Lorista®
Hypersensitivity reactions
Patients with a history of angioedema (swelling of the face, lips, pharynx/larynx and/or tongue) should be under strict medical supervision when using Lorista® (see section “Side Effects”).
Embryotoxicity
The use of drugs that affect the RAAS during the second and third trimester of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and mortality. The development of oligohydramnios may be associated with fetal pulmonary hypoplasia and skeletal deformities. Possible AEs in newborns include calvarial hypoplasia, anuria, hypotension, renal failure and death. If pregnancy is diagnosed, Lorista® should be discontinued immediately (see section “Use during pregnancy and breastfeeding”).
Arterial hypotension and water-electrolyte imbalance or decreased blood volume
In patients with reduced blood volume (for example, those receiving treatment with large doses of diuretics), symptomatic arterial hypotension may develop. Correction of such conditions must be carried out before using the drug Lorista® or treatment must begin with a lower dose of the drug Lorista® (see section “Method of administration and dosage”).
Fluid and electrolyte imbalance is common in patients with impaired renal function with or without diabetes mellitus, so careful monitoring of these patients is necessary. In clinical trials in patients with type 2 diabetes mellitus with proteinuria, the incidence of hyperkalemia was greater in the losartan group than in the placebo group. Several patients discontinued therapy due to hyperkalemia (see section “Side effects”, subsection “Laboratory and instrumental data”).
During treatment with Lorista®, it is not recommended to take potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes.
Aortic or mitral stenosis, HOCM
Like all drugs that have a vasodilating effect, ARA II should be used with caution in patients with aortic or mitral stenosis or HOCM.
IHD and cerebrovascular diseases
Like all drugs that have a vasodilating effect, ARA II should be used with caution in patients with coronary artery disease or cerebrovascular diseases, since a pronounced decrease in blood pressure in this group of patients can lead to the development of myocardial infarction or stroke.
CHF
As with the use of other drugs that act on the RAAS, patients with CHF and with or without impaired renal function are at risk of developing severe hypotension or acute renal impairment.
Since there is insufficient experience with the use of Lorista® in patients with heart failure and concomitant severe renal impairment, in patients with severe heart failure (NYHA functional class IV), as well as in patients with heart failure and symptomatic life-threatening arrhythmias, the drug Lorista® should be used with caution in patients in these groups.
Primary hyperaldosteronism
Since patients with primary hyperaldosteronism, as a rule, do not have a positive response to therapy with antihypertensive drugs that act by inhibiting the RAAS, the use of Lorista is not recommended in this group of patients.
Liver dysfunction
Data from pharmacokinetic studies indicate that the concentration of losartan in the blood plasma in patients with cirrhosis of the liver is significantly increased, therefore patients with a history of impaired liver function should use the drug Lorista® at a lower dose. There is no experience with the use of losartan in patients with severe liver dysfunction, so Lorista® should not be used in this group of patients (see sections “Pharmacological properties” [subsection “Pharmacokinetics”], “Contraindications”, “Dosage and Administration”).
Renal dysfunction
Due to inhibition of the RAAS, changes in renal function, including the development of renal failure, have been observed in some susceptible patients. These changes in renal function may return to normal after treatment is stopped.
Some drugs that affect the RAAS may increase serum urea and creatinine concentrations in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney. Similar effects have been reported with losartan. Such renal dysfunction may be reversible after discontinuation of therapy. Losartan should be used with caution in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney.
Special patient groups
Ethnic characteristics
Analysis of data from the entire population of patients included in a clinical trial to study the effect of losartan on reducing the incidence of the main composite criterion for evaluating the study in patients with hypertension and left ventricular hypertrophy showed that the ability of losartan, compared with atenolol, to reduce the risk of stroke and myocardial infarction, and also reducing the rate of cardiovascular mortality in patients with hypertension and left ventricular hypertrophy (by 13.0%) does not apply to patients of the Negroid race, although both treatment regimens effectively reduced blood pressure in these patients.
In this study, losartan, compared with atenolol, reduced cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy of all races except blacks. However, in this study, black patients receiving atenolol had a lower risk of the study's primary composite endpoint (i.e., lower combined incidence of cardiovascular death, stroke, and myocardial infarction) compared with race-matched patients receiving losartan.
Children and teenagers
The effectiveness and safety of losartan in children and adolescents under 18 years of age have not been established.
If oliguria or arterial hypotension develops in newborns whose mothers took losartan during pregnancy, symptomatic therapy aimed at maintaining blood pressure and renal perfusion is necessary. Blood transfusions or dialysis may be required to prevent hypotension and/or maintain renal function.
Elderly patients
Clinical studies have not revealed any particularities regarding the safety and effectiveness of losartan in elderly patients (over 65 years of age).
Pharmacological properties of the drug Lorista h/hd
Pharmacodynamics. Losartan is an antihypertensive agent, a selective antagonist of angiotensin II receptors (AT1 type). It binds to AT1 type receptors located in various tissues, including the myocardium, vascular smooth muscle, adrenal cortex and kidneys, blocks the development of the effects of angiotensin II, in particular, reduces arterial vasoconstriction and aldosterone release, wedge pressure in the pulmonary vessels, reduces peripheral vascular resistance, which leads to to a decrease in systemic blood pressure. Losartan does not inhibit the activity of kinase II, an enzyme that catalyzes the breakdown of bradykinin. The maximum effect of losartan is observed 6 hours after taking the drug. This effect lasts for 24 hours, so it is enough to take the drug once a day. The hypotensive effect stabilizes during the first week of treatment, and the maximum hypotensive effect is achieved 3–6 weeks from the start of therapy. Hydrochlorothiazide is a diuretic. Thiazide diuretics inhibit the reabsorption of Na+ and Cl– ions in the distal tubules of the nephrons, increasing the excretion of sodium, potassium, chlorine and water. At the beginning of treatment with hydrochlorothiazide, a decrease in the volume of circulating blood plasma occurs, followed by a decrease in cardiac output and a significant decrease in blood pressure. In response to a decrease in blood pressure and cardiac output, fluid is redistributed from the interstitial space into the intravascular bed, and after 3–4 months there is a gradual normalization of blood plasma volume. With prolonged use of the drug, cardiac output returns to the initial value, and peripheral vascular resistance decreases to a lower level compared to the initial value. Diuresis is usually observed within 2 hours after taking hydrochlorothiazide, reaches a maximum after 3-4 hours and lasts for 6-12 hours. The hypotensive effect appears after 3-4 days of treatment and reaches a maximum after 3-4 weeks. The duration of the hypotensive effect is 12–18 hours. When losartan is combined with hydrochlorothiazide, an additive hypotensive effect is observed, which lasts 24 hours and persists over a long period of treatment. Pharmacokinetics of Losartan. After oral administration, losartan is rapidly absorbed into the gastrointestinal tract. It undergoes significant primary metabolism to form active carboxylic acid metabolites and a number of inactive metabolites. Systemic bioavailability is approximately 33%. The maximum concentration of losartan in the blood serum is achieved within 1 hour, and its active metabolite - within 3-4 hours after administration. 99% of losartan and its active metabolite are bound to plasma proteins, mainly albumin. The clearance of losartan and its active metabolite from blood plasma is about 600 and 50 ml/min, respectively. The renal clearance of losartan and its active metabolite from the kidneys is approximately 75 and 26 ml/min, respectively. When taken orally, about 5% of the dose of losartan taken is excreted in the urine unchanged and 6% in the form of an active metabolite. The half-life is 1.5–2 hours and 6–9 hours, respectively. Approximately 35% is excreted in urine, and approximately 65% in feces. Hydrochlorothiazide. Absorption of hydrochlorothiazide when taken orally is rapid. Its bioavailability is 70%. The maximum concentration in blood plasma is achieved 1.5–5 hours after administration. Approximately 40% of the drug is bound to plasma proteins. About 95% of hydrochlorothiazide is excreted unchanged by the kidneys. Elimination occurs as a result of tubular excretion. The half-life from the body is 5.6–14.8 hours.
Side effects of the drug Lorista h/hd
dizziness, sometimes tachycardia, dry cough, upper respiratory tract infections, diarrhea, edema, abdominal pain, back pain, angioedema, rash, hepatitis, pancreatitis, neutropenia, thrombocytopenia, hypercalcemia and hyperkalemia. Rarely - an increase in the activity of liver enzymes and the level of bilirubin in the blood serum, a decrease in hematocrit and hemoglobin levels is possible; in patients with bilateral renal artery stenosis or with stenosis of the artery of a single kidney, there may be a slight increase in the level of urea and creatinine in the blood serum, but these symptoms do not require cancellation drug.
Drug interactions Lorista h/hd
The drug can be used in combination with other antihypertensive drugs. There were no clinically significant interactions between losartan and digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. With simultaneous use of losartan and rifampicin, the metabolism of losartan and the breakdown of its active metabolites may be accelerated, which leads to a decrease in the effectiveness of losartan. The combined use of losartan and spironolactone, amiloride, triamterene and/or potassium supplements may lead to the development of hyperkalemia. As is the case with other antihypertensive drugs, the severity of the hypotensive effect of losartan may be reduced with simultaneous use of NSAIDs (for example, indomethacin), as well as sympathomimetics. Hydrochlorothiazide reduces lithium excretion. The combined use of losartan with lithium preparations may lead to increased side effects of lithium due to increased reabsorption of lithium in the proximal tubules of nephrons. Therefore, it is recommended to monitor the concentration of lithium in the blood serum and, if possible, avoid the simultaneous use of hydrochlorothiazide and lithium preparations. The combined use of barbiturates, narcotic analgesics (morphine) or consumption of alcoholic beverages may enhance the hypotensive effect of hydrochlorothiazide. In addition, the hypotensive effect of hydrochlorothiazide may also be enhanced by concomitant use of other antihypertensive agents. Hydrochlorothiazide, by weakening the effect of antidiabetic agents, can cause the development of hyperglycemia, therefore, when treating patients with diabetes mellitus, blood glucose levels should be regularly monitored and, if necessary, the dose of the antidiabetic agent should be adjusted. The combined use of hydrochlorothiazide and colestipol or cholestyramine leads to a decrease in the absorption of hydrochlorothiazide by 43 and 85%, respectively. The simultaneous use of hydrochlorothiazide and corticosteroids (including ACTH) may cause the development of hypokalemia. With the combined use of hydrochlorothiazide and pressor amines, the corresponding response to the administration of the latter may be reduced, but this effect is usually insignificant. When performing general anesthesia or administering non-depolarizing muscle relaxants (for example, tubocurarine), the risk of hypotension increases. When taking amiodarone concomitantly with hydrochlorothiazide, the risk of developing arrhythmia due to hypokalemia increases. NSAIDs may reduce the diuretic and hypotensive effects of hydrochlorothiazide. Diflunisal increases the concentration of hydrochlorothiazide in the blood plasma and reduces the severity of its hyperuricemic effect. When the drug is used in combination with digitalis glycosides, the likelihood of toxic effects of cardiac glycosides increases.
Use of the drug Lorista h/hd
The initial and maintenance dose is 1 tablet of Lorista H or Lorista HD 1 time per day. The dose should be adjusted taking into account the degree of blood pressure reduction achieved during 3 weeks of treatment. The maximum recommended dose is 2 Lorista H tablets or 1 Lorista HD tablet per day. For patients with moderately severe renal impairment (creatinine clearance 0.5 ml/s or 30 ml/min), the drug can be prescribed at the usual dose. The drug is not recommended for patients with significant renal impairment, including patients undergoing hemodialysis. The recommended starting dose of losartan for patients with hypovolemia is 25 mg 1 time per day, so treatment with the drug is not recommended until the end of diuretics and elimination of hypovolemia. The drug can be taken both after meals and on an empty stomach. It is recommended to take the drug at the same time of day. If a drug dose is missed, the patient should not double its dose; in this case, he should take the next dose of the drug at the usual time. The duration of treatment is not limited.
Overdose of Lorista h/hd, symptoms and treatment
Data on drug overdose are limited. The most likely consequences of an overdose of losartan may be arterial hypotension and tachycardia; It is also possible to develop bradycardia due to parasympathetic (vagal) stimulation. The main symptoms of hydrochlorothiazide overdose are excessive diuresis, significant hypotension with bradycardia, other cardiac arrhythmias, decreased serum electrolyte levels and impaired core function. In case of overdose, the drug should be discontinued immediately. In case of recent overdose, gastric lavage is recommended. It is necessary to monitor the vital functions of the body and, if necessary, carry out symptomatic treatment. Losartan and its active metabolite are not excreted from the body during hemodialysis.
