Ramazid N
Ramipril. At the beginning of treatment, renal function should be assessed. It is necessary to carefully monitor renal function during treatment with ramipril, especially in patients with weakened renal function, with damage to the renal vessels (for example, clinically insignificant renal artery stenosis or hemodynamically significant stenosis of the artery of a solitary kidney); heart failure. The risk of hypersensitivity and allergy-like (anaphylactoid) reactions is increased in patients concomitantly taking ACE inhibitors and undergoing hemodialysis using AN69 dialysis membranes. Similar reactions have been observed with low-density lipoprotein apheresis using dextran sulfate, so this method should be avoided during treatment with ACE inhibitors. During treatment with ramipril in patients with impaired renal function, especially with simultaneous treatment with diuretics, serum urea and creatinine levels may increase. In this case, treatment should be continued with lower doses of ramipril or the drug should be discontinued. In patients with impaired renal function, the risk of hyperkalemia increases. In patients with impaired liver function, due to a decrease in the activity of liver enzymes, the metabolism of ramipril and the formation of an active metabolite may be slowed down. In this regard, treatment of such patients should only be started under strict medical supervision. Caution must be exercised when prescribing ramipril to patients on a low-salt or salt-free diet (increased risk of arterial hypotension). In patients with a reduced circulating blood volume (as a result of diuretic therapy), during dialysis, with diarrhea and vomiting, symptomatic hypotension may develop. 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. In patients undergoing major surgery or receiving other agents that cause hypotension during general anesthesia, ramipril may cause blockade of angiotensin II formation due to compensatory release of renin. If the physician associates the development of arterial hypotension with the mechanism mentioned above, arterial hypotension can be corrected by increasing blood plasma volume. In rare cases, agranulocytosis, erythrocytopenia, thrombocytopenia, hemoglobinemia or bone marrow suppression have been observed during treatment with ACE inhibitors. At the beginning and during treatment, it is necessary to monitor the number of white blood cells to detect possible neutropenia/agranulocytosis. More frequent monitoring is recommended in patients with renal failure, with connective tissue diseases (eg, systemic lupus erythematosus or scleroderma) and in patients concomitantly taking medications that affect hematopoiesis. Counting blood cells should also be carried out if clinical signs of neutropenia/agranulocytosis and increased bleeding occur. In patients with arterial hypertension, when treated with ramipril, an increase in serum potassium levels is rarely observed. The risk of hyperkalemia increases with chronic heart failure, simultaneous treatment with potassium-sparing diuretics (spironolactone, amiloride, triamterene) and the prescription of potassium supplements. When using ACE inhibitors during desensitization therapy to wasp or bee venom, anaphylactoid reactions (eg, hypotension, shortness of breath, vomiting, skin rash) may occur, which can be life-threatening. Hypersensitivity reactions may occur from insect bites (eg bees or wasps). If it is necessary to carry out desensitizing treatment with bee or wasp venom, it is necessary to discontinue ACE inhibitors and continue treatment with suitable drugs from other groups.
During treatment with Ramazid N, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretic drugs). Patients are advised to refrain from driving or operating machinery until the response to treatment is clear.
Hydrochlorothiazide
To prevent K+ and Mg2+ deficiency, potassium-sparing diuretics, K+ and Mg2+ salts are prescribed. Regular monitoring of plasma levels of potassium, glucose, uric acid, lipids and creatinine is necessary.
Ramazid H
The simultaneous use of Ramazid N (12.5/5 mg) with drugs containing aliskiren or with angiotensin II receptor antagonists, leading to double blockade of the RAAS, is not recommended due to the risk of an excessive decrease in blood pressure, the development of hyperkalemia and deterioration of renal function. The simultaneous use of Ramazid N (12.5/5 mg) with drugs containing aliskiren in patients with diabetes mellitus and/or renal failure with creatinine clearance <60 ml/min is contraindicated (see section "Contraindications" and "Interaction with other medicines").
Angioedema of the face, neck or limbs
(see section "Side effects")
During treatment with ACE inhibitors, mainly after taking the first dose, cases of angioedema have been observed. If angioedema develops during treatment with an ACE inhibitor, immediate cessation of its use is required.
Since angioedema involving the larynx can be fatal, in case of swelling of the face, limbs, lips, tongue or vocal cords and, especially, the development of stridorous breathing, you should immediately stop taking Ramazide N (12.5/5 mg) and immediately begin treatment aimed at relieving angioedema. In cases where the swelling is localized to the face and lips, the condition usually resolves without treatment, although antihistamines may be used to relieve symptoms.
If swelling spreads to the tongue, vocal cords or pharynx, airway obstruction is possible, in such cases it is necessary to immediately begin appropriate treatment (including immediate subcutaneous or slow intravenous administration of epinephrine (adrenaline) under ECG and blood pressure monitoring). Hospitalization is recommended for at least 12-24 hours and discharge from the hospital only after complete relief of the symptoms of angioedema.
Angioedema of the small intestine
In patients receiving ACE inhibitors, the development of angioedema of the small intestine, which was manifested by abdominal pain (with or without nausea or vomiting), was reported, and in some cases angioedema of the face was simultaneously observed. Diagnosis is made using abdominal computed tomography, ultrasound, or surgery. Symptoms of intestinal angioedema resolved after discontinuation of the ACE inhibitor.
Choroidal effusion/acute myopia/acute angle-closure glaucoma
Sulfonamides and their derivatives can cause an idiosyncratic reaction leading to the development of choroidal effusion with visual field impairment, acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or eye pain and usually occur within hours to weeks of starting the drug. If left untreated, an acute attack of angle-closure glaucoma can lead to permanent vision loss. First of all, it is necessary to stop taking the drug as quickly as possible. If intraocular pressure remains uncontrolled, emergency medical treatment or surgery may be required. Risk factors for the development of an acute attack of angle-closure glaucoma are a history of allergic reactions to sulfonamide derivatives and penicillins.
Cough
When taking the drug Ramazid N (12.5/5 mg), a “dry” cough may occur, which usually disappears after discontinuation of the drug. This possibility must be taken into account when making a differential diagnosis of cough (see section “Side effects”).
Anaphylactoid reactions to ACE inhibitors
Life-threatening, rapid-onset anaphylactoid reactions, sometimes leading to shock, have been described with ACE inhibitors during hemodialysis using certain high-flux membranes (eg, polyacrylonitrile membranes) (see also membrane manufacturer's instructions). It is necessary to avoid the combined use of the drug Ramazid N (12.5/5 mg) and this type of membrane, for example, for urgent hemodialysis or hemofiltration. In this case, it is preferable to use other types of membranes or avoid taking ACE inhibitors.
Similar reactions were observed with low-density lipoprotein apheresis using dextran sulfate. These reactions were avoided by temporarily stopping ACE inhibitor therapy before performing the next apheresis. Antihistamines are ineffective for treating these reactions. There have been isolated reports of patients with prolonged life-threatening anaphylactoid reactions that occurred during desensitizing treatment with venom from bees, wasps, etc. In some patients, these reactions were avoided by preliminary temporary withdrawal of ACE inhibitors for a period of at least 24 hours.
Hypersensitivity reactions to hydrochlorothiazide do not depend on a history of allergies or bronchial asthma.
Excessive decrease in blood pressure
After using ramipril, usually after the first or second dose, or after increasing the dose, an excessive decrease in blood pressure is possible, which is most likely in patients whose circulating blood volume has been reduced as a result of diuretic therapy, limited dietary salt intake, dialysis, diarrhea, vomiting or excessive sweating.
It is generally recommended that dehydration, hypovolemia, and hyponatremia be corrected before starting the drug (however, in patients with heart failure, volume replacement should be carried out with great caution, as there is a risk of decompensation due to excessive volume load).
A transient excessive decrease in blood pressure is not a contraindication for continuing treatment after stabilization of blood pressure. In case of repeated excessive decrease in blood pressure, the dose should be reduced or the drug discontinued.
Patients with RAAS activation
In conditions in which the RAAS is activated and/or renal function depends on its activity (see section "Precautions"), with ACE inhibition there is an increased risk of a pronounced decrease in blood pressure and impaired renal function. Therefore, in such cases, at the beginning of treatment or at the beginning of an increase in the initially taken dose, careful monitoring of blood pressure is required until a further decrease in blood pressure is no longer expected.
In patients with severe heart failure (including those accompanied by renal failure), ACE inhibitor therapy may cause an excessive decrease in blood pressure and be accompanied by oliguria and/or progressive azotemia with acute renal failure, including death. In such patients, initiation or continuation of treatment with Ramazid N (12.5/5 mg) should be carried out only after taking measures against an excessive decrease in blood pressure and deterioration of renal function.
Patients for whom an excessive decrease in blood pressure may be particularly dangerous
An excessive decrease in blood pressure is especially dangerous for patients with coronary heart disease or severe cerebral atherosclerosis, since in this case the development of myocardial infarction or stroke is possible (see section “With caution”). Such patients are subject to strict monitoring at the beginning of treatment and when increasing the dose of the drug.
Patients with dehydration
All patients should be warned that dehydration due to increased sweating (including during hot weather or physical activity), vomiting, diarrhea can lead to an excessive decrease in blood pressure, and in these cases the question of the dose of ramipril and hydrochlorothiazide used should be decided by a doctor .
Taking alcohol (ethanol) during treatment with Ramazid N (12.5/5 mg)
During treatment with Ramazid N (12.5/5 mg), it is not recommended to drink alcohol (ethanol) (see section “Interaction with other drugs”). In cases of excessive decrease in blood pressure, it is necessary to lay the patient with his legs elevated, and, if necessary, start intravenous infusion of 0.9% sodium chloride solution to replenish the circulating blood volume (circulating blood volume).
Surgery and anesthesia
Before surgical interventions (including dental), it is necessary to warn the surgeon/anesthesiologist about taking ACE inhibitors. If an excessive decrease in blood pressure occurs during anesthesia, it can be corrected by replenishing the blood volume.
Thiazide diuretics may enhance the effects of tubocurarine.
It is recommended that treatment with ACE inhibitors, including ramipril, be discontinued (if possible) one day before surgery.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs that act through inhibition of the RAAS, so Ramazide N (12.5/5 mg) is not the drug of choice for the treatment of primary hyperaldosteronism.
Non-melanoma skin cancer
Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide use and an increased risk of nonmelanoma skin cancer (NMSC) basal cell carcinoma and squamous cell carcinoma. The risk of developing NMSC increased with increasing total (cumulative) dose of hydrochlorothiazide. A possible mechanism for the development of NMSC is the photosensitizing effect of hydrochlorothiazide.
Patients taking hydrochlorothiazide as monotherapy or in combination with other drugs should be aware of the risk of developing NMSC. It is recommended that such patients undergo regular skin examination to identify any new suspicious lesions as well as changes in existing skin lesions.
Any suspicious skin changes should be reported to your doctor immediately.
Suspicious areas of skin should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.
To minimize the risk of developing NMSC, patients should be advised to follow preventive measures, such as limiting exposure to sunlight and UV rays, and using appropriate protective equipment.
In patients with a history of NMSC, it is recommended to reconsider the use of hydrochlorothiazide.
Monitoring hematological parameters
When taking the drug Ramazid N (12.5/5 mg), it is recommended to monitor the number of leukocytes to identify possible leukopenia. Regular monitoring is recommended at the beginning of treatment and in patients with impaired renal function, connective tissue diseases (systemic lupus erythematosus, scleroderma) or in patients receiving other drugs that can change the peripheral blood picture (see section "Side effects", "Interaction with other medicines"). If symptoms due to leukopenia appear (for example, fever, enlarged 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.
Monitoring liver function
A complete liver function test and other liver tests should be performed if patients develop the following symptoms suggestive of liver dysfunction: flu-like symptoms occurring in the first weeks or months of treatment (such as fever, malaise, muscle pain, skin rash, or adenopathy indicating reactions hypersensitivity), abdominal pain, nausea or vomiting, loss of appetite, jaundice, itching or other unexplained symptoms. If liver dysfunction is confirmed, you should stop taking Ramazid N (12.5/5 mg) and, if necessary, prescribe appropriate treatment.
In patients with impaired liver function or with progressive liver diseases, the use of thiazide diuretics requires caution, since in such patients even minimal disturbances in water and electrolyte balance can provoke the development of hepatic coma.
Controlled clinical studies involving patients with cirrhosis and/or impaired liver function, who should determine the state of liver function before starting the drug and regularly monitor it during treatment.
Monitoring kidney function
Due to suppression of the RAAS, renal function may deteriorate in predisposed patients; this risk increases with the simultaneous use of diuretics.
It is recommended to carefully monitor renal function in the first weeks of treatment and thereafter, especially in the following groups of patients:
- patients with heart failure;
- patients with renovascular diseases, including hemodynamically significant unilateral renal artery stenosis (in such patients, even a slight increase in serum creatinine concentrations may be a manifestation of a unilateral decrease in renal function);
- patients with impaired renal function;
- patients after kidney transplantation.
In patients with renal failure, special caution is required when treating with Ramazid N (12.5/5 mg), and in these cases lower doses of the drug are used (see section "Dosage and Administration").
Hydrochlorothiazide may promote or worsen azotemia. Cumulative effects of the drug are possible in patients with impaired renal function. If increasing azotemia and oliguria develop during treatment of severe progressive renal disease, diuretic therapy should be discontinued.
Insufficient experience has been gained with the use of Ramazid N (12.5/5 mg) in patients with severe renal impairment (creatinine clearance less than 30 ml/min per 1.73 m2 body surface area) and in patients on hemodialysis.
Monitoring electrolytes and serum glucose concentrations
Treatment with Ramazid N (12.5/5 mg) requires regular monitoring of sodium, potassium, calcium, uric acid in the blood serum and blood glucose. Patients with impaired renal function and impaired water and electrolyte balance require regular monitoring of potassium levels in the blood serum.
Other Cautions
Thiazide diuretics can reduce blood concentrations of protein-bound iodine without causing signs of thyroid dysfunction. Thiazide diuretics may cause a transient and small increase in serum calcium in the absence of known disorders of calcium metabolism. Severe hypercalcemia may indicate latent hyperparathyroidism. Before assessing parathyroid function, thiazide diuretics should be discontinued. Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, and concomitant use of drugs to treat hypokalemia or other drugs that can increase serum potassium levels (see section "Interaction with other drugs").
Patients should be cautioned not to use salt substitutes containing potassium without first consulting their healthcare provider. It should be taken into account that when using hydrochlorothiazide, a positive doping test is possible.
Ramazid N, 2.5 mg+12.5 mg, tablets, 100 pcs.
Ramipril.
At the beginning of treatment, renal function should be assessed. It is necessary to carefully monitor renal function during treatment with ramipril, especially in patients with weakened renal function, with damage to the renal vessels (for example, clinically insignificant renal artery stenosis or hemodynamically significant stenosis of the artery of a solitary kidney); heart failure.
The risk of hypersensitivity and allergy-like (anaphylactoid) reactions is increased in patients concomitantly taking ACE inhibitors and undergoing hemodialysis using AN69 dialysis membranes. Similar reactions have been observed with low-density lipoprotein apheresis using dextran sulfate, so this method should be avoided during treatment with ACE inhibitors.
During treatment with ramipril in patients with impaired renal function, especially with simultaneous treatment with diuretics, serum urea and creatinine levels may increase. In this case, treatment should be continued with lower doses of ramipril or the drug should be discontinued. In patients with impaired renal function, the risk of hyperkalemia increases.
In patients with impaired liver function, due to a decrease in the activity of liver enzymes, the metabolism of ramipril and the formation of an active metabolite may be slowed down. In this regard, treatment of such patients should only be started under strict medical supervision.
Caution must be exercised when prescribing ramipril to patients on a low-salt or salt-free diet (increased risk of arterial hypotension). In patients with a reduced circulating blood volume (as a result of diuretic therapy), during dialysis, with diarrhea and vomiting, symptomatic hypotension may develop.
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.
In patients undergoing major surgery or receiving other agents that cause hypotension during general anesthesia, ramipril may cause blockade of angiotensin II formation due to compensatory release of renin. If the physician associates the development of arterial hypotension with the mechanism mentioned above, arterial hypotension can be corrected by increasing blood plasma volume.
In rare cases, agranulocytosis, erythrocytopenia, thrombocytopenia, hemoglobinemia or bone marrow suppression have been observed during treatment with ACE inhibitors. At the beginning and during treatment, it is necessary to monitor the number of white blood cells to detect possible neutropenia/agranulocytosis. More frequent monitoring is recommended in patients with renal failure, with connective tissue diseases (eg, systemic lupus erythematosus or scleroderma) and in patients concomitantly taking medications that affect hematopoiesis. Counting blood cells should also be carried out if clinical signs of neutropenia/agranulocytosis and increased bleeding occur.
In patients with arterial hypertension, when treated with ramipril, an increase in serum potassium levels is rarely observed. The risk of hyperkalemia increases with chronic heart failure, simultaneous treatment with potassium-sparing diuretics (spironolactone, amiloride, triamterene) and the prescription of potassium supplements.
When using ACE inhibitors during desensitization therapy to wasp or bee venom, anaphylactoid reactions (eg, hypotension, shortness of breath, vomiting, skin rash) may occur, which can be life-threatening. Hypersensitivity reactions may occur from insect bites (eg bees or wasps). If it is necessary to carry out desensitizing treatment with bee or wasp venom, it is necessary to discontinue ACE inhibitors and continue treatment with suitable drugs from other groups.
During treatment with Ramazid N, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretic drugs). Patients are advised to refrain from driving or operating machinery until the response to treatment is clear.
Hydrochlorothiazide.
To prevent K+ and Mg2+ deficiency, potassium-sparing diuretics, K+ and Mg2+ salts are prescribed. Regular monitoring of plasma levels of potassium, glucose, uric acid, lipids and creatinine is necessary.
