TEVA #Circulatory_system #Hypertension #HEALTH_CARE
Pharmacological properties
Pharmacodynamics. Lisinopril and hydrochlorothiazide - an APF inhibitor and a diuretic - have a complementary effect and exhibit an additive antihypertensive effect. ACE catalyzes the conversion of angiotensin i to angiotensin ii, which has a powerful vasoconstrictor effect and stimulates the secretion of aldosterone. The antihypertensive effect of lisinopril is mainly associated with inhibition of the renin-angiotensin-aldosterone system with a decrease in the plasma concentration of angiotensin II and aldosterone. Lisinopril has an antihypertensive effect even in patients with low-grade hypertension. APF is similar to kinase II, an enzyme that degrades bradykinin. It remains unclear whether increased levels of bradykinin (a powerful vasodilator) play a role in the therapeutic effect of lisinopril.
Hydrochlorothiazide is a thiazide diuretic and antihypertensive agent that increases plasma renin levels. Hydrochlorothiazide reduces renal reabsorption of electrolytes in the distal segment of Henle's loop and increases the excretion of sodium, chlorine, potassium, magnesium, bicarbonate and water. Calcium excretion may be reduced. The simultaneous use of lisinopril and hydrochlorothiazide provides a more pronounced hypotensive effect than with the use of these preparations in monotherapy. Lisinopril usually reduces the loss of potassium caused by hydrochlorothiazide.
Pharmacokinetics. Absorption. Lisinopril: about 25%, with interindividual variability of 6-60% at the doses studied (5-80 mg). The presence of food in the gastrointestinal tract does not affect the absorption of lisinopril. Cmax in blood plasma is achieved after 6-8 hours. The effect on blood pressure is noted after 1-2 hours. The maximum effect is achieved after 6 hours and lasts at least 24 hours.
Hydrochlorothiazide: the diuretic effect appears after 2 hours. The maximum effect is achieved after 4 hours. The clinically pronounced effect lasts 6-12 hours.
Distribution. Protein binding: except for ACE, lisinopril does not bind to other blood plasma proteins. For elderly patients, a higher concentration of lisinopril in blood plasma is characteristic due to a decrease in the volume of distribution than in younger patients.
T½. Lisinopril - 12 hours (after several doses). Hydrochlorothiazide - 5.5-15 hours
Metabolism / Elimination. Both active components are excreted unchanged by the kidneys. After oral administration, about 60% of hydrochlorothiazide is excreted within 24 hours.
Indications
Treatment of AR with ineffectiveness of monotherapy with lisinopril or hydrochlorothiazide.
Application
Determination of the effective dose of the preparation depends on the clinical assessment of the patient's condition.
The usual dose is 1 tablet 10 mg / 12.5 mg or 20 mg / 12.5 mg once a day. Lysothiazide should be used at about the same time every day. If the expected therapeutic effect cannot be achieved within 2-4 weeks, the dose can be increased to 2 tablets 1 time per day. In case of insufficient effectiveness of the preparation when administered 1 time per day, it is recommended to divide the daily dose into 2 doses. The maximum daily dose of Lysothiazide is 40 mg / 25 mg. The duration of the course of treatment is determined individually, depending on the severity of the course of the disease.
In patients with creatinine clearance of 30 and 80 ml / min, it is possible to use only Lysothiazide 10 mg + 12.5 mg. To avoid symptomatic hypotension in patients taking diuretics, the diuretic should be discontinued 2-3 days before the appointment of Lysothiazide.
In persons with hepatic impairment, there is no need for dose adjustment.
Taking a fixed combination of lisinopril and hydrochlorothiazide is usually recommended after titrating the doses of the preparation components separately.
In case of clinical need, a direct transition from monotherapy to a fixed combination of lisinopril and hydrochlorothiazide is possible.
Elderly patients. Elderly patients have a high probability of impaired renal function, therefore, if necessary, dose adjustment should be made for this group of patients. Elderly patients should be carefully examined for objective and subjective symptoms of hypertension.
Contraindications
Hypersensitivity to lisinopril and other APF inhibitors, hydrochlorothiazide and sulfonamide derivatives or other components of the preparation. A history of angioedema (including after the use of APF inhibitors, idiopathic and hereditary angioedema). anuria, severe renal dysfunction (creatinine clearance 30 ml / min). severe liver dysfunction. exacerbation of gout. simultaneous use of aliskiren-containing preparations in patients with diabetes mellitus or impaired renal function (glomerular filtration rate 60 ml / min / 1.73 m2). stenosis of the mitral or aortic valve, hypertrophic cardiomyopathy with impaired hemodynamics. primary hyperaldosteronism. renal artery stenosis (bilateral or unilateral). cardiogenic shock. porphyria. state with unstable hemodynamics after acute myocardial infarction. use in patients on hemodialysis using high-flow membranes (eg an69). plasma creatinine level 220 μmol / l. treatment-resistant hypokalemia or hypercalcemia. refractory hyponatremia. during pregnancy or women planning pregnancy (see use during pregnancy and lactation).
Side effects
Side effects due to lisinopril and other APF inhibitors
Blood and lymphatic system disorders: bone marrow suppression, anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia, lymphadenopathy, autoimmune diseases.
Metabolic and nutritional disorders: hypoglycemia, hyperglycemia, hyponatremia.
From the nervous system: dizziness, headache, syncope, paresthesia, taste disturbances, sleep disturbances.
Mental disorders: mood changes, depression, confusion.
From the side of the cardiovascular system: orthostatic effects (including hypotension), in patients with a high risk of myocardial infarction or stroke due to significant arterial hypotension, palpitation, tachycardia, Raynaud's phenomenon, hot flashes.
From the immune system: autoimmune diseases.
On the part of the organ of hearing and balance: vertigo.
From the respiratory system: cough, rhinitis, shortness of breath, bronchospasm, sinusitis, allergic alveolitis / eosinophilic pneumonia.
From the digestive system: diarrhea, nausea, vomiting, abdominal pain, dyspepsia, dry mouth, pancreatitis, intestinal angioedema, constipation, bloating.
Hepatobiliary disorders: increased levels of liver enzymes and bilirubin, hepatocellular or cholestatic hepatitis, jaundice and liver failure *.
Skin and subcutaneous tissue disorders: rash, itching, hypersensitivity / angioedema: angioedema of the face, extremities, lips, tongue, glottis and / or larynx, urticaria, alopecia, psoriasis, increased sweating, pemphigus, toxic epidermal necrolysis, Steve syndrome - Johnson, erythema multiforme, cutaneous pseudolymphoma **.
From the genitourinary system: impaired renal function, uremia, acute renal failure, oliguria / anuria.
From the reproductive system and mammary glands: impotence, gynecomastia.
From the musculoskeletal system: muscle spasms.
From the endocrine system: inadequate secretion of antidiuretic hormone.
General disorders: increased fatigue, asthenia, chest pain.
Laboratory tests: an increase in the level of urea in the blood, an increase in the level of creatinine in the blood plasma, a decrease in hemoglobin, a decrease in the level of hematocrit.
* Reported isolated cases of progression of hepatitis with the development of liver failure. If patients using the fixed combination of lisinopril / hydrochlorothiazide develop jaundice or a significant increase in the level of liver enzymes, stop taking the preparation and switch to alternative treatment.
** Cases of the development of a symptom complex have been reported, which may include one or more of the following reactions: fever, vasculitis, myalgia, arthralgia / arthritis, positive antinuclear antibody (ANA) test, increased ESR, eosinophilia and leukocytosis, rash, photosensitivity or other skin manifestations.
Regarding the safety of preparations containing lisinopril, such adverse reactions have also been reported: imbalance, disorientation, impaired smell, glossitis, fainting, muscle spasms, shortness of breath, upper respiratory tract infections, decreased appetite, constipation, skin flushing, proteinuria.
Side effects due to hydrochlorothiazide
Infections and invasions: sialodenitis.
Blood and lymphatic system disorders: leukopenia, neutropenia / agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, bone marrow suppression.
Metabolic and nutritional disorders: anorexia, hyperglycemia, glucosuria, hyperuricemia, electrolyte imbalance (including hyponatremia, hypokalemia, hypochloremic alkalosis, which can induce hepatic encephalopathy or hepatic coma, hypermagnesemia), increased cholesterol levels, decreased glucose levels, goutinemia , which can lead to the manifestation of latent diabetes mellitus.
Mental disorders: anxiety, depression, sleep disturbance, disorientation, nervousness, mood changes.
From the nervous system: headache, loss of appetite, paresthesia, dizziness, drowsiness.
From the side of the organ of vision: xanthopsia, temporary visual impairment.
On the part of the organ of hearing and balance: vertigo.
From the side of the cardiovascular system: orthostatic hypotension, necrotizing angiitis (vasculitis, cutaneous vasculitis), palpitations, heart rhythm disturbances.
From the respiratory system: respiratory disorders (including pneumonia and pulmonary edema).
From the digestive system: irritation of the gastric mucosa, diarrhea, constipation, pancreatitis, dry mouth, thirst, nausea, vomiting.
Hepatobiliary disorders: jaundice (intrahepatic cholestatic jaundice), cholecystitis.
Skin and subcutaneous tissue disorders: photosensitization, rash, lupus-like reactions, reactivation of skin manifestations of systemic lupus erythematosus, urticaria, anaphylactic reactions, toxic epidermal necrolysis, Stevens-Johnson syndrome.
Musculoskeletal and connective tissue disorders: muscle spasm, muscle weakness, convulsions.
From the genitourinary system: impaired renal function, interstitial nephritis.
On the part of the reproductive system: sexual dysfunction.
General disorders: fever, weakness, pain, shock, exhaustion.
Special instructions
Lisinopril
Symptomatic hypotension has rarely been observed in patients with uncomplicated hypertension. The likelihood of developing arterial hypotension increases in dehydrated patients (for example, as a result of diuretic treatment, restriction of salt intake with food, dialysis, with diarrhea or vomiting), as well as in severe forms of renin-dependent hypertension. In such patients, the level of electrolytes in the blood plasma should be regularly monitored.
Symptomatic arterial hypotension was detected in patients with heart failure, regardless of whether it is combined with renal failure. This is more common in patients with severe heart failure who have to take high-dose loop diuretics and who have been diagnosed with hyponatremia or functional renal failure. Patients with an increased risk of arterial hypotension require careful monitoring during the initial period of treatment and when selecting a dose.
This also applies to patients with coronary artery disease or cerebrovascular disease, in whom a significant decrease in blood pressure can lead to myocardial infarction or cerebrovascular accident (stroke).
If arterial hypotension occurs, the patient should be laid on his back; if necessary, carry out an intravenous infusion of 0.9% sodium chloride solution. A short-term hypotensive reaction is not a contraindication for further doses, which can usually be easily administered after the restoration of the effective blood volume and the disappearance of the fleeting hypotensive reaction.
In some patients with heart failure who have normal or low blood pressure, an additional decrease in systemic blood pressure may occur during treatment with lisinopril. This effect is predictable and, as a rule, does not require discontinuation of lisinopril therapy. If hypotension becomes symptomatic, it may be necessary to reduce the dose or stop taking lisinopril.
In the case of the development of acute myocardial infarction, it is forbidden to use lisinopril if treatment with vasodilators can worsen the patient's hemodynamic status.
In case of persistent arterial hypotension (systolic blood pressure 90 mm Hg for more than 1 hour), treatment with the preparation should be discontinued.
Aortic and mitral valve stenosis / hypertrophic cardiomyopathy. Like other ACE inhibitors, lisinopril should be used with caution in patients with mitral stenosis or obstruction of blood outflow from the left ventricle (with aortic stenosis or hypertrophic cardiomyopathy). If the stenosis is hemodynamically significant, then the use of the preparation is contraindicated (see CONTRAINDICATIONS).
Impaired renal function. In patients with heart failure, arterial hypotension that occurs at the beginning of treatment with ACE inhibitors can lead to a deterioration in renal function. In such cases, the development of ARF has been reported, usually reversible.
In some patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney, ACE inhibitors increase blood urea and plasma creatinine; as a rule, these effects disappear after the preparation is stopped. The likelihood of such events is especially high in patients with renal insufficiency.
The presence of renovascular hypertension increases the risk of severe arterial hypotension and renal failure. Treatment of such patients should be started under the supervision of a physician with low doses and their careful selection. Since diuretics can stimulate the development of the above-described clinical dynamics, during the first weeks of treatment with lisinopril, their intake should be discontinued, and renal function should be closely monitored.
In some patients with hypertension without obvious renal vascular disease, the use of lisinopril, especially while taking diuretics, causes an increase in the level of urea in the blood and creatinine in the blood plasma; these changes are usually minor and transient. The likelihood of their occurrence is higher in patients with impaired renal function. In such cases, it may be necessary to reduce the dose and / or stop taking diuretics and / or lisinopril.
In the case of renal artery stenosis (in particular, in the case of bilateral stenosis or stenosis of an artery of a single kidney), taking the preparation can cause or increase renal dysfunction, which can lead to the development of ARF.
Previous diuretic use. Diuretics should be discontinued 2-3 days before starting treatment with lisinopril / hydrochlorothiazide. If this is not possible, treatment should be started with lisinopril monotherapy at a dose of 5 mg.
Patients after kidney transplantation. Since there is no experience with the use of lisinopril in patients who have undergone kidney transplantation, it is not recommended to prescribe lisinopril to such patients.
Hypersensitivity / angioedema. In rare cases, angioedema of the face, extremities, lips, tongue, glottis and larynx has been reported in patients taking ACE inhibitors, including lisinopril. Angioedema can develop at any time during treatment. In such cases, lisinopril should be discontinued immediately, appropriate treatment should be carried out and the patient's health should be monitored. Even in cases where the edema is limited only by the tongue and there are no signs of respiratory failure, the patient's condition should be monitored, since treatment with antihistamines and corticosteroids may not be sufficient.
Recorded isolated deaths due to angioedema of the larynx or tongue. If swelling spreads to the tongue, glottis, or larynx, breathing problems may develop, especially in patients who have had previous airway surgery. In such cases, urgent measures should be taken immediately, which, in particular, may include the introduction of epinephrine and / or the provision of an airway. The patient should be under medical supervision until the symptoms disappear completely and sustainably.
In patients with a history of angioedema not associated with the use of an ACE inhibitor, the risk of developing angioedema in response to the use of preparations of this group may be increased.
Anaphylactoid reactions during hemodialysis. Anaphylactic reactions have been reported in patients who underwent hemodialysis using high-flow membranes (eg AN69) and concomitantly taking ACE inhibitors. These patients should be offered to change the dialysis membrane to a different type of membrane or to use a different class of antihypertensive preparation.
Anaphylactoid reactions in LDL apheresis. Rarely, during LDL apheresis with dextran sulfate, patients receiving ACE inhibitors can develop life-threatening anaphylactic reactions. Such reactions can be avoided by temporarily discontinuing therapy with an ACE inhibitor before each apheresis.
Desensitization. Persistent anaphylactoid reactions develop in patients taking ACE inhibitors during desensitization therapy (for example, to Hymenoptera venom). These reactions were avoided in the same patients by temporary discontinuation of ACE inhibitors, but after careless repeated use of the preparation, the reactions resumed.
Liver failure. Very rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice, progresses rapidly to necrosis, and is sometimes fatal. The mechanism of this syndrome has not been identified. Patients who develop jaundice or have significantly increased levels of liver enzymes while taking lisinopril should stop taking the preparation and provide appropriate medical care.
Neutropenia / agranulocytosis. Cases of neutropenia / agranulocytosis, thrombocytopenia and anemia have been reported in patients treated with ACE inhibitors. In patients with normal renal function and no other complicating factors, neutropenia is rare. After discontinuation of an ACE inhibitor, neutropenia and agranulocytosis are reversible. With extreme caution, lisinopril is prescribed to patients with collagenosis, to patients undergoing treatment with immunosuppressants, taking allopurinol or procainamide, and also when these factors are combined, especially against the background of existing renal dysfunction. Some of these patients develop severe infections that do not always respond to intensive antibiotic therapy. When using the preparation in such patients, it is recommended to periodically monitor the number of leukocytes in the blood and warn the patient about the need to report any signs of infection.
Racial affiliation. ACE inhibitors can cause more pronounced angioedema in black patients than in Caucasian patients. Also, in this group of patients, the hypotensive effect of lisinopril is less pronounced due to the predominance of low fractions of renin.
Lithium. In general, the combination of lithium and lisinopril is not recommended.
Cough. With the use of ACE inhibitors, an unproductive persistent cough may appear, which disappears after stopping treatment. Cough caused by the use of ACE inhibitors should be considered in the differential diagnosis of cough as one of the possible options.
Surgery / Anesthesia. In patients undergoing surgery or anesthesia with preparations that lower blood pressure, lisinopril can block the increase in the formation of angiotensin II under the influence of compensatory release of renin. If arterial hypotension resulting from this mechanism is detected, it is necessary to adjust the BCC level.
Hyperkalemia. In some patients taking ACE inhibitors, including lisinopril, an increase in the level of potassium in the blood plasma is noted. The risk group for developing hyperkalemia includes patients with renal failure or diabetes mellitus, people taking potassium-sparing diuretics, dietary supplements with potassium or potassium-containing salts, and patients taking other preparations that increase the level of potassium in the blood plasma (heparin). If the intake of the above preparations during treatment with ACE inhibitors is necessary, regular monitoring of the level of potassium in the blood plasma is recommended.
Patients with diabetes mellitus. In diabetic patients taking oral antidiabetic agents or insulin, it is necessary to carefully monitor the blood glucose level within 1 month of therapy with ACE inhibitors.
Hydrochlorothiazide
Impaired renal function. In patients with kidney disease, thiazides can cause azotemia. In persons with impaired renal function, the cumulative effect of preparations is possible. With progressive kidney disease, characterized by an increase in the level of non-protein nitrogen, the advisability of continuing therapy should be carefully evaluated and the possibility of discontinuing diuretic therapy should be considered.
Liver dysfunction. Thiazides should be used with caution in patients with impaired liver function or progressive liver disease, since the slightest disturbance in the water and electrolyte balance in these patients can lead to the development of hepatic coma.
Metabolic and endocrine effects. Thiazide diuretic therapy can reduce glucose tolerance. Therefore, in patients with diabetes mellitus, it may be necessary to adjust the dose of insulin or oral antidiabetic (hypoglycemic) preparations. Latent diabetes mellitus may manifest during thiazide therapy.
An increase in cholesterol and triglycerides may be associated with thiazide diuretic therapy. Some patients taking thiazide diuretics may develop hyperuricemia or present with gout.
Electrolyte imbalance. As with any diuretic treatment, patients need to periodically measure their blood plasma electrolyte levels. Thiazides, including hydrochlorothiazide, can lead to water-electrolyte imbalance (hypokalemia, hyponatremia, and hypochloremic alkalosis). Symptoms of fluid-electrolyte imbalance are dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscle weakness, hypotension, oliguria, tachycardia, and gastrointestinal disorders such as nausea and vomiting.
Although hypokalemia may develop with the use of thiazide diuretics, concomitant use with lisinopril can reduce diuretic-induced hypokalemia. Groups at high risk of developing hypokalemia include patients with cirrhosis of the liver, increased urine output, insufficient oral replacement for electrolyte loss, as well as those receiving corticosteroid or ACTH therapy.
In hot weather, patients prone to edema may experience hyponatremia. Chloride deficiency is usually mild and does not require treatment.
Thiazides can reduce urinary calcium excretion and cause a slight intermittent increase in plasma calcium levels even in the absence of severe disorders of calcium metabolism. Significant hypercalcemia can be a sign of latent hyperparathyroidism, therefore it is recommended to stop taking thiazide diuretics before examining the function of the parathyroid glands. Thiazides can increase renal excretion of magnesium, which can lead to hypomagnesemia.
Doping test. Hydrochlorothiazide can cause a positive doping test.
Other. Hypersensitivity reactions may occur in patients with or without a history of allergic or asthma. Cases of exacerbation or reactivation of systemic lupus erythematosus have been reported.
Laboratory indicators. The preparation can affect the results of such laboratory tests: hydrochlorothiazide can reduce the level of protein-bound iodine in the blood plasma (treatment with hydrochlorothiazide should be discontinued before laboratory tests to assess the function of the parathyroid glands) and increase the concentration of free bilirubin in the blood plasma.
Lisinopril / hydrochlorothiazide
Arterial hypotension and water-electrolyte imbalance. In some cases, symptomatic hypotension may occur after taking the first dose of lisinopril / hydrochlorothiazide. The risk of developing symptomatic hypotension in hypertensive patients is increased in the presence of water-electrolyte imbalance (eg, hypovolemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia), which can be caused by diuretic therapy, a diet with low sodium intake, dialysis, or recurrent diarrhea or vomiting. In such patients, the level of electrolytes in the blood plasma should be monitored on a regular basis.
The initiation of therapy and dose adjustment for patients who are at increased risk of developing symptomatic hypotension should be carried out with extreme caution.
Treatment of patients with coronary artery disease or cerebrovascular accident should be carried out with extreme caution, since an excessive decrease in blood pressure can cause myocardial infarction or stroke.
In the event of acute arterial hypotension, the patient must be laid on his back; if necessary, carry out an intravenous infusion of 0.9% sodium chloride solution. A transient hypotensive reaction is not a contraindication for further administration of the preparation. After the restoration of normal blood pressure and effective blood volume, the preparation can be continued at a lower dose, or treatment can be continued with one of the two components.
As with other vasodilators, lisinopril / hydrochlorothiazide should be used with caution in patients with aortic stenosis or hypertrophic cardiomyopathy.
Impaired renal function. Thiazides are ineffective in patients with a creatinine clearance of 30 ml / min (i.e., with moderate to severe renal impairment).
Lisinopril / hydrochlorothiazide can be prescribed to patients with creatinine clearance of 30–80 ml / min only after titration of doses of individual components has shown that there is a need for a combination preparation.
In some patients without significant renovascular disorders, a slight and temporary increase in blood urea and plasma creatinine levels was noted when lisinopril was used simultaneously with a diuretic. If such a reaction develops while using lisinopril / hydrochlorothiazide, therapy should be discontinued. Under appropriate conditions, resumption of treatment is possible at lower doses, and one of the components can be used in monotherapy.
Risk of hypokalemia. When an ACE inhibitor is combined with a thiazide diuretic, hypokalemia may develop. Therefore, you should regularly monitor the level of potassium in the blood.
Neutropenia / agranulocytosis. The use of a fixed combination of lisinopril and hydrochlorothiazide should be discontinued if neutropenia is detected or suspected (neutrophil count 1000 / mm3).
Double blockade of the RAAS. It was reported that the simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of arterial hypotension, hyperglycemia, renal dysfunction (including ARF). Thus, double blockade of RAAS by the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended.
If it is necessary to use dual blockade therapy, it should be carried out under the supervision of a specialist and regularly monitor kidney function, electrolyte levels and blood pressure. Patients with diabetic nephropathy are not recommended to simultaneously use ACE inhibitors and angiotensin II receptor blockers.
Application during pregnancy or lactation. Pregnancy. The preparation should not be used in women who are planning a pregnancy. If pregnancy is confirmed by a preparation during treatment, its use should be discontinued immediately and, if necessary, replaced with another preparation approved for use in pregnant women.
Lactation
ACE inhibitors. Since there are no data on the use of lisinopril / hydrochlorothiazide during breastfeeding, lisinopril / hydrochlorothiazide is not recommended, preference should be given to alternative agents with a known safety profile, especially in the case of feeding a newborn or premature baby.
Hydrochlorothiazide. Hydrochlorothiazide is excreted in breast milk in small amounts. High doses of thiazides that cause intense diuresis can suppress milk production. It is not recommended to use lisinopril / hydrochlorothiazide during breastfeeding. If lisinopril / hydrochlorothiazide is used during breastfeeding, its dose should be as low as possible.
Thus, the preparation is contraindicated for use during lactation.
Children. The safety and efficacy of the lisinopril / hydrochlorothiazide combination in children has not been established, therefore, a preparation in this age category should not be prescribed.
The ability to influence the reaction rate when driving or operating machinery. It should be borne in mind that while taking lisinopril, the ability to drive vehicles or work with potentially dangerous mechanisms may be impaired due to possible dizziness and fatigue.
Interactions
Double blockade of raas. It has been demonstrated that double blockade of raas with the simultaneous use of APF inhibitors, angiotensin II receptor antagonists or aliskiren is characterized by a higher incidence of adverse reactions such as arterial hypotension, hyperglycemia, impaired renal function (including opn), compared with the use of monotherapy.
Lisinopril
Diuretics At the beginning of the use of a combination of lisinopril with diuretics, patients may periodically experience an excessive decrease in blood pressure. The risk of developing symptomatic arterial hypotension with the use of lisinopril can be reduced if diuretic treatment is discontinued before starting lisinopril therapy.
NSAIDs, including acetylsalicylic acid ≥3 g / day. Long-term use of NSAIDs can reduce the severity of the antihypertensive effect of ACE inhibitors, cause an increase in plasma potassium levels, and impair renal function. These effects are usually reversible. Rarely, ARF can develop, especially in at-risk patients such as the elderly and dehydrated patients.
Other antihypertensive preparations. The simultaneous use of these preparations can increase the hypotensive effect of lisinopril. Concomitant use with nitroglycerin and other nitrates or other vasodilators can further lower blood pressure.
Tricyclic antidepressants / antipsychotics / anesthetics. The combined use of certain anesthetics, tricyclic antidepressants and antipsychotics with ACE inhibitors can further lead to a decrease in blood pressure.
Sympathomimetic preparations. Sympathomimetic preparations can reduce the severity of the antihypertensive effect of ACE inhibitors.
Antidiabetic preparations. The simultaneous use of ACE inhibitors and antidiabetic preparations(insulin, hypoglycemic preparations) can enhance the effect of lowering blood glucose with the risk of hypoglycemia (usually during the first weeks of combination therapy and in patients with renal failure).
Acetylsalicylic acid, thrombolytic preparations, β-adrenergic receptor blockers, nitrates. Lisinopril can be used simultaneously with acetylsalicylic acid (in cardiac doses), thrombolytic preparations, β-adrenergic receptor blockers and / or nitrates.
Allopurinol. With the simultaneous use of ACE inhibitors with allopurinol, the risk of developing renal failure increases and there may be an increased risk of developing leukopenia.
Cyclosporine. The simultaneous use of ACE inhibitors and cyclosporine increases the risk of developing renal failure and hyperkalemia.
Lovastatin. The simultaneous use of ACE inhibitors and lovastatin increases the risk of developing hyperkalemia.
Procainamide, cytostatics or immunosuppressive preparations . The simultaneous use of these preparations with ACE inhibitors can lead to an increased risk of developing leukopenia.
Hemodialysis. Lisinopril / hydrochlorothiazide is not indicated for patients requiring dialysis, since a high incidence of anaphylactoid reactions has been recorded in individuals who have been on dialysis using high-flow membranes (for example AN69) simultaneously with the use of ACE inhibitors.
Gold. Nitritoid reactions (symptoms of vasodilation, including hot flashes, nausea, dizziness, arterial hypotension, which can be very severe) after an injection of a gold preparation (for example sodium aurothiomalate) were observed more often in patients treated with ACE inhibitors.
Lithium. The combination of lithium and lisinopril is not recommended.
Hydrochlorothiazide
Amphotericin B (for parenteral use), carbenoxolone, corticosteroids, corticotropin (ACTH), or stimulant laxatives. Combined use with hydrochlorothiazide can cause electrolyte imbalances, in particular hypokalemia.
Calcium salts. Against the background of combined use with thiazide diuretics, an increase in the plasma level of calcium may occur as a result of a decrease in its excretion.
Cardiac glycosides. Increased risk of intoxication with digitalis preparations against the background of hypokalemia induced by thiazide diuretics.
Resins of cholestyramine and colestipol. Concomitant use with hydrochlorothiazide can reduce or slow down the absorption of hydrochlorothiazide. Thus, sulfa diuretics should be taken at least 1 hour before or 4–6 hours after taking these preparations.
Non-depolarizing muscle relaxants (tubocurarine chloride). The effect of these preparations may be enhanced by hydrochlorothiazide.
Preparations that cause paroxysmal ventricular tachycardia as a pirouette. Due to the risk of hypokalemia, special care should be taken when using hydrochlorothiazide concomitantly with preparations that are associated with pirouette-type paroxysmal ventricular tachycardia, such as some antipsychotic preparations and other preparations.
Sotalol. Hypokalemia caused by thiazide diuretics may increase the risk of sotalol-induced arrhythmias.
NSAIDs. Concomitant use with hydrochlorothiazide can weaken the hypotensive effect of thiazide diuretics.
Ethanol / preparations of the barbiturates group / narcotic analgesics. Orthostatic hypotension is possible.
Antidiabetic medicines (oral medicines and insulins). Dose adjustment of antidiabetic preparations may be required.
Medicines for gout. Dose adjustment of medications for gout may be required because hydrochlorothiazide may increase plasma uric acid levels. Increasing the dose of probenecid or sulfinpyrazone may be required. With the combined use of thiazide diuretics, the number of cases of hypersensitivity reactions to allopurinol may increase.
Hydrochlorothiazide can reduce plasma levels of iodine bound to proteins.
Immunosuppressants, cytostatics. Concomitant use can increase the risk of leukopenia.
Hydrochlorothiazide may cause false results on the benthromide test.
Lisinopril / hydrochlorothiazide
Potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes. The use of potassium-containing dietary supplements, potassium-sparing diuretics, or potassium-containing salt substitutes can lead to significant increases in plasma potassium levels, especially in patients with impaired renal function. While taking lisinopril against the background of potassium-excreting diuretics, hypokalemia caused by their intake may be weakened.
Trimethoprim. The simultaneous use of ACE inhibitors and thiazide diuretics with trimethoprim increases the risk of hyperkalemia.
Periodic monitoring of the level of potassium in the blood plasma and ECG examination are recommended if hydrochlorothiazide is taken simultaneously with preparations that cause polymorphic tachycardia of the pirouette type (ventricular tachycardia) (including some antiarrhythmic preparations), since hypokalemia is a factor contributing to the development of pirouette tachycardia:
class Ia antiarrhythmics (eg quinidine, hydroquinidine, disopyramide); class III antiarrhythmics (eg amiodarone, sotalol, dofetilide, ibutilide); some antipsychotics (for example, thioridazine, chlorpromazine, levomepromazine, trifluorperazine, cyamemazine, sulpiride, sultopride, amisulpiride, tiapride, pimozide, haloperidol, droperidol); other preparations (for example, bepridil, cisapride, diphemanil, erythromycin for IV administration, halofantrine, mizolastine, pentamidine, terfenadine, vincamine for IV administration).
Influence on the results of laboratory tests. Due to the effect on calcium metabolism, thiazides can affect the results of assessing the function of the parathyroid glands (see SPECIAL INSTRUCTIONS).
Carbamazepine. Given the risk of symptomatic hyponatremia, clinical and biological monitoring is necessary.
Iodine contrast media. In the case of diuretic-induced dehydration, the risk of developing acute renal failure increases, mainly with the use of high doses of iodine-containing contrast media. Patients require rehydration prior to administering iodine-containing medications.
Amantadine. Thiazides, including hydrochlorothiazide, may increase the risk of side effects of amantadine.
Overdose
Symptoms associated with an overdose of APF inhibitors: arterial hypotension, circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, increased heart rate, bradycardia, dizziness, anxiety, cough.
For treatment in case of overdose, it is recommended to intravenously administer a physiological solution. In case of arterial hypotension, the patient should be given a "shock" position (on the back with raised legs). Perhaps the introduction of an infusion of angiotensin II and / or intravenous administration of catecholamines. If the preparation has been recently taken, measures should be taken to eliminate lisinopril (stimulation of vomiting, gastric lavage, administration of adsorbents and sodium sulfate). Lisinopril can be removed from the body by hemodialysis. Therapy with cardiac stimulants is indicated in the case of bradycardia that is resistant to treatment with other therapeutic agents. The main indicators of the state of the body, the electrolyte balance of blood plasma and the concentration of creatinine are subject to constant monitoring.
Symptoms due to an overdose of hydrochlorothiazide: excessive diuresis, depression of consciousness (including coma), convulsions, paresis, arrhythmia, renal failure.
Cardiovascular symptoms: tachycardia, arterial hypotension, shock.
Neurological symptoms: weakness, confusion, dizziness, muscle spasms, paresthesias, exhaustion, impaired consciousness.
Gastrointestinal symptoms: nausea, vomiting, thirst.
Renal symptoms: polyuria, oliguria, anuria.
Deviation of laboratory parameters: hypokalemia, hyponatremia, hypochloremia, alkalosis, increased level of urea nitrogen in the blood.
Bradycardia or vagal reactions can be treated with atropine. In the case of concomitant use of digitalis preparations, hypokalemia may develop, which increases the risk of arrhythmia.
Storage conditions
At a temperature not higher than 30 ° C.
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