Instructions for use LORTENZA®
The antihypertensive effect of Lortenza may be enhanced when used simultaneously with other antihypertensive drugs. Therefore, the simultaneous use of various antihypertensive drugs should be justified.
Amlodipine
The simultaneous use of amlodipine with thiazide diuretics, alpha-blockers or ACE inhibitors is considered safe.
Unlike other BMCCs, no clinically significant interaction with amlodipine (III generation BMCCs) was detected when used simultaneously with NSAIDs, incl. and with indomethacin.
It is possible to enhance the antihypertensive effect of BMCC when used simultaneously with thiazide and loop diuretics, ACE inhibitors and nitrates, as well as when used simultaneously with alpha1-blockers and antipsychotics.
Concomitant use of amlodipine with inhibitors of the CYP3A4 isoenzyme requires careful monitoring of symptoms of arterial hypotension and peripheral edema. With simultaneous use of diltiazem at a dose of 180 mg/day and amlodipine at a dose of 5 mg/day in elderly patients, the systemic exposure of amlodipine increases by 60%. Erythromycin, when used simultaneously, increases the Cmax of amlodipine in blood plasma in young patients by 22%, and in elderly patients by 50%. At the same time, strong inhibitors of the CYP3A4 isoenzyme (ketoconazole, itraconazole, ritonavir) can increase the concentration of amlodipine in the blood plasma to an even greater extent.
Despite the fact that an accurate quantitative assessment of the interaction between amlodipine and inducers of the CYP3A4 isoenzyme (for example, rifampicin, St. John's wort) has not been obtained, regular monitoring of blood pressure is recommended during their simultaneous use.
Beta-blockers, when used simultaneously with amlodipine, can cause an exacerbation of CHF.
Although negative inotropic effects have generally not been observed in amlodipine studies, some CBMCs may enhance the negative inotropic effects of antiarrhythmic drugs that prolong the QT interval (eg, amiodarone and quinidine).
A single dose of sildenafil in a dose of 100 mg in patients with arterial hypertension does not affect the pharmacokinetic parameters of amlodipine.
Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.
Ethanol (beverages containing alcohol):
- amlodipine with single and repeated use at a dose of 10 mg does not affect the pharmacokinetics of ethanol.
Neuroleptics and isoflurane enhance the antihypertensive effect of dihydropyridine derivatives.
With intravenous administration of dantrolene during therapy with amlodipine, collapse, arrhythmias, decreased strength of heart contractions and hyperkalemia are possible.
Calcium supplements may reduce the antihypertensive effect of BMCC.
With the simultaneous use of amlodipine with lithium preparations, an increase in the manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus) is possible.
Amlodipine does not change the pharmacokinetics of cyclosporine.
It has no effect on the serum concentration of digoxin and its renal clearance.
Does not significantly affect the effect of warfarin (prothrombin time).
Cimetidine does not affect the pharmacokinetics of amlodipine.
In in vitro studies, amlodipine does not affect the plasma protein binding of digoxin, phenytoin, warfarin and indomethacin.
A simultaneous single dose of 240 ml of grapefruit juice and amlodipine orally at a dose of 10 mg is not accompanied by a significant change in the pharmacokinetics of amlodipine.
A single dose of aluminum or magnesium-containing antacids does not have a significant effect on the pharmacokinetics of amlodipine.
Losartan
As with the use of other drugs that block the formation of angiotensin II and its effects, the simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride, eplerenone), potassium supplements and potassium-containing salt substitutes may lead to an increase in serum potassium.
As with the use of other drugs that affect sodium excretion, losartan may reduce lithium excretion; therefore, when using lithium preparations and angiotensin II receptor antagonists simultaneously, it is necessary to carefully monitor the concentration of lithium in the blood serum.
In some patients with impaired renal function who have been treated with NSAIDs, including selective COX-2 inhibitors, concomitant use of ACE inhibitors and/or angiotensin II receptor antagonists, including losartan, may cause a further deterioration of renal function, including the development of acute renal failure. Usually this effect is reversible. NSAIDs, including selective COX-2 inhibitors, may reduce the effect of angiotensin II receptor antagonists, including losartan. Therefore, the antihypertensive effect of angiotensin II receptor antagonists may be weakened by simultaneous use of NSAIDs, in particular selective COX-2 inhibitors. Thus, simultaneous use of the amlodipine/losartan combination with NSAIDs should be used with caution in patients with impaired renal function.
Dual blockade of the RAAS (simultaneous use of ACE inhibitors and angiotensin II receptor antagonists) in patients with atherosclerosis, CHF or diabetes mellitus with target organ damage is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) in comparison with the use of a drug from one of the listed groups. Double blockade of the RAAS is possible only in selected cases under careful monitoring of renal function.
The simultaneous use of losartan with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (creatinine clearance less than 60 ml/min) and is not recommended in other patients.
There were no pharmacokinetically significant interactions between losartan and drugs such as hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital. Taking rifampicin, an inducer of drug metabolism, reduces the concentrations of losartan and its active metabolite in the blood plasma.
In clinical studies, the use of two inhibitors of the CYP3A4 isoenzyme was studied. Ketoconazole did not affect the metabolism of losartan to the active metabolite after intravenous administration of losartan. Erythromycin did not have a clinically significant effect on the pharmacokinetics of losartan when administered orally.
Fluconazole, a CYP2C9 inhibitor, reduces the concentration of the active metabolite of losartan and increases the concentration of losartan in the blood plasma, but the pharmacodynamic significance of the simultaneous use of losartan and CYP2C9 inhibitors has not been established. It has been shown that patients whose body does not convert losartan into the active metabolite have a very rare and specific defect in the CYP2C9 isoenzyme. These data indicate that the metabolism of losartan to its active metabolite is mediated primarily by CYP2C9 rather than by CYP3A4.
Lortenza, 30 pcs., 10 mg+100 mg, film-coated tablets
The antihypertensive effect of Lortenza may be enhanced when used concomitantly with other antihypertensive agents. Therefore, the simultaneous use of various antihypertensive drugs should be justified.
Amlodipine
The simultaneous use of amlodipine with thiazide diuretics, alpha-blockers or ACE inhibitors is considered safe.
Unlike other CCBs, no clinically significant interaction with amlodipine (III generation CCB) was detected when used simultaneously with NSAIDs, incl. and indomethacin.
It is possible to enhance the antihypertensive effect of CCBs when used simultaneously with thiazide and loop diuretics, ACE inhibitors and nitrates, as well as when used simultaneously with alpha1-blockers and antipsychotics.
Concomitant use of amlodipine with inhibitors of the CYP3A4 isoenzyme requires careful monitoring of symptoms of arterial hypotension and peripheral edema. With simultaneous use of diltiazem at a dose of 180 mg/day and amlodipine at a dose of 5 mg/day in elderly patients, the systemic exposure of amlodipine increases by 60%.
Erythromycin, when used simultaneously, increases the Cmax of amlodipine in blood plasma in young patients by 22%, and in elderly patients by 50%. At the same time, strong inhibitors of the CYP3A4 isoenzyme (ketoconazole, itraconazole, ritonavir) can increase the concentration of amlodipine in the blood plasma to an even greater extent.
Despite the fact that an accurate quantitative assessment of the interaction between amlodipine and inducers of the CYP3A4 isoenzyme (for example, rifampicin, St. John's wort) has not been obtained, regular monitoring of blood pressure is recommended against the background of their simultaneous use.
Beta-blockers, when used simultaneously with amlodipine, can cause an exacerbation of CHF.
Although negative inotropic effects are not typically observed in amlodipine studies, some CCBs may enhance the negative inotropic effects of antiarrhythmic drugs that cause QT prolongation (eg, amiodarone and quinidine).
A single dose of 100 mg of sildenafil in patients with hypertension does not affect the pharmacokinetic parameters of amlodipine.
Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.
Ethanol (drinks containing alcohol): amlodipine with single and repeated use in a dose of 10 mg does not affect the pharmacokinetics of ethanol.
Neuroleptics and isoflurane enhance the antihypertensive effect of dihydropyridine derivatives.
With intravenous administration of dantrolene during therapy with amlodipine, collapse, arrhythmias, decreased strength of heart contractions and hyperkalemia are possible.
Calcium supplements may reduce the antihypertensive effect of CCBs.
With the simultaneous use of amlodipine with lithium preparations, an increase in the manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus) is possible.
Amlodipine does not change the pharmacokinetics of cyclosporine.
Does not affect the serum concentration of digoxin and its renal clearance.
Does not have a significant effect on the action of warfarin (WW).
Cimetidine does not affect the pharmacokinetics of amlodipine.
in vitro studies
amlodipine does not affect the binding of digoxin, phenytoin, warfarin and indomethacin to plasma proteins.
A simultaneous single dose of 240 mg of grapefruit juice and 10 mg of amlodipine orally is not accompanied by a significant change in the pharmacokinetics of amlodipine.
A single dose of aluminum or magnesium-containing antacids does not have a significant effect on the pharmacokinetics of amlodipine.
Losartan
As with the use of other drugs that block the formation of angiotensin II and its effects, the simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride, eplerenone), potassium supplements and potassium-containing salt substitutes may lead to an increase in serum potassium levels. As with the use of other drugs that affect sodium excretion, losartan can reduce the excretion of lithium, therefore, when using lithium preparations and ARA II simultaneously, it is necessary to carefully monitor the concentration of lithium in the blood serum.
In some patients with impaired renal function who have been treated with NSAIDs, including selective COX-2 inhibitors, concomitant use of ACE inhibitors and/or ARB II, including losartan, may cause a further deterioration of renal function, leading to the development of acute renal failure (ARF). Usually this effect is reversible. NSAIDs, including selective COX-2 inhibitors, may reduce the effect of ARB II, including losartan. Therefore, the antihypertensive effect of ARA II may be weakened by simultaneous use of NSAIDs, in particular selective COX-2 inhibitors. Thus, the simultaneous use of amlodipine/losartan with NSAIDs should be used with caution in patients with impaired renal function.
Double blockade of the RAAS (simultaneous use of ACE inhibitors and ARB II) in patients with atherosclerosis, CHF or diabetes mellitus with target organ damage is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) compared with the use of a drug from one of the listed groups. Double blockade of the RAAS is possible only in selected cases with careful monitoring of renal function.
Concomitant use of losartan with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (creatinine clearance less than 60 ml/min) and is not recommended in other patients.
There were no pharmacokinetically significant interactions between losartan and drugs such as hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital.
Taking rifampicin, an inducer of drug metabolism, reduces the concentrations of losartan and its active metabolite in the blood plasma.
In clinical studies, the use of two inhibitors of the CYP3A4 isoenzyme was studied. Ketoconazole did not affect the metabolism of losartan to the active metabolite after intravenous administration of losartan.
Erythromycin did not have a clinically significant effect on the pharmacokinetics of losartan when administered orally.
Fluconazole, an inhibitor of the CYP2C9 isoenzyme, reduces the concentration of the active metabolite of losartan and increases the concentration of losartan in the blood plasma, but the pharmacodynamic significance of the simultaneous use of losartan and inhibitors of the CYP2C9 isoenzyme has not been established. It has been shown that patients who do not metabolize losartan into the active metabolite have a very rare and specific defect in the CYP2C9 isoenzyme. These data indicate that the metabolism of losartan to its active metabolite is mediated primarily by CYP2C9 rather than by CYP3A4.
Lortenza®
Patients with reduced blood volume or severe aortic stenosis
In patients with reduced blood volume (for example, when taking high doses of diuretics, severe diarrhea, vomiting and other conditions leading to hypovolemia) or with severe aortic stenosis, symptomatic arterial hypotension may develop at the beginning of therapy with Lortenza®. Correction of such conditions should be carried out before starting therapy or treatment should be started with a lower dose of Lortenza®. For patients whose daily dose of losartan is 25 mg, the use of Lortenza® is not recommended (see section "Dosage and Administration").
Special instructions and precautions related to amlodipine
Due to the prolonged T1/2, vasodilation that develops as a result of taking amlodipine may persist even after its discontinuation. Thus, the use of another vasodilator after discontinuation of amlodipine should be done with caution, individual assessment of the dose, dosing interval and active monitoring of the patient's condition are necessary.
During the treatment period, it is necessary to control body weight and salt intake, and prescribe an appropriate diet. It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gum hyperplasia).
Unstable angina and myocardial infarction
After initiating therapy or increasing the dose of amlodipine, unstable angina and acute myocardial infarction may develop, especially in patients with severe HOCM.
Special instructions and precautions related to losartan
Hyperkalemia (plasma potassium content > 5.5 mmol/l) was observed in 1.5% of patients taking losartan as monotherapy. In none of these cases did the drug need to be discontinued. The simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride, eplerenone), potassium supplements, potassium-containing salt substitutes, as well as drugs that can lead to increased potassium levels in the blood plasma (for example, heparin) with losartan should be justified ( especially in elderly patients with impaired renal function), and the potassium content in the blood plasma should be monitored.
While taking losartan, patients should not take potassium supplements or table salt substitutes containing potassium without first consulting their doctor.
Taking losartan can lead to transient arterial hypotension, accompanied by shock, fainting and shortness of breath.
Lortenza® should be used with caution in patients:
— with reduced BCC;
- on a diet with limited salt.
Hypersensitivity reactions
In patients with a history of angioedema (swelling of the larynx, vocal cords, face, lips, pharynx and/or tongue), the use of Lortenza® should be carefully monitored (see section "Side effects").
Embryotoxicity
The use of drugs that affect the RAAS in the II-III trimesters of pregnancy reduces fetal renal function and increases the incidence of morbidity and mortality in the fetus and newborn. The development of oligohydramnios may be associated with fetal lung hypoplasia and skeletal deformation. Possible adverse events in neonates include calvarial hypoplasia, anuria, hypotension, renal failure and death. If pregnancy is diagnosed, Lortenza® should be discontinued immediately (see section “Use during pregnancy and breastfeeding”).
Water-electrolyte imbalance
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. Laboratory and instrumental data”).
Aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy
Like all drugs that have a vasodilating effect, ARA II should be used with caution in patients with aortic or mitral stenosis, or HOCM.
Chronic heart failure
As with the use of other drugs that act on the RAAS, in patients with CHF and with or without impaired renal function, there is a risk of developing severe arterial hypotension or acute renal impairment.
Since there is insufficient experience with the use of losartan in patients with CHF and concomitant severe renal impairment, in patients with severe heart failure (NYHA functional class III-IV), as well as in patients with heart failure and symptomatic life-threatening arrhythmias, Lortenza ® should be used with caution.
In patients with CHF of functional class III-IV (according to the NYHA classification) of non-ischemic origin, an increased incidence of pulmonary edema was observed during the use of amlodipine, despite the absence of signs of worsening heart failure.
Coronary heart disease 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.
Primary hyperaldosteronism
Since patients with primary hyperaldosteronism generally do not respond well to antihypertensive drugs that act by inhibiting the RAAS, the use of Lortenza is not recommended in this group of patients.
Patients with liver failure
Data from pharmacokinetic studies indicate that patients with liver cirrhosis experience a significant increase in plasma concentrations of losartan. Lortenza should not be used in patients with severe hepatic impairment (Child-Pugh score greater than 9) or in patients with hepatic impairment (Child-Pugh score less than 9) in whom a dose reduction of losartan to 25 mg is recommended. day (see sections “Pharmacological properties. Pharmacokinetics”, “Contraindications”, “Dosage and administration”).
Since amlodipine is mainly metabolized in the liver and T1/2 in patients with impaired liver function is 56 hours, when prescribing amlodipine to patients with severe liver failure, dose titration should be carried out gradually.
Patients with kidney failure
Due to inhibition of the RAAS, some predisposed patients taking losartan experienced changes in renal function that were reversible when the drug was discontinued.
In patients whose renal function may depend on the activity of the RAAS (for example, with CHF III-IV functional class according to the NYHA classification), the use of ACE inhibitors was accompanied by oliguria and/or increasing azotemia and, rarely, acute renal failure and/or death. A similar picture was observed with the use of losartan in such patients. Some drugs that affect the RAAS may increase plasma urea and serum creatinine concentrations in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney. A similar effect was observed when taking losartan in this group of patients; it was reversible when the drug was discontinued. Lortenza should be used with caution in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney.
Double blockade of the RAAS
Concomitant use of ARB II, including losartan, with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients.
Concomitant use of ARB II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
Hypertensive crisis
The effectiveness and safety of use in hypertensive crisis have not been established.
Special patient groups
Children and teenagers
The effectiveness and safety of Lortenza® in children and adolescents under 18 years of age have not been established.
If oliguria or hypotension develops in newborns whose mothers took Lortenza 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). In elderly patients, due to reduced clearance leading to an increase in amlodipine AUC by approximately 40-60%, amlodipine therapy is usually recommended to begin with a dose of 2.5 mg once daily. Since Lortenza® does not have a dosage containing amlodipine 2.5 mg, this dose should be prescribed as amlodipine monotherapy.
Special information on excipients
Lortenza® contains lactose, so it should not be used for the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.
Lortenza tablet p/o film 5mg+50mg 90 pcs
Patients with reduced blood volume or with severe aortic stenosis: Patients with reduced blood volume (for example, when taking high doses of diuretics, severe diarrhea, vomiting and other conditions leading to hypovolemia) or with severe aortic stenosis may develop symptomatic symptoms when starting therapy with Lortenza®. arterial hypotension. Correction of such conditions should be carried out before starting therapy or treatment should be started with a lower dose of Lortenza®. For patients whose daily dose of losartan is 25 mg, the use of Lortenza® is not recommended (see section “Dosage and Administration”). Special instructions and precautions related to amlodipine: Due to the prolonged T1/2, vasodilation that develops as a result of taking amlodipine may persist even after its discontinuation. Thus, the use of another vasodilator after discontinuation of amlodipine should be done with caution, individual assessment of the dose, dosing interval and active monitoring of the patient's condition are necessary. During the treatment period, it is necessary to control body weight and salt intake, and prescribe an appropriate diet. It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gum hyperplasia).
Unstable angina and myocardial infarction: After initiation of therapy or increasing the dose of amlodipine, unstable angina and acute myocardial infarction may develop, especially in patients with severe HOCM.
Special instructions and precautions related to losartan: Hyperkalemia (plasma potassium > 5.5 mmol/l) was observed in 1.5% of patients taking losartan as monotherapy. In none of these cases did the drug need to be discontinued. The simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride, eplerenone), potassium supplements, potassium-containing salt substitutes, as well as drugs that can lead to increased potassium levels in the blood plasma (for example, heparin) with losartan should be justified ( especially in elderly patients with impaired renal function), and the potassium content in the blood plasma should be monitored. While taking losartan, patients should not take potassium supplements or table salt substitutes containing potassium without first consulting their doctor. Taking losartan can lead to transient arterial hypotension, accompanied by shock, fainting and shortness of breath.
The drug Lortenza® should be used with caution in patients: - with reduced blood volume; - those on a diet with limited salt.
Hypersensitivity reactions: In patients with a history of angioedema (swelling of the larynx, vocal cords, face, lips, pharynx and/or tongue), the use of Lortenza® should be carefully monitored (see section "Side effects").
Embryotoxicity: The use of drugs that affect the RAAS in the II-III trimesters of pregnancy reduces fetal renal function and increases the incidence of morbidity and mortality in the fetus and newborn. The development of oligohydramnios may be associated with fetal lung hypoplasia and skeletal deformation. Possible adverse events in neonates include calvarial hypoplasia, anuria, hypotension, renal failure and death. If pregnancy is diagnosed, Lortenza® should be discontinued immediately (see section “Use during pregnancy and breastfeeding”).
Fluid and electrolyte imbalance: 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. Laboratory and instrumental data”).
Aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy: Like all drugs with a vasodilating effect, ARA II should be used with caution in patients with aortic or mitral stenosis, HOCM.
Chronic heart failure: 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 arterial hypotension or acute renal impairment. Since there is insufficient experience with the use of losartan in patients with CHF and concomitant severe renal impairment, in patients with severe heart failure (NYHA functional class III-IV), as well as in patients with heart failure and symptomatic life-threatening arrhythmias, Lortenza ® should be used with caution. In patients with CHF of functional class III-IV (according to the NYHA classification) of non-ischemic origin, an increased incidence of pulmonary edema was observed during the use of amlodipine, despite the absence of signs of worsening heart failure.
Coronary heart disease 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.
Primary hyperaldosteronism: Because patients with primary hyperaldosteronism generally do not respond well to antihypertensive agents that act by inhibiting the RAAS, the use of Lortenza is not recommended in this group of patients.
Patients with hepatic impairment: Data from pharmacokinetic studies indicate that patients with cirrhosis experience a significant increase in plasma concentrations of losartan. Lortenza should not be used in patients with severe hepatic impairment (Child-Pugh score greater than 9) or in patients with hepatic impairment (Child-Pugh score less than 9) in whom a dose reduction of losartan to 25 mg is recommended. day (see sections “Pharmacological properties. Pharmacokinetics”, “Contraindications”, “Dosage and administration”). Since amlodipine is mainly metabolized in the liver and T1/2 in patients with impaired liver function is 56 hours, when prescribing amlodipine to patients with severe liver failure, dose titration should be carried out gradually.
Patients with renal impairment: Due to inhibition of the RAAS, some predisposed patients treated with losartan experienced changes in renal function that were reversible when the drug was discontinued. In patients whose renal function may depend on the activity of the RAAS (for example, with CHF III-IV functional class according to the NYHA classification), the use of ACE inhibitors was accompanied by oliguria and/or increasing azotemia and, rarely, acute renal failure and/or death. A similar picture was observed with the use of losartan in such patients. Some drugs that affect the RAAS may increase plasma urea and serum creatinine concentrations in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney. A similar effect was observed when taking losartan in this group of patients; it was reversible when the drug was discontinued. Lortenza should be used with caution in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney.
Dual blockade of the RAAS: Concomitant use of II ARBs, including losartan, with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients. Concomitant use of ARB II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
Hypertensive crisis: The effectiveness and safety of use in hypertensive crisis have not been established.
Children and adolescents: The effectiveness and safety of Lortenza® in children and adolescents under 18 years of age have not been established. If oliguria or hypotension develops in newborns whose mothers took Lortenza 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 differences regarding the safety and effectiveness of losartan in elderly patients (over 65 years of age). In elderly patients, due to reduced clearance leading to an increase in amlodipine AUC by approximately 40-60%, amlodipine therapy is usually recommended to begin with a dose of 2.5 mg once daily. Since Lortenza® does not have a dosage containing amlodipine 2.5 mg, this dose should be prescribed as amlodipine monotherapy.
Special information on excipients: Lortenza® contains lactose, so it should not be used in the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.
Effect on driving vehicles and machinery Care should be taken when driving vehicles and working with other technical devices that require increased concentration and speed of psychomotor reactions, taking into account the risk of developing dizziness.
