Instructions for Ramipril-Teva tablets 10 mg blister No. 30
Composition
active ingredient: ramipril;
1 tablet contains ramipril 2.5 mg or 5 mg or 10 mg;
excipients: lactose monohydrate, pregelatinized starch, croscarmellose sodium, sodium bicarbonate, sodium stearyl fumarate; 2.5 mg tablets - iron oxide yellow (E 172); 5 mg tablets - iron oxide red (E 172), iron oxide yellow (E 172).
Dosage form
Pills.
Main physicochemical properties:
2.5 mg tablets: yellow, oblong, biplane tablets with two break lines on the sides; upper punch: parallel break line, embossed R/2 and bevel; lower punch: bevel; 10.0 mm × 5.0 mm;
5 mg tablets: pink, oblong, biplane tablets with two break lines on the sides; upper punch: parallel break line, embossed R/3, with bevel; lower punch: with bevel; 8.8 mm × 4.4 mm;
10 mg tablets: white or almost white, oblong, biplane tablets with two break lines on the sides; upper punch: parallel break line, R/4 embossed and bevelled edge; lower punch: bevelled edge; 11.0 mm × 5.5 mm.
Pharmacotherapeutic group
Angiotensin-converting enzyme (ACE) inhibitors. Monocomponent ACE inhibitors. Ramipril. ATC code C09A A05.
Pharmacological properties
Mechanism of action. Ramiprilat, the active metabolite of the prodrug ramipril, is an inhibitor of the enzyme dipeptidylcarboxypeptidase I (synonyms: ACE, kinase II). In plasma and tissues, this enzyme catalyzes the conversion of angiotensin I to angiotensin II (the active vasoconstrictor) and the cleavage of the active vasodilator bradykinin. The reduction in the formation of angiotensin II and the inhibition of the cleavage of bradykinin lead to vasodilation. Since angiotensin II also stimulates the release of aldosterone, ramiprilat causes a decrease in aldosterone secretion. The response to monotherapy with ACE inhibitors was on average less pronounced in black (Afro-Caribbean) hypertensive patients (a population characterized by low-renin states in hypertension) than in patients of other races.
Pharmacodynamics.
Antihypertensive properties. Administration of ramipril causes a significant decrease in peripheral arterial resistance. As a rule, there are no significant changes in renal plasma flow or glomerular filtration rate. Administration of ramipril to patients with arterial hypertension leads to a decrease in blood pressure in both the horizontal and vertical positions of the patient, which is not accompanied by a compensatory increase in heart rate.
After oral administration of a single dose of the drug, the antihypertensive effect occurs in most patients within 1–2 hours, the maximum effect usually occurs after 3–6 hours, and the antihypertensive effect usually persists for 24 hours.
With long-term treatment with ramipril, the maximum antihypertensive effect develops after 3–4 weeks. It has been proven that with long-term therapy, the antihypertensive effect persists for 2 years. Abrupt discontinuation of ramipril does not cause a rapid and excessive increase in blood pressure (rebound phenomenon).
Heart failure. Ramipril has been shown to be effective in patients with heart failure in NYHA functional classes II–IV when used as an adjunct to conventional diuretic therapy and, if necessary, cardiac glycosides. The drug has a beneficial effect on cardiac hemodynamics (reduction of left and right ventricular filling pressures, total peripheral vascular resistance, increase in cardiac output and improvement in cardiac index). It also reduces neuroendocrine activation.
Pharmacokinetics.
Absorption. After oral administration, ramipril is rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 1 hour. Based on the amount of substance recovered in the urine, the extent of absorption is at least 56% and is not significantly affected by the presence of food in the gastrointestinal tract. The bioavailability of the active metabolite ramiprilat after oral administration of ramipril at a dose of 2.5 mg and 5 mg is 45%.
Peak plasma concentrations of ramiprilat, the only active metabolite of ramipril, are reached 2-4 hours after administration of ramipril. After administration of usual doses of ramipril once daily, steady-state plasma concentrations of ramiprilat are reached by approximately the 4th day of treatment.
Distribution: The plasma protein binding of ramipril is approximately 73% and that of ramiprilat is approximately 56%.
Metabolism: Ramipril is almost completely metabolized to ramiprilat, diketopiperazine ester, diketopiperazine acid, and the glucuronides of ramipril and ramiprilat.
After repeated doses of ramipril once daily, the effective half-life is 13–17 hours for doses of 5–10 mg and longer for lower doses (1.25–2.5 mg). The difference is due to the saturable capacity of the enzyme to bind ramiprilat.
Patients with renal impairment (see section 4.2). In patients with renal impairment, renal excretion of ramiprilat is reduced and renal clearance of ramiprilat is proportional to creatinine clearance. This results in increased plasma concentrations of ramiprilat, which decrease more slowly than in subjects with normal renal function.
Patients with impaired hepatic function (see section 4.2). In patients with impaired hepatic function, the metabolism of ramipril to ramiprilat was slowed down due to a decrease in the activity of hepatic esterases, and the plasma levels of ramipril were increased in these patients. However, the maximum concentrations of ramiprilat in these patients did not differ from those in subjects with normal hepatic function.
Breastfeeding: Neither ramipril nor its metabolite were detected in breast milk after a single oral dose. However, the effect of multiple doses is unknown.
Paediatric population. The pharmacokinetic profile of ramipril was studied in 30 hypertensive children aged 2–16 years, weighing >10 kg. After doses of 0.05 to 0.2 mg/kg, ramipril was rapidly and extensively metabolised to ramiprilat. Peak plasma concentrations of ramiprilat were reached after 2–3 hours. Ramiprilat clearance was significantly correlated with logarithm of body weight (p < 0.01) and dose (p < 0.001). Clearance and volume of distribution increased in direct proportion to age in each dose group. Exposure levels were comparable in children at a dose of 0.05 mg/kg to those in adults at a dose of 5 mg ramipril. A dose of 0.2 mg/kg in children resulted in exposure levels that were higher than the maximum recommended dose of 10 mg/day in adults.
Indication
Treatment of arterial hypertension.
Prevention of cardiovascular disease: 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, who have at least one cardiovascular risk factor (see section “Pharmacological properties”).
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 (see section "Pharmacological properties");
– severe glomerular non-diabetic nephropathy, as evidenced by the presence of macroproteinuria ≥ 3 g/day (see section “Pharmacological properties”).
Treatment of symptomatic heart failure.
Secondary prevention after acute myocardial infarction: reduction of mortality during the acute phase 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
Hypersensitivity to the active substance or to any of the excipients included in the medicinal product, or to other ACE inhibitors.
History of angioedema (hereditary, idiopathic or previously experienced while taking ACE inhibitors or angiotensin II receptor antagonists).
Significant bilateral renal artery stenosis or renal artery stenosis in the presence of a single functioning kidney.
Pregnancy and planning pregnancy (see section "Use during pregnancy or breastfeeding").
Arterial hypotension or hemodynamically unstable conditions.
The simultaneous use of Ramipril-Teva with drugs containing aliskiren is contraindicated in patients with diabetes mellitus or renal dysfunction (GFR less than 60 ml/min/1.73 m2) (see sections “Pharmacodynamics” and “Interaction with other medicinal products and other types of interactions”).
Concomitant use with sacubitril/valsartan: Treatment with Ramipril should only be initiated 36 hours after the last dose of sacubitril/valsartan (see sections 4.4 and 4.5).
The concomitant use of ACE inhibitors and extracorporeal therapies that result in contact of blood with negatively charged surfaces should be avoided (see section 4.5).
Interaction with other medicinal products and other types of interactions
Extracorporeal therapies 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 low density lipoprotein apheresis using dextran sulfate, are contraindicated due to the increased risk of severe anaphylactoid reactions (see section 4.3). If such treatment is necessary, consideration should be given to using a different dialysis membrane or a different class of antihypertensive agent.
Medicinal products that increase the risk of angioedema. Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated due to an increased risk of angioedema (see sections 4.3 and 4.4). Ramipril treatment should only be initiated 36 hours after the last dose of sacubitril/valsartan. Sacubitril/valsartan treatment should only be initiated 36 hours after the last dose of ramipril.
Concomitant use of ACE inhibitors with racecadotril, mammalian target of rapamycin (mTOR) inhibitors (e.g. sirolimus, everolimus, temsirolimus) or vildagliptin may lead to an increased risk of angioedema (see section 4.4).
Combinations requiring precautions.
Potassium-sparing diuretics, potassium-containing food supplements or salt substitutes containing potassium. Although serum potassium levels usually remain within normal limits, hyperkalaemia may occur in some patients taking this medicine. Potassium-sparing diuretics (such as spironolactone, triamterene or amiloride), food supplements containing potassium or salt substitutes containing potassium may lead to significant increases in serum potassium. Caution should also be exercised when Ramipril-Teva is used concomitantly with other medicinal products that increase serum potassium levels, such as trimethoprim and co-trimoxazole (trimethoprim/sulfamethoxazole), as trimethoprim is known to act as a potassium-sparing diuretic, as is amiloride. Therefore, the combination of Ramipril-Teva with the above-mentioned medicinal products is not recommended. If concomitant use of such drugs is indicated, treatment should be carried out with caution and serum potassium levels should be monitored frequently (see section "Special warnings and precautions for use").
Cyclosporine: Concomitant use of ACE inhibitors with cyclosporine may cause hyperkalemia. Monitoring of serum potassium is recommended.
Heparin: Concomitant use of ACE inhibitors with heparin may lead to hyperkalemia. Monitoring of serum potassium is recommended.
Tacrolimus: Hyperkalemia may occur, therefore plasma potassium levels should be carefully monitored.
Antihypertensive drugs (e.g. diuretics) and other substances that may lower blood pressure (e.g. nitrates, tricyclic antidepressants, anaesthetics, alcohol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin). An increased risk of arterial hypotension should be expected (see section "Method of administration and dosage" for diuretics).
Vasopressor sympathomimetics and other substances (e.g. isoproterenol, dobutamine, dopamine, epinephrine) which may reduce the antihypertensive effect of Ramipril-Teva. Close monitoring of blood pressure is recommended.
Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that may cause changes in the blood picture. Increased likelihood of hematological reactions (see section "Special instructions").
Lithium salts: ACE inhibitors may reduce lithium excretion, which may lead to increased lithium toxicity. Lithium levels should be carefully monitored.
Antidiabetic agents, including insulin. Hypoglycemic reactions may occur. Close monitoring of blood glucose levels is recommended.
Non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid. The antihypertensive effect of Ramipril-Teva is expected to be reduced. Also, the simultaneous use of ACE inhibitors and NSAIDs may be accompanied by an increased risk of worsening of renal function and an increase in blood potassium levels.
Dual blockade of the renin-angiotensin-aldosterone system: Clinical trial data have shown that dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is associated with an increased incidence of adverse events such as hypotension, hyperkalaemia and worsening renal function (including acute renal failure) compared with the use of a single agent affecting the RAAS (see sections 5.1, 5.3 and 4.4).
Application features
Pregnancy: Treatment with ACE inhibitors (such as ramipril) or angiotensin II receptor antagonists should not be initiated during pregnancy. ACE inhibitors or angiotensin II receptor antagonists should be used during pregnancy only if clearly needed. Patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors/angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative treatment should be started (see sections 4.3 and 4.8).
Patients at particular risk of hypotension.
• Patients with significantly increased RAAS activity
In patients with significantly increased RAAS activity, there is a risk of a sudden significant decrease in blood pressure and deterioration of renal function due to ACE inhibition, especially if an ACE inhibitor or concomitant diuretic is prescribed for the first time or the dose is increased for the first time.
A significant increase in RAAS activity, which requires medical supervision, including constant monitoring of blood pressure, can be expected, for example, in patients:
– with severe arterial hypertension;
– with decompensated congestive heart failure;
– with hemodynamically significant obstruction to the inflow or outflow of blood from the left ventricle (for example, with aortic or mitral valve stenosis);
– with unilateral renal artery stenosis in the presence of a second functioning kidney;
– in whom there is or may develop a lack of fluid or electrolytes (including those receiving diuretics);
– with liver cirrhosis and/or ascites;
– who undergo major surgical procedures or who use drugs that cause arterial hypotension during anesthesia.
It is generally recommended that dehydration, hypovolemia, or electrolyte depletion be corrected before initiating treatment (however, in patients with heart failure, such corrective measures should be carefully weighed against the risk of volume overload).
Dual blockade of RAAS
Concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren has been shown to increase the risk of hypotension, hyperkalaemia and deterioration of renal function (including acute renal failure). Therefore, dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended (see sections 5.1 and 5.5).
If such dual blockade therapy is considered absolutely necessary, it should only be used under specialist supervision and with frequent and careful monitoring of renal function, electrolytes and blood pressure.
ACE inhibitors and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.
Transient or persistent heart failure after myocardial infarction
Patients at risk of cardiac or cerebral ischemia in the event of acute hypotension
In the initial phase of treatment, special medical supervision is required.
Elderly patients
See the section "Method of administration and dosage".
Surgery: If possible, treatment with ACE inhibitors such as ramipril should be discontinued 1 day before surgery.
Monitoring of renal function. Renal function should be assessed before and during treatment and the dose adjusted, especially in the first weeks of treatment. Particularly careful monitoring is required when treating patients with impaired renal function (see section "Method of administration and dosage"). There is a risk of deterioration of renal function, especially in patients with congestive heart failure or after kidney transplantation, as well as in cases of renal vascular disease, including patients with hemodynamically significant unilateral renal artery stenosis.
Hypersensitivity/angioedema. Angioedema has been reported in patients treated with ACE inhibitors, including ramipril (see section 4.8). If angioedema develops, Ramipril should be discontinued and emergency treatment should be initiated immediately. The patient should be monitored for at least 12-24 hours and may be discharged after complete resolution of symptoms. Intestinal angioedema has been reported in patients treated with ACE inhibitors, including ramipril (see section 4.8). Patients have complained of abdominal pain (with or without nausea/vomiting).
Concomitant use of ACE inhibitors with racecadotril, mTOR (mammalian target of rapamycin) inhibitors (e.g. sirolimus, everolimus, temsirolimus) or vildagliptin may lead to an increased risk of angioedema (e.g. swelling of the airways or tongue, with or without respiratory distress) (see section 4.5).
Caution should be exercised when initiating racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin in patients already taking an ACE inhibitor.
Anaphylactic reactions during desensitization. When using ACE inhibitors, the likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom and other allergens increases. Therefore, before desensitization, Ramipril should be temporarily discontinued.
Electrolyte balance control: serum potassium. 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 with conditions such as dehydration, acute cardiac decompensation, metabolic acidosis.
ACE inhibitors may cause hyperkalemia because they inhibit aldosterone release. This effect is usually minor in patients with normal renal function. However, in patients with impaired renal function and/or in patients taking potassium supplements (including salt substitutes), potassium-sparing diuretics, other drugs that increase serum potassium (e.g. heparin, trimethoprim or
co-trimoxazole, also known as trimethoprim/sulfamethoxazole) and especially aldosterone antagonists or angiotensin receptor antagonists, hyperkalaemia may occur. Caution should be exercised when potassium-sparing diuretics and angiotensin receptor antagonists are used in patients taking ACE inhibitors. Serum potassium and renal function should be monitored in such patients (see section 4.5).
If concomitant use of the above-mentioned drugs is considered appropriate, regular monitoring of plasma potassium levels is recommended (see section “Interaction with other medicinal products and other types of interactions”).
Electrolyte monitoring: Hyponatremia. Syndrome of inappropriate antidiuretic hormone secretion with subsequent hyponatremia has been observed in some patients treated with ramipril. Regular monitoring of serum sodium levels is recommended in the elderly and in other patients at risk of 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. Closer monitoring is recommended 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”).
Ethnic differences. ACE inhibitors cause angioedema more often in black patients than in non-blacks. The hypotensive effect of ramipril, as with other ACE inhibitors, may be less pronounced in black patients than in non-blacks. This may be because black patients with hypertension are more likely 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.
Ramipril-Teva contains lactose monohydrate, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Sodium content: This medicinal product contains less than 1 mmol (23 mg) sodium per tablet, i.e. essentially ‘sodium-free’.
Use during pregnancy or breastfeeding
Breastfeeding: Because no information is available regarding the use of ramipril during breastfeeding (see section 5.1), this drug is not recommended for use in nursing mothers; alternative treatments with better established safety profiles during lactation are preferable, especially while nursing a newborn or preterm infant.
Ability to influence reaction speed when driving vehicles or other mechanisms
Some side effects (for example, 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 (for example, when driving vehicles or working with other mechanisms).
This is usually possible at the beginning of treatment or when switching from other drugs to treatment with Ramipril-Teva. After taking the first dose or a subsequent increase in dose, it is advisable not to drive or operate other machinery for several hours.
Method of administration and doses
Drug for oral use.
It is recommended to take Ramipril-Teva at the same time each day. The drug can be taken before, during, or after meals, as food does not affect the bioavailability of the drug. Ramipril-Teva tablets should be swallowed whole with water. The tablets can be divided into equal doses. They should not be chewed or crushed.
If it is impossible to use the prescribed dose, ramipril should be used in the appropriate dosage.
Adults
Patients taking diuretics. Hypotension may occur at the beginning of treatment with Ramipril-Teva, the development of which is more likely in patients who are simultaneously receiving diuretics. In such cases, caution is recommended, since these patients may be volume and/or electrolyte depleted.
If possible, it is advisable to discontinue diuretics 2-3 days before starting treatment with Ramipril (see section "Special warnings and precautions for use").
In patients with arterial hypertension who cannot discontinue the diuretic, treatment with Ramipril-Teva should be initiated at a dose of 1.25 mg. Renal function and blood potassium levels should be closely monitored. The dosage of Ramipril-Teva should then be adjusted according to the target blood pressure.
Arterial hypertension
The dose should be selected individually, depending on the characteristics of the patient's condition (see section "Features of use") and the results of control measurements of blood pressure. Ramipril-Teva can be used as monotherapy or in combination with other classes of antihypertensive drugs (see sections "Pharmacodynamics", "Contraindications", "Interaction with other medicinal products and other types of interactions", "Features of use").
Initial dose: Treatment with Ramipril should be initiated gradually, starting with the recommended initial dose of 2.5 mg/day.
In patients with significant activation of the RAAS, a significant decrease in blood pressure may occur after the initial dose. For such patients, the recommended starting dose is 1.25 mg 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-Teva is 10 mg/day. The drug is usually taken once daily.
Prevention of cardiovascular diseases
Initial dose. The recommended initial dose of Ramipril-Teva 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 increase it after 2–3 weeks to the target maintenance dose of 10 mg once daily (see also above for dosing in patients receiving diuretics).
Kidney disease treatment
In patients with diabetes and microalbuminuria
Initial dose. The recommended initial dose of Ramipril-Teva is 1.25 mg once daily.
Dose titration and maintenance dose. Depending on individual tolerability of the drug, the dose is 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.
In patients with diabetes and at least one cardiovascular risk factor
Initial dose. The recommended initial dose of Ramipril-Teva is 2.5 mg once daily.
Dose titration and maintenance dose. Depending on individual tolerability of the drug, the dose is increased during further treatment. After 1-2 weeks of treatment, it is recommended to double the daily dose of Ramipril-Teva to 5 mg, and then to 10 mg after another 2-3 weeks of treatment. The target daily dose is 10 mg.
In patients with non-diabetic nephropathy, as evidenced by macroproteinuria ≥ 3 g/day
Dose titration and maintenance dose. Depending on the individual patient's tolerance of the drug, the dose is 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 stabilized on diuretic therapy, the recommended initial dose is 1.25 mg/day.
Dose titration and maintenance dose. The dose of Ramipril-Teva is titrated by doubling it every 1-2 weeks until a maximum daily dose of 10 mg is reached. The dose should preferably be divided into 2 doses.
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 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.
Dose titration and maintenance dose. The daily dose is then increased by doubling it at intervals of 1–3 days until the target maintenance dose of 5 mg twice daily is reached.
Whenever possible, the maintenance daily dose is divided into 2 doses.
If the dose cannot be increased to 2.5 mg twice daily, treatment should be discontinued. There is currently insufficient experience in patients with severe (NYHA functional class IV) heart failure immediately after myocardial infarction. If a decision is made to treat such patients with this drug, it is recommended to start therapy with a dose of 1.25 mg once daily and any increase should be made with extreme caution (see also above regarding the dosage of the drug for patients receiving diuretics).
Special categories of patients
Patients with renal impairment: The daily dose for patients with renal impairment depends on creatinine clearance (see section 5.1):
– if creatinine clearance is ≥ 60 ml/min, there is no need to adjust the initial dose (2.5 mg/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/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/day, and the maximum daily dose is 5 mg;
– patients with arterial hypertension undergoing hemodialysis: ramipril is excreted to a small extent during hemodialysis; the initial dose is 1.25 mg, and the maximum daily dose is 5 mg; the drug should be taken a few hours after the hemodialysis session.
Patients with hepatic impairment (see section 5.1). Treatment with Ramipril should be initiated under close medical supervision in patients with hepatic impairment, 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.
Children
The drug Ramipril-Teva 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 associated with overdose of ACE inhibitors may include excessive peripheral vasodilation (with marked hypotension, shock), bradycardia, electrolyte imbalance and renal failure. The patient should be closely monitored and symptomatic and supportive therapy should be administered. The proposed treatment measures include initial detoxification (gastric lavage, administration of adsorbents), as well as
