possible leukopenia. More frequent monitoring is advisable at the beginning of treatment and in patients with impaired renal function, concomitant collagen disease (e.g. systemic lupus erythematosus or scleroderma) or in those taking other medicinal products that may cause changes in the blood picture (see sections “Interaction with other medicinal products and other forms of interaction” and “Adverse reactions”).
Hematological monitoring
It is recommended to monitor the white blood cell count for early detection of possible leukopenia. More frequent monitoring is recommended during the initial phase of treatment in patients with reduced renal function, with concomitant collagen disease (e.g. lupus erythematosus or scleroderma) or in those treated with other drugs that may cause changes in the blood picture. Cases of neutropenia/agranulocytosis, as well as thrombocytopenia and anemia have been observed rarely. Bone marrow depression has also been reported.
Ethnic differences. ACE inhibitors cause angioedema more frequently in black patients than in non-black patients. As with other ACE inhibitors, the antihypertensive effect of ramipril may be less pronounced in black patients than in non-black patients. This may be because black patients with hypertension tend to have low-renin hypertension.
Cough: Cough has been reported with ACE inhibitors. It is characteristic that the cough is non-productive, persistent and resolves after discontinuation of therapy. The possibility of cough due to ACE inhibitors should be considered in the differential diagnosis of cough.
Ability to influence reaction speed when driving vehicles or other mechanisms
Some side effects (e.g. symptoms of low blood pressure, such as dizziness) may impair the patient's ability to concentrate and reduce the speed of their reactions, which is risky in situations where these qualities are particularly important (e.g. when driving vehicles or operating other machinery).
This is usually possible at the beginning of treatment or when switching from other drugs to treatment with the drug. After taking the first dose or a subsequent increase in dose, it is advisable not to drive or operate other machinery for several hours.
Use during pregnancy or breastfeeding
Pregnancy
The drug is contraindicated for use in pregnant women or women planning to become pregnant. If pregnancy is detected during therapy, the drug should be discontinued immediately and, if necessary, replaced with another drug approved for use in pregnant women (see section "Contraindications").
Breast-feeding
Due to the lack of information regarding the use of ramipril during breastfeeding, this drug is not recommended for use in breastfeeding women and alternative treatments with better established safety profiles during lactation are preferable, especially while breastfeeding a newborn or preterm infant.
Method of administration and doses
Drug for oral use.
It is recommended to take the drug at the same time every day. The drug can be taken before, during, or after meals, as food intake does not affect the bioavailability of the drug. The capsules should be swallowed whole with water. They should not be chewed or crushed.
Adults
It is advisable to discontinue the diuretic 2-3 days before starting treatment with ramipril, if possible (see section "Special warnings and precautions for use").
In patients with arterial hypertension who cannot discontinue the diuretic, treatment with the drug should be initiated at a dose of 1.25 mg (used in an appropriate dosage). Kidney function and blood potassium levels should be carefully monitored. Further dosage of the drug should be adjusted depending on the target blood pressure level.
Arterial hypertension
The dose should be selected individually, depending on the characteristics of the patient's condition (see section "Special instructions for use") and the results of control blood pressure measurements. Ramipril can be used as monotherapy or in combination with other classes of antihypertensive drugs.
Initial dose: Treatment with the drug should be initiated gradually, starting with the recommended initial dose of 2.5 mg per day.
In patients with a strongly activated renin-angiotensin-aldosterone system, a significant decrease in blood pressure may occur after the initial dose. For such patients, the recommended starting dose is 1.25 mg (to be administered in an appropriate dosage regimen) and their treatment should be initiated under medical supervision (see section 4.4).
Dose titration and maintenance dose. The dose may be doubled every 2-4 weeks until the target blood pressure is reached; the maximum dose of ramipril is 10 mg per day. The drug should usually be taken once daily.
(Also see above regarding dosing information for patients receiving diuretics.)
Prevention of cardiovascular diseases
Starting dose: The recommended starting dose of ramipril is 2.5 mg once daily.
Dose titration and maintenance dose. Depending on individual tolerability, the dose should be increased gradually. It is recommended to double the dose after 1-2 weeks of treatment, and then - after another 2-3 weeks - increase it to the target maintenance dose of 10 mg 1 time per day.
(Also see above regarding dosing information for patients receiving diuretics.)
Kidney disease treatment
For patients with diabetes and microalbuminuria.
Initial dose. The recommended initial dose of the drug is 1.25 mg once a day (to be used in the appropriate dosage).
Dose titration and maintenance dose. Depending on individual tolerability of the drug, the dose should be increased during further treatment. After 2 weeks of treatment, it is recommended to double the single daily dose to 2.5 mg, and then to 5 mg after another 2 weeks of treatment.
(Also see above regarding dosing information for patients receiving diuretics.)
In patients with diabetes and at least one cardiovascular risk factor.
Starting dose: The recommended starting dose of ramipril is 2.5 mg once daily.
Dose titration and maintenance dose. Depending on individual tolerability of the drug, the dose should be increased during further treatment. After 1-2 weeks of treatment, it is recommended to double the daily dose of the drug to 5 mg, and then to 10 mg after another 2-3 weeks of treatment. The target daily dose is 10 mg.
(Also see above regarding dosing information for patients receiving diuretics.)
For patients with non-diabetic nephropathy, as evidenced by macroproteinuria ≥ 3 g/day.
Initial dose: The recommended initial dose of ramipril is 1.25 mg once daily (to be administered in the appropriate dosage).
Dose titration and maintenance dose. Depending on the individual patient's tolerance of the drug, the dose should be increased during further treatment. After 2 weeks of treatment, it is recommended to double the single daily dose to 2.5 mg, and then to 5 mg after another 2 weeks of treatment.
Heart failure with clinical manifestations
Initial dose: For patients whose condition has stabilized after treatment with diuretics, the recommended initial dose of the drug is 1.25 mg per day (to be used in the appropriate dosage).
Dose titration and maintenance dose: The dose of ramipril should be titrated by doubling it every 1-2 weeks until a maximum daily dose of 10 mg is reached. It is advisable to divide the dose into 2 doses.
(Also see above regarding dosing information for patients receiving diuretics.)
Secondary prevention after acute myocardial infarction in the presence of heart failure.
Initial dose. 48 hours after the onset of myocardial infarction, patients who are clinically and hemodynamically stable should be given an initial dose of 2.5 mg twice daily for 3 days. If the initial dose of 2.5 mg is poorly tolerated, then 1.25 mg (used in the appropriate dosage) twice daily for 2 days should be used, followed by an increase to 2.5 mg and 5 mg twice daily. If the dose cannot be increased to 2.5 mg twice daily, treatment should be discontinued.
(Also see above regarding dosing information for patients receiving diuretics.)
Dose titration and maintenance dose. The daily dose should then be increased by doubling it at intervals of 1-3 days until the target maintenance dose of 5 mg twice daily is reached.
If the dose cannot be increased to 2.5 mg twice daily, treatment should be discontinued. There is still insufficient experience in the treatment of patients with severe (NYHA class IV) heart failure immediately after myocardial infarction. If a decision is nevertheless made to treat such patients with this drug, it is recommended to start therapy with a dose of 1.25 mg (used in the appropriate dosage) once daily and any increase should be carried out with extreme caution.
Special categories of patients
Patients with renal impairment. The daily dose for patients with renal impairment depends on the creatinine clearance:
if creatinine clearance is ≥ 60 ml/min, there is no need to adjust the initial dose (2.5 mg per day), and the maximum daily dose is 10 mg; if creatinine clearance is 30-60 ml/min, there is no need to adjust the initial dose (2.5 mg per day), and the maximum daily dose is 5 mg; if creatinine clearance is 10-30 ml/min, the initial daily dose is 1.25 mg per day (use in the appropriate dosage), and the maximum daily dose is 5 mg; patients with arterial hypertension on hemodialysis: ramipril is excreted to a small extent during hemodialysis; the initial dose is 1.25 mg (use in the appropriate dosage), and the maximum daily dose is 5 mg; the drug should be taken a few hours after the hemodialysis session.
Patients with impaired hepatic function: Treatment with ramipril in patients with impaired hepatic function should be initiated under close medical supervision, and the maximum daily dose in such cases should be 2.5 mg.
Elderly patients. The initial dose should be lower and subsequent dose titration should be more gradual because of the higher likelihood of adverse effects, especially in very elderly and debilitated patients. In such cases, a lower initial dose of 1.25 mg ramipril should be prescribed (use in an appropriate dosage).
Children
The drug is not recommended for use in children (under 18 years of age) as there is insufficient data on the efficacy and safety of this drug in such patients.
Overdose
Symptoms: Overdose may cause excessive peripheral vasodilation (with severe hypotension, shock), bradycardia, electrolyte imbalance and renal failure.
Treatment. The patient should be carefully monitored and symptomatic and supportive therapy should be administered. The proposed treatment measures include primary detoxification (gastric lavage, administration of adsorbents), as well as measures aimed at restoring stable hemodynamics, including the administration of alpha-1-adrenoceptor agonists or angiotensin II (angiotensinamide). Ramiprilat, the active metabolite of ramipril, is poorly removed from the systemic circulation by hemodialysis.
Adverse reactions
Because ramipril is an antihypertensive agent, many of its adverse effects are secondary to its ability to lower blood pressure, resulting in adrenergic feedback or organ hypoperfusion. Numerous other effects (e.g., effects on electrolyte balance, certain anaphylactoid reactions, or mucosal inflammatory reactions) are due to ACE inhibition or other pharmacological effects of this class of drugs. Serious adverse reactions include angioedema, persistent cough, hyperventilation, and
