Simultaneous use of the Tritace drug "plus with preparations containing aliskiren, or with antagonists of angiotensin II receptors, resulting in a double blockade of RAAS, is not recommended due to the risk of excessive reduction in blood pressure, the development of hyperkalemia and impaired renal function. The simultaneous use of Tritace plus preparations containing aliskiren, in patients with diabetes mellitus and / or renal insufficiency with creatinine clearance <60 ml / min is contraindicated (see the sections "Contraindications" and "Interaction with other drugs"). Simultaneous use with antagonists of receptors for angiotensin II in patients with diabetic nephropathy is contraindicated (see.sections "Contraindications" and "Interaction with other medicinal products").
Angioedema, edema of the face, neck or extremities (see section "Side effect"). In the treatment of ACE inhibitors, mainly after the first dose, cases of angioedema have been observed. When angioedema develops during treatment with an ACE inhibitor, an immediate discontinuation of its administration is required.
Since angioedema with involvement of the larynx can lead to death, in case of edema of the face, extremities, lips, tongue or vocal cords and, especially, the development of stridor breathing, immediately stop taking Tritace plus and immediately begin treatment aimed at stopping angioedema. In cases where the edema is localized on the face and lips, this condition is usually resolved without treatment, however, antihistamines can be used to relieve symptoms. When swelling is spreading on the tongue, vocal cords or throat, airway obstruction is possible, in such cases it is necessary to begin promptly appropriate treatment (including immediate subcutaneous or slow intravenous injection of epinephrine (adrenaline) under ECG and blood pressure control).Recommended hospitalization for at least 12-24 hours and discharge from the hospital only after complete relief of symptoms of angioedema.
Angioedema of the thin
intestines
Patients receiving ACE inhibitors reported the development of angioedema of the small intestine, which manifested itself in abdominal pain (with or without nausea or vomiting), while in some cases angioedema was observed simultaneously. The diagnosis is established by means of computed tomography of the abdominal cavity, ultrasound examination or at the time of surgical intervention. Symptoms of angioedema of the bowel passed after the cessation of the ACE inhibitor.
Acute myopia and secondary acute closed angle glaucoma
Hydrochlorothiazide is a sulfonamide derivative. Sulfonamide and sulfonamide derivatives can cause idiosyncrasy reactions leading to the development of transient myopia and acute closed-angle glaucoma, the symptoms of which are acute reduction in visual acuity or pain in the eyes. They usually occur within a few hours to several weeks after starting the drug.In the absence of treatment, acute closed-angle glaucoma can lead to persistent loss of vision. It is necessary to stop taking the drug as soon as possible. Emergency medical or surgical treatment may be required if the intraocular pressure remains uncontrolled. Risk factors for the development of acute myopia or secondary closed-angle glaucoma are anamnestic indications of allergy to sulfonamide derivatives or penicillins.
Cough
When taking Tritace Plus, there may be a "dry" cough that usually disappears after the drug is discontinued. Such a probability should be taken into account when making a differential diagnosis of coughing (see section "Side effect").
Anaphylactoid reactions to ACE inhibitors
With the administration of ACE inhibitors, life-threatening, rapidly developing anaphylactoid reactions sensitivity, sometimes up to the development of shock during hemodialysis with the use of certain high-flow membranes (for example, polyacrylonitrile membranes) (see also instructions manufacturers of membranes).
It is necessary to avoid joint administration of Tritace® plus plus such membranes, for example, for urgent hemodialysis or hemofiltration. In this case, it is preferable to use other types membranes or exclusion of ACE inhibitors. Similar reactions were observed in the apheresis of low-density lipoproteins using dextran sulfate. These reactions could be avoided with the temporary cessation of therapy with an ACE inhibitor before each next apheresis. Antihistamines drugs are not effective for the therapy of these reactions.
Separate reports were received of patients with long life-threatening anaphylactoid reactions that occurred during desensitizing treatment with bee venom, wasps, etc. In some patients, these reactions could be avoided by preliminary provisional abolition of ACE inhibitors for a period of at least 24 hours. Reactions increased sensitivity to hydrochlorothiazide does not depend on the presence in the history of allergy or bronchial asthma.
Excessive BP reduction
After using ramipril, usually after the first or second dose, or after increasing the dose possibly excessive decrease in blood pressure, which is most likely patients with volume circulating blood was reduced in the result of diuretic therapy, limited income table salt with food, dialysis, diarrhea, vomiting, or profuse sweating.
It is generally recommended that dehydration, hypovolemia and hyponatremia be corrected before starting the use of the drug (however, in patients with heart failure, replenishment of the circulating blood volume should be carried out with great care, since there is a risk of decompensation due to excessive volume loading). Transient excessive decrease in blood pressure is not a contraindication for continuing treatment after stabilization of blood pressure. In the case of repeated excessive decrease in blood pressure should reduce the dose or cancel the drug.
Patients with the activation of RLAS In conditions in which RAAS activation occurs and / or kidney function depends on its activity (see the section "With caution"), with the inhibition of ACE, there is an increased risk of a marked decrease in blood pressure and renal dysfunction. Therefore, in such cases, at the beginning of the treatment or at the beginning of the cases at the beginning of the treatment or at the beginning increase initially of the dose to be taken, careful monitoring of blood pressure is required until the time when no further BP reduction is expected.
In patients with severe heart failure (including those accompanied by renal insufficiency), therapy with an ACE inhibitor may cause an excessive decrease in blood pressure and be accompanied by oliguria and / or progressive azotemia with acute renal failure, up to a lethal outcome. In such patients, initiation of treatment with Tritatse * plus or its continuation should be carried out only after taking measures against a sharp decrease in blood pressure and impaired renal function.
Patients for whom excessive BP reduction represents a particular hazard A particular danger is the excessive reduction in blood pressure for patients with coronary heart disease or with severe atherosclerosis of cerebral vessels, as in this case it is possible to develop a myocardial infarction or stroke (see the section "With caution"). Such patients are subject to strict observation at the beginning of treatment and with an increase in the dose of the drug.
Patients with dehydration All patients should be warned that dehydration due to increased sweating (including,and in hot weather or physical exertion), vomiting, diarrhea can lead to excessive blood pressure lowering, and in these cases the question of the applied doses of ramipril and hydrochlorothiazide should be decided by the doctor.
The intake of alcohol (ethanol) during treatment with Tritace® a plus During treatment with Tritace ^ plus, it is not recommended to drink alcohol (ethanol) (see section "Interaction with other drugs").
In case of excessive reduction in blood pressure, it is necessary to lay the patient with raised legs, and, with infusion of 0.9% sodium chloride solution to replenish BCC (circulating blood volume).
Surgery and anesthesia
Before surgical interventions (including dental) it is necessary to alert the surgeon / anesthesiologist about taking ACE inhibitors. If an excessive decrease in blood pressure occurs during anesthesia, it can be corrected by replenishing the BCC.
Thiazide diuretics can enhance the effects of tubocurarine. It is recommended that treatment with ACE inhibitors, including ramipril, was terminated (if possible) one day before surgical intervention.
Primary hyperaldosteronism Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs acting through inhibition of RAAS. Therefore, the drug Tritace plus is not a drug of choice for the treatment of primary hyperaldosteronism.
Control of hematological parameters When taking the drug Tritace® plus is recommended to control leukocytes to detect possible leukopenia. More frequent 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 capable of altering the picture of peripheral blood (see "Side effect", "Interaction with other medicinal products ").
When symptoms appear due to leukopenia (eg, fever, enlarged lymph nodes, tonsillitis), urgent monitoring of the peripheral blood picture is necessary. In case of signs of bleeding (the smallest petechiae, red-brown rashes on the skin and mucous membranes), it is also necessary to control the amount of platelets in the peripheral blood.
Control of the functional state of the liver Required conduct a complete liver function test and other liver tests when patients develop the following symptoms that are suspicious of their violation: flu-like symptoms that occur in the first weeks or months of treatment (such as fever, malaise, muscle pain, skin rash, or adenopathy, sensitivity), abdominal pain, nausea or vomiting, loss of appetite, jaundice, pruritus, or other symptoms that have no other explanation. In case of confirmation of the liver, you should stop taking Tritace® plus and, if necessary, prescribe appropriate treatment.
In patients with impaired hepatic function or with progressive liver diseases, the use of thiazides requires caution, since in such patients, even minimal disturbances of the water-electrolyte balance can provoke a hepatic coma.
Controlled clinical Studies involving patients with cirrhosis and / or liver dysfunction are not available. With special care, Tritace® plus should be used in patients with pre-existing liver function impairment,which before the application of the drug should determine the status of liver function and regularly monitor it during treatment.
Control of kidney function Due to the suppression of RAAS in predisposed patients possibly worsening kidney function, this risk increases with the simultaneous use of diuretics.
It is recommended that the kidney function be carefully monitored in the first weeks of treatment and thereafter, especially in the following patient groups:
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 reduction in renal function);
patients with impaired renal function;
patients after kidney transplantation.
In patients with renal insufficiency, special care is required in the treatment with Tritace plus, and in these cases smaller doses are used (see section "Method of administration and dose").
Hydrochlorothiazide may promote development or enhance azotemia.Cumulative effects of the drug are possible in patients with impaired renal function. If increasing azotemia and oliguria develop during treatment of a serious progressive kidney disease, diuretic therapy should be discontinued. Insufficient experience has been accumulated in the use of Tritace plus in patients with severe renal impairment (creatinine clearance less than 30 ml / min at 1.73 m2 surface area of the body) and in patients on hemodialysis. Control of the content of electrolytes and the concentration of glucose in the blood serum Treatment with Tritace Plus requires regular monitoring of the content sodium, potassium, calcium, uric acid in the blood serum and glucose in blood. Patients with impaired renal function, with violations of water-electrolyte balance requires more frequent monitoring of potassium in the blood serum.
Other caveats Thiazide diuretics can reduce the concentration in the blood of protein-bound iodine without causing signs of thyroid dysfunction. Thiazide diuretics can cause a temporary and small increase in serum calcium in the absence of known calcium metabolism disorders.Expressed hypercalcemia may indicate latent hyperparathyroidism. Before evaluating parathyroid function, thiazide diuretics should be discarded.
The risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, and simultaneous use of drugs for the treatment of hypokalemia or other drugs that can increase the content potassium in the blood serum (see section "Interaction with other medicinal products ").
Patients should be warned do not use salt substitutes, containing potassium, without preliminary consultation with his own doctor.
It should be borne in mind that with the use of hydrochlorothiazide, positive doping control is possible.