Instructions for use AMPRILAN
The drug is taken orally. It is recommended to swallow the tablet whole, without chewing or crushing, with a sufficient amount of liquid, at the same time every day, regardless of meals.
Adults
In patients taking diuretics,
at the beginning of treatment with Amprilan, arterial hypotension may develop. If possible, diuretic treatment should be discontinued 2-3 days before starting Amprilan therapy. If diuretic treatment is not discontinued in patients with arterial hypertension, Amprilan therapy should be started with a dose of 1.25 mg. Renal function and plasma potassium levels should be monitored. Subsequent doses of Amprilan should be adjusted depending on blood pressure.
Arterial hypertension
The dose should be adjusted individually depending on the patient's condition and blood pressure control.
Amprilan can be used as monotherapy or in combination with other antihypertensive drugs.
Initial dose.
Therapy with Amprilan should be started gradually, with an initial recommended dose of 2.5 mg/day. In patients with a highly activated RAAS, an excessive decrease in blood pressure may be observed after the first dose. These patients are recommended to begin treatment under the supervision of a physician with a dose of 1.25 mg.
Titration and maintenance dose.
The dose can be doubled over an interval of 2 to 4 weeks in order to gradually achieve the target blood pressure level. The maximum permissible dose is 10 mg 1 time / day.
Cardiovascular prevention
Initial dose.
The recommended starting dose of Amprilan is 2.5 mg 1 time/day.
Titration and maintenance dose.
Depending on the tolerability of the drug, the dose should be increased gradually. It is recommended to double the dose after 1 or 2 weeks of therapy and after the next 2 or 3 weeks to increase the maintenance dose to 10 mg 1 time / day.
Treatment of chronic renal failure
Patients with diabetes mellitus and microalbuminuria
Initial dose.
The recommended starting dose of Amprilan is 1.25 mg 1 time/day.
Titration and maintenance dose.
Depending on the tolerability of the drug, the dose should be increased gradually. It is recommended to double the daily dose to 2.5 mg after 2 weeks of therapy and then to 5 mg over the next 2 weeks.
Patients with diabetes mellitus combined with one of the cardiovascular risk factors
Initial dose.
The recommended starting dose of Amprilan is 2 mg 1 time / day.
Titration and maintenance dose.
Depending on the patient’s tolerance of the active substance, the dose should be increased gradually. It is recommended to double the dose after 1 or 2 weeks of therapy to 5 mg and then to 10 mg after and for the next 2 or 3 weeks. The maximum permissible dose is 10 mg/day.
Patients with nondiabetic nephropathy characterized by macroproteinuria ≥3 g/day
Initial dose.
The recommended starting dose of Amprilan is 1.25 mg 1 time/day.
Titration and maintenance dose
. Depending on the tolerability of the drug, the dose should be increased gradually. It is recommended to double the dose after 2 weeks of therapy to 2.5 mg and then to 5 mg over the next 2 weeks.
Symptomatic heart failure
Initial dose.
For patients stabilized on diuretic therapy, the recommended initial dose of Amprilan is 1.25 mg 1 time / day.
Titration and maintenance dose.
The dose of Amprilan should be titrated by doubling every week or two to a maximum dose of 10 mg/day. It is preferable to take the drug 2 times a day.
Secondary prevention after acute myocardial infarction and heart failure
Initial dose.
48 hours after myocardial infarction for clinically and hemodynamically stable patients, the initial dose is 2.5 mg 2 times a day for 3 days. If the initial dose of 2.5 mg is poorly tolerated, then a dose of 1.25 mg 2 times / day should be prescribed for 2 days and further increased to 2.5 mg and 5 mg 2 times / day. If the dose cannot be increased to 2.5 mg 2 times / day, then treatment should be discontinued.
Titration and maintenance dose.
The daily dose should be increased by doubling at intervals of 1-3 days to 5 mg 2 times a day. If possible, the daily dose should be divided into 2 doses daily. If the dose cannot be increased to 2.5 mg 2 times / day, then treatment should be discontinued.
Patients with kidney failure
The daily dose in patients with renal failure should be selected depending on the CC:
- with CC ≥60 ml/min,
no adjustment of the initial dose (2.5 mg daily) is required, the maximum daily dose is 10 mg; - with CC 30-60 ml/min,
no adjustment of the initial dose (2.5 mg daily) is required, the maximum daily dose is 5 mg; - with CC 10-30 ml/min,
the initial dose is 1.25 mg daily, the maximum daily dose is 5 mg; - in patients with arterial hypertension undergoing hemodialysis
: because ramipril is poorly dialyzed, the initial dose is 1.25 mg daily, the maximum daily dose is 5 mg. The drug must be taken several hours after hemodialysis.
Patients with liver failure
Patients with liver failure should begin treatment with Amprilan only under medical supervision, the maximum daily dose is 2.5 mg.
Elderly patients
The initial dose should be reduced and increased gradually due to the risk of side effects, especially in very old and frail patients. A reduction in the initial dose of 1.25 mg should be considered.
Use in children
Amprilan is not recommended for use in children and adolescents under 18 years of age.
, because There is insufficient data on safety and effectiveness.
Amprilan®
Before starting treatment with Amprilan®, it is necessary to eliminate hyponatremia and hypovolemia. In patients who have previously taken diuretics, it is necessary to discontinue them or at least reduce their dose 2-3 days before starting Amprilan® (in this case, the condition of patients with CHF should be carefully monitored due to the possibility of decompensation in them with an increase in BCC).
After taking the first dose of the drug, as well as when increasing its dose and/or the dose of diuretics (especially loop diuretics), it is necessary to ensure careful medical monitoring of the patient for at least 8 hours in order to timely take appropriate measures in the event of a pronounced decrease in blood pressure. If Amprilan® is used for the first time or at a high dose in patients with increased RAAS activity, their blood pressure should be carefully monitored, especially at the beginning of treatment, since these patients have an increased risk of a pronounced decrease in blood pressure (see section “With caution”) .
In case of malignant arterial hypertension and heart failure, especially in the acute stage of myocardial infarction, treatment with Amprilan® should only be started in a hospital setting.
In patients with CHF, taking the drug can lead to the development of a pronounced decrease in blood pressure, which in some cases is accompanied by oliguria or azotemia and rarely by the development of acute renal failure.
Caution should be exercised when treating elderly patients, as they may be particularly sensitive to ACE inhibitors. at the beginning of therapy, it is recommended to monitor renal function indicators (see also section “Method of administration and dosage”).
In patients for whom a decrease in blood pressure may pose a particular risk (for example, patients with atherosclerotic narrowing of the coronary or cerebral arteries), treatment should be initiated under strict medical supervision. Caution should be exercised during physical activity and/or hot weather due to the risk of increased sweating and dehydration with the development of arterial hypotension due to a decrease in blood volume and a decrease in sodium content in the blood serum.
It is not recommended to drink alcohol during treatment with Amprilan®. Transient arterial hypotension is not a contraindication for continuing treatment after stabilization of blood pressure. If severe arterial hypotension reoccurs, the dose should be reduced or the drug discontinued.
The simultaneous use of Amprilan® with drugs containing aliskiren or ARA II, leading to double blockade of the RAAS, is not recommended due to the risk of a pronounced decrease in blood pressure, the development of hyperkalemia and deterioration of renal function compared with monotherapy.
The simultaneous use of ACE inhibitors with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate to severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients (see Sections “Contraindications” and “Interaction with other drugs”). The simultaneous use of ACE inhibitors with ARA II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see sections “Contraindications” and “Interaction with other drugs”).
In patients treated with ACE inhibitors. Cases of angioedema of the face, extremities, lips, tongue, pharynx or larynx have been observed. If swelling occurs in the face (lips, eyelids) or tongue, or difficulty swallowing or breathing, the patient should immediately stop taking the drug. Angioedema, localized in the area of the tongue, pharynx or larynx (possible symptoms: difficulty swallowing or breathing), can be life-threatening and requires urgent measures to relieve it: subcutaneous administration of 0.3-0.5 mg or intravenous drip of 0.1 mg of epinephrine (adrenaline) (under the control of blood pressure, heart rate and electrocardiogram (ECG) followed by the use of glucocorticosteroids (intravenous, intramuscular or orally); intravenous administration of antihistamines (H1- and H2-histamine receptor antagonists) is also recommended, and in case of insufficiency of inhibitors C1-esterase enzyme, C1-esterase enzyme inhibitors may be considered in addition to epinephrine (adrenaline).The patient should be hospitalized and monitored until symptoms are completely relieved, but for at least 24 hours.
In patients receiving ACE inhibitors, cases of intestinal angioedema, which was manifested by abdominal pain with or without nausea and vomiting, were observed, in some cases, angioedema of the face was also observed simultaneously. If a patient develops the symptoms described above during treatment with ACE inhibitors, the possibility of developing intestinal angioedema should be considered when making a differential diagnosis.
Treatment aimed at desensitization to insect venom (for example, bees, wasps), and concurrent use of ACE inhibitors can initiate anaphylactic and anaphylactoid reactions (for example, marked decrease in blood pressure, shortness of breath, vomiting, allergic skin reactions), which can sometimes be life-threatening . During treatment with ACE inhibitors, hypersensitivity reactions to insect venom (for example, bees, wasps) develop faster and are more severe. If desensitization to insect venom is necessary, the ACE inhibitor should be temporarily replaced with an appropriate drug of a different class.
Life-threatening, rapidly developing anaphylactoid reactions, sometimes leading to shock, have been described with the use of ACE inhibitors during hemodialysis or hemofiltration using certain high-flux membranes (for example, polyacrylonitrile membranes) (see also membrane manufacturer's instructions). The simultaneous use of Amprilan® and the use of this type of membrane, for example, for emergency hemodialysis or hemofiltration, should be avoided. In this case, it is preferable to use other membranes or discontinue ACE inhibitors. Similar reactions were observed with LDL apheresis using dextran sulfate. Therefore, this method should not be used in patients receiving ACE inhibitors. In patients with impaired liver function, the response to treatment with Amprilan® may be either enhanced or weakened. In addition, in patients with severe liver cirrhosis with edema and/or ascites, significant activation of the RAAS is possible, so special care should be taken when treating these patients (see also section "Dosage and Administration").
Monitoring the content of electrolytes in blood plasma
Hyperkalemia
ACE inhibitors may cause hyperkalemia because they inhibit the release of aldosterone. This effect is usually minor in patients with normal renal function. However, in patients with impaired renal function and/or in patients concomitantly taking drugs containing potassium (including potassium-containing salt substitutes), potassium-sparing diuretics, trimethoprim or co-trimoxazole, also known as trimethoprim + sulfamethoxazole, and in particular aldosterone antagonists or ARBs II, hyperkalemia may develop. The risk group for developing hyperkalemia also includes elderly patients (over 70 years of age), patients with decompensated diabetes mellitus or patients in a state of dehydration, patients with acute heart failure, metabolic acidosis.
Potassium-sparing diuretics and ARB II should be used with caution in patients receiving ACE inhibitors, and serum potassium levels and renal function should be regularly monitored (see section "Interaction with other drugs").
Some patients receiving ramipril experienced SNA ADH with subsequent development of hyponatremia. It is recommended to regularly monitor plasma sodium levels in elderly patients and other patients at risk of developing hyponatremia.
Before surgery (including dental surgery), it is necessary to warn the surgeon/anesthesiologist about the use of ACE inhibitors.
It is recommended to carefully monitor newborns whose mothers used ACE inhibitors during pregnancy. to detect arterial hypotension, oliguria and hyperkalemia. In oliguria, it is necessary to maintain blood pressure and renal perfusion by administering appropriate fluids and vasoconstrictors. These neonates are at risk of developing oliguria and neurological disorders, possibly due to reduced renal and cerebral blood flow due to the reduction in blood pressure caused by ACE inhibitors.
Cough
When using the drug Amprilan®, a dry, unproductive, prolonged cough may occur, which disappears after stopping the use of ACE inhibitors (including ramipril), which must be taken into account in the differential diagnosis of cough during the use of an ACE inhibitor.
Ethnic characteristics
The drug Amprilan®, like other ACE inhibitors. has a less pronounced antihypertensive effect in patients of the Negroid race compared to representatives of other races.
Amprilan® should be prescribed with caution to patients of the Black race due to a higher risk of developing angioedema.
Patients after kidney transplantation
There is insufficient experience with the use of ramipril in patients who have recently undergone kidney transplantation.
Monitoring laboratory parameters before and during treatment with Amprilan
®
(up to 1 time per month in the first 3-6 months of treatment)
Monitoring kidney function (determining serum creatinine concentrations)
When treating with ACE inhibitors, it is recommended to monitor renal function in the first weeks of treatment and subsequently. Particularly careful monitoring is required in patients with acute heart failure and CHF, impaired renal function, after kidney transplantation, patients with renovascular diseases, including patients with hemodynamically significant unilateral renal artery stenosis in the presence of two kidneys (in such patients, even a slight increase in serum creatinine concentration may be indicator of decreased kidney function).
Monitoring of hematological parameters (hemoglobin, number of leukocytes, erythrocytes, platelets, leukocyte formula)
It is recommended to monitor the complete blood count to identify possible leukopenia. More regular monitoring is recommended at the beginning of treatment and in patients with impaired renal function, as well as in patients with connective tissue diseases or in patients simultaneously receiving other drugs that can change the peripheral blood picture (see section "Interaction with other drugs") . Monitoring the number of leukocytes is necessary for the early detection of leukopenia, which is especially important in patients with an increased risk of its development, as well as at the first signs of infection. If neutropenia is detected (the number of neutrophils is less than 2000/μl), discontinuation of treatment with ACE inhibitors is required.
If symptoms due to leukopenia appear (for example, fever, swollen lymph nodes, tonsillitis), urgent monitoring of the peripheral blood picture is necessary. If signs of bleeding appear (tiny petechiae, red-brown rashes on the skin and mucous membranes), monitoring the number of platelets in the peripheral blood is also necessary.
Determination of the activity of “liver” enzymes, the concentration of bilirubin in blood serum
If jaundice or a significant increase in the activity of liver enzymes in the blood plasma appears, treatment with Amprilan® should be stopped and medical supervision of the patient should be provided.
Special information on excipients
Amprilan® contains lactose and is therefore contraindicated in patients with lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
Amprilan, 30 pcs., 1.25 mg, tablets
At the beginning of treatment, renal function should be assessed. Renal function should be carefully monitored in patients with impaired renal function, heart failure, bilateral renal artery stenosis or arterial stenosis of a solitary kidney, as well as in patients after kidney transplantation.
Liver failure
In rare cases, during the use of ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant liver necrosis develops, sometimes with a fatal outcome. If jaundice appears or a significant increase in the activity of liver transaminases while taking ACE inhibitors, the use of Amprilan® should be discontinued.
In patients with uncomplicated arterial hypertension, symptomatic arterial hypotension rarely develops after taking the first dose of the drug. The risk of developing arterial hypotension is increased in the following patients:
- with severe CHF: treatment begins with the lowest possible dose of Amprilan® (1.25 mg);
- those taking diuretics: if possible, it is necessary to cancel the diuretic in advance or reduce its dose; treatment begins with a minimum dose of Amprilan® (1.25 mg);
- with the risk of developing hypovolemia due to insufficient fluid intake, diarrhea, vomiting or increased sweating in conditions of insufficient compensation for salt and fluid loss. It is usually recommended to adjust the blood volume before starting treatment, but if these conditions become clinically significant, treatment with Amprilan® can be started and/or continued with a minimum dose (1.25 mg) and under medical supervision.
Aortic stenosis/mitral stenosis/HOCM
ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction and aortic and/or mitral stenosis.
Neutropenia/agranulocytosis
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.
Ramipril 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. These patients may develop severe infections that do not respond to intensive antibiotic therapy. When using ramipril, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that if any signs of an infectious disease appear (sore throat, fever), consult a doctor immediately.
Hyperkalemia
May develop during treatment with ACE inhibitors, incl. and ramipril. Risk factors for hyperkalemia are renal failure, old age, diabetes mellitus, some concomitant conditions (decrease in blood volume, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as drugs potassium or potassium-containing substitutes for table salt and the use of other drugs that increase the content of potassium in the blood plasma (for example, heparin). Hyperkalemia can cause serious heart rhythm problems, sometimes fatal.
Potassium-sparing diuretics and potassium supplements
The combined use of Amprilan® and potassium-sparing diuretics, as well as potassium preparations and potassium-containing table salt substitutes is not recommended.
Surgery/general anesthesia
The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect.
It is recommended to stop taking ACE inhibitors, incl. ramipril, 12 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors.
Cough
During therapy with an ACE inhibitor, a dry 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 taking an ACE inhibitor.
Anaphylactoid reactions during desensitization procedures
There are isolated reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the venom of hymenoptera insects (bees, wasps). 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
In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during 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
Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg AN69®). Therefore, it is advisable to use a different type of membrane or use an antihypertensive drug of a different pharmacotherapeutic group.
Impact on the ability to drive a car or perform work that requires increased speed of physical and mental reactions.
During the treatment period, care must be taken when engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, because Dizziness, drowsiness, confusion and other side effects are possible.
