Lortenza pills 10mg + 50mg, 30pcs

Composition

for 1 tablet 5 mg + 50 mg

Core:

Active ingredients:

Amlodipine Besylate (Amlodipine besylate) 6.94 mg, equivalent to Amlodipine 5.00 mg

Losartan A, substance-granules 163.55 mg, contains losartan potassium 50.00 mg

Excipients: cellactose 801, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, yellow iron oxide (E 172) dye, colloidal silicon dioxide, magnesium stearate

Film shell:

Opadray II white 2, iron oxide dye yellow (E 172), iron oxide dye red (E 172)

per 1 tablet 5 mg + 100 mg

Core:

Active ingredients:

Amlodipine Besylate (Amlodipine besylate) 6.94 mg, equivalent to Amlodipine 5.00 mg

Losartan A, substance-granules 327.10 mg, contains losartan potassium 100.00 mg

Auxiliary substances: cellulose 801, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, yellow iron oxide (E 172) dye, colloidal silicon dioxide, magnesium stearate

Film shell:

Opadray II white 2, iron oxide red dye (E 172)

for 1 tablet of 10 mg + 50 mg

Core:

Active ingredients:

Amlodipine Besylate (Amlodipine besylate) 13.88 mg, equivalent to Amlodipine 10.00 mg

Losartan A, substance-granules 163.55 mg, contains losartan potassium 50.00 mg

Auxiliary substances: cellulose 801, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, yellow iron oxide (E 172) dye, colloidal silicon dioxide, magnesium stearate

Film shell:

Opadray II white 2, iron oxide red dye (E 172)

per 1 tablet 10 mg + 100 mg

Core:

Active ingredients:

Amlodipine Besylate (Amlodipine besylate) 13.88 mg, equivalent to Amlodipine 10.00 mg

Losartan A, substance-granules 327.10 mg, contains losartan potassium 100.00 mg

Auxiliary substances: cellulose 801, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, yellow iron oxide (E 172) dye, colloidal silicon dioxide, magnesium stearate

Film shell:

Opadray II white 2, iron oxide yellow dye (E 172)

1 Cellactose 80: lactose monohydrate, cellulose.

2 Opadray II white: polyvinyl alcohol, titanium dioxide (E171), macrogol, talc.

Pharmacological action

combined antihypertensive agent (slow calcium channel blocker + angiotensin II receptor antagonist)

Clinical Pharmacology

Pharmacodynamics

Lortenza® is a combination of two active substances with complementary antihypertensive effects: amlodipine (slow calcium channel blocker) and losartan (angiotensin II receptor antagonist (ARA II)). The active ingredients of the drug have a different mechanism of antihypertensive action: amlodipine causes vasodilation, reducing total peripheral vascular resistance (OPSS), losartan affects the renin-angiotensin-aldosterone system (RAAS) (inhibits the effects of angiotensin II), which leads to a more pronounced decrease in blood pressure (BP) compared to that against the background of monotherapy with each drug.

Amlodipine

Amlodipine is a dihydropyridine derivative that blocks “slow” calcium channels and reduces the transmembrane flow of calcium ions into cardiomyocytes and vascular smooth muscle cells. The antihypertensive effect of amlodipine is associated with a direct relaxing effect on the smooth muscles of arterial vessels. In preclinical studies, amlodipine had a more pronounced effect on vascular smooth muscle cells compared to cardiomyocytes. Amlodipine has no negative effect on either atrioventricular conduction or myocardial contractility. Reduces the resistance of kidney vessels and increases renal blood flow.

Studies of amlodipine in patients with chronic heart failure (CHF) of functional class II-IV according to the NYHA classification (classification of the New York Heart Association) have shown that amlodipine does not adversely affect exercise tolerance, ejection fraction, or plasma lipid and glucose concentrations. After a single oral dose of amlodipine, the effect begins in 2-4 hours and persists for 24 hours. The maximum antihypertensive effect is achieved no earlier than 4 weeks after the start of therapy. Amlodipine reduces blood pressure in patients who are in the “lying” and “sitting” positions, as well as during physical exertion. Due to the gradual development of the pharmacodynamic effect, amlodipine does not cause a sharp decrease in blood pressure or reflex tachycardia. Amlodipine reduces the severity of left ventricular hypertrophy. The hemodynamic effects remain unchanged with long-term use of amlodipine.

Losartan

Losartan-synthetic ARA II (type AT₁) for oral use. Angiotensin II is a powerful vasoconstrictor, the main active hormone of RAAS and an important determining pathophysiological link in the development of arterial hypertension (AH). Angiotensin II binds to AT1receptors found in many tissues (vascular smooth muscle, adrenal glands, kidneys, and heart) and performs important biological functions, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of vascular smooth muscle cells.

Losartan selectively blocks AT_-1receptors. Losartan and its pharmacologically active carboxylated metabolite (E-3174), both in vitroand in vivo, block all physiological effects of angiotensin II, regardless of the source or route of its synthesis.

Losartan does not have agonist properties and does not block the receptors of other hormones or ion channels involved in the regulation of cardiovascular activity. Losartan does not inhibit the angiotensin-converting enzyme (ACE) that breaks down bradykinin. Accordingly, it does not cause an increase in the frequency of undesirable effects mediated by bradykinin.

Inhibition of regulation of renin secretion by angiotensin II by the mechanism of “negative” feedback during losartan treatment causes an increase in plasma renin activity (ARP), which leads to an increase in the concentration of angiotensin II in blood plasma. However, the antihypertensive effect and a decrease in the concentration of aldosterone in blood plasma remain, indicating an effective blockade of AT1receptors. After discontinuation of losartan, the ARP of blood and the concentration of angiotensin II in blood plasma decrease within 3 days to the initial values.

Pharmacokinetics

Amlodipine

Suction

When taken orally in therapeutic doses, amlodipine is well absorbed. The maximum concentration (cmax) in the blood plasma is reached after 6-12 hours. Absolute bioavailability ranges from 64% to 80%. Food intake does not affect the absorption of amlodipine.

Distribution

The volume of distribution₍vd) is about 21 l/kg. Steady-state plasma concentrations are reached 7-8 days after starting the drug. Binding to plasma proteins is 98%.

Metabolism

Amlodipine undergoes slow but active metabolism in the liver in the absence of a significant “primary passage” effect. The metabolites do not have significant pharmacological activity.

Deduction

The final half-life (T_1/2) from the blood plasma is 30-40 hours. The plasma clearance is 7 ml/min/kg. Approximately 60% of the metabolites and 10% of amlodipine unchanged are excreted by the kidneys,20-25% – through the intestine.

Pharmacokinetics of special patient groups

Patients with impaired liver function

Experience with amlodipine in patients with hepatic impairment is limited. In patients with impaired liver function, an elongation of T_{1/2 is noted}.

Losartan

Suction

After oral use, losartan is well absorbed. The systemic oral bioavailability of losartan is approximately 33%. _{Cmax of}losartan and its active metabolite in blood plasma is reached in 1 hour and in 3-4 hours, respectively.

Distribution

Losartan and its active metabolite are 99% bound to plasma proteins (mainly albumin). The V_d of losartan is 34 liters.

Metabolism

Losartan is metabolized during its “primary passage” through the liver to form the active carboxylated metabolite (E-3174) and other inactive metabolites.

Approximately 14% of the dose of losartan administered intravenously or taken orally is converted to its active metabolite. After oral or intravenous use of radiocarbon-labeled losartan potassium (14C losartan), most of the radiolabeled blood flow was consistent with losartan and its active metabolite. Minimal biotransformation of losartan to its active metabolite was observed in approximately 1% of patients who participated in clinical trials.

Deduction

The plasma clearance of losartan and its active metabolite is 600 ml / min and 50 ml/min, respectively.The renal clearance of losartan and its active metabolite was 74 ml / min and 26 ml / min, respectively. When losartan is taken orally, about 4% of the dose is excreted unchanged by the kidneys and 6% of the dose is excreted by the kidneys as an active metabolite. The pharmacokinetics of losartan and its active metabolite are linear when taken orally at doses up to 200 mg.

When taken orally, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final T_1/2 of about 2 hours and 6-9 hours, respectively. At a dose of 100 mg taken once a day, neither losartan nor its active metabolite accumulate in blood plasma. Losartan and its metabolites are excreted by the kidneys and through the intestines with bile. After ingestion of 14C losartan in men, about 35% of radioactivity is detected in the urine and 58% in the feces. After intravenous use of 14C losartan in men, approximately 43% of radioactivity is detected in the urine and 50% in the feces.

Pharmacokinetics of special patient groups

Elderly patients

The plasma concentrations of losartan and its active metabolite in elderly patients with hypertension do not significantly differ from those in young patients with hypertension.

Gender

The plasma concentrations of losartan in women with hypertension were 2 times higher than the corresponding values in men with hypertension. The concentrations of the active metabolite in men and women did not differ.

Patients with impaired liver function

In patients with mild and moderate alcoholic cirrhosis of the liver, when taking losartan orally, the concentrations of losartan and its active metabolite in blood plasma increased by 5 and 1.7 times, respectively (in comparison with similar indicators in young healthy male volunteers).

Patients with impaired renal function

The concentration of losartan in blood plasma does not change in patients with creatinine clearance (CC) greater than 10 ml/min. The area under the concentration-time curve (AUC) of losartan in patients on hemodialysis was approximately 2 times higher than the AUC of losartan in patients with normal renal function. Plasma concentrations of the active metabolite did not change in patients with impaired renal function or in patients undergoing hemodialysis. Losartan and its active metabolite are not eliminated by hemodialysis.

Indications

Arterial hypertension (patients who are indicated for combination therapy with amlodipine and losartan).

Use during pregnancy and lactation

Pregnancy

The use of Lortenza® during pregnancy is contraindicated, if pregnancy occurs, you should immediately stop taking the drug.

Drugs that affect the RAAS can cause damage and death of the fetus and newborn when used in pregnant women. Isolated cases of use of ACE inhibitors during pregnancy are described.

The use of drugs that directly affect the RAAS in the second and third trimesters of pregnancy is associated with such fetal injuries and complications in newborns as arterial hypotension, neonatal hypoplasia of the skull bones, anuria, and reversible and irreversible renal failure. There have also been cases of oligohydramnion, which is suspected to have developed as a result of reduced renal function in the fetus. In these cases, oligohydramnion was associated with limb contractures, craniofacial deformities, and fetal lung hypoplasia. In addition, there were cases of preterm labor, intrauterine growth retardation, and non-closure of the ductus arteriosus, but no association with the use of ARA II was found in these cases. The listed side effects, apparently, are not a consequence of the use of ARA II in the first trimester of pregnancy. Pregnant women who took ARA II drugs in the first trimester of pregnancy should be informed about the consequences of taking ARA II drugs in the second and third trimesters of pregnancy.

Depending on the duration of pregnancy, it is possible to use a stress test, a non-stress test, or a biophysical profile of the fetus to assess the functional state of the fetus. Patients and the doctor should be aware that oligohydramnion develops when the fetus is permanently damaged. Newborns whose mothers took ARA II during pregnancy should be under medical supervision, taking into account the risk of hypotension, oliguria and hyperkalemia. With the development of oliguria, first of all, correction of blood pressure and renal perfusion is necessary. Exchange blood transfusion or hemodialysis is necessary to correct arterial hypotension and / or to replace renal function.

Amlodipine

The safety of using amlodipine during pregnancy has not been established. In animal experiments, signs of reproductive toxicity were observed with the use of high doses of amlodipine. The use of amlodipine during pregnancy is possible in the absence of safe antihypertensive alternative therapy, and if the potential benefit to the mother exceeds the possible risk to the fetus.

Losartan

The use of drugs acting on the RAAS in the second and third trimesters of pregnancy can cause serious damage or even death of the fetus, so when planning pregnancy or when it occurs, losartan should be discontinued and, if necessary, transferred to alternative antihypertensive therapy, taking into account the safety profile. Renal perfusion in the fetus, which depends on RAAS, develops from the second trimester of pregnancy, so the risk for the fetus increases when taking losartan in the second and third trimesters of pregnancy.

Breast-feeding period

In preclinical animal studies, significant concentrations of amlodipine and/or the active metabolite of losartan in breast milk have been observed.

Amlodipine is excreted in breast milk. The proportion of maternal dose received by the children varies between 3-7%, with a maximum of 15%. The effect of amlodipine on children is unknown.

The use of Lortenza® is contraindicated during breastfeeding.

Fertility

Amlodipine

In some patients, reversible biochemical changes in the sperm head were observed during the use of BMCC. There is insufficient clinical data on the potential effect of amlodipine on fertility. It was reported that a rat study revealed a side effect on the fertility of male rats.

Losartan

In vitro and in vivo studies did not reveal the mutagenic properties of losartan. The fertility and reproductive function of male rats treated with oral doses up to 150 mg/kg/day did not change. When female rats were given doses of 100 mg / kg / day or more, a decrease in the number of yellow bodies, embryos and embryos was observed.

Contraindications

·  Hypersensitivity to active substances and / or auxiliary components of the drug.

* Pregnancy and lactation (see section “Use during pregnancy and lactation”).

·  Severe liver failure (more than 9 points on the Child-Pugh scale).

* Obstruction of the outflow tract of the left ventricle (for example, hemodynamically pronounced aortic stenosis).

* Hemodynamically unstable heart failure after acute myocardial infarction.

·  Shock (including cardiogenic shock).

·  Age up to 18 years (efficacy and safety have not been established).

·  Severe arterial hypotension (systolic blood pressure less than 90 mm Hg).

·  Severe renal impairment (creatinine clearance less than 20 ml / min), use in patients undergoing hemodialysis.

• Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or moderate to severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 of body surface area).
• Concomitant use with ACE inhibitors in patients with diabetic nephropathy.

· Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Interaction

The antihypertensive effect of Lortenza may be enhanced by concomitant use with other antihypertensive agents. Therefore, the simultaneous use of various antihypertensive agents should be justified.

Amlodipine

Concomitant use of amlodipine with thiazide diuretics, alpha-blockers or ACE inhibitors is considered safe.

Unlike other BMCs, no clinically significant interaction of amlodipine (third generation BMCs) was found when co-administered with nonsteroidal anti-inflammatory drugs (NSAIDs), including with indomethacin.

It is possible to increase the antihypertensive effect of BMCC when used simultaneously with thiazide and loop diuretics, ACE inhibitors and nitrates, as well as when used simultaneously with alpha-1-blockers, neuroleptics.

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 diltiazemat a dose of 180 mg per day and amlodipine at a dose of 5 mg per day in elderly patients, systemic exposure to amlodipine increases by 60%. Erythromycin, when used concomitantly, increases the_cmax of amlodipine in blood plasma in young patients by 22%, and in elderly patients-by 50%. At the same time, powerful inhibitors of the CYP3A4 isoenzyme(ketoconazole, itraconazole, ritonavir) may increase the concentration of amlodipine in the blood plasma to an even greater extent.

With simultaneous use of inducers of the CYP3A4 isoenzyme, the concentration of amlodipine in blood plasma may vary. Therefore, blood pressure monitoring and dose adjustment should be performed both during and after their simultaneous use, especially in combination with powerful inducers of the CYP3A4 isoenzyme (for example, rifampicin, St. John’s wort preparations).

Beta-blockers, when used concomitantly with amlodipine, can cause an exacerbation of the course of CHF.

Although no negative inotropic effects have usually been observed in studies of amlodipine, however, some BMCs may increase the severity of the negative inotropic effects of antiarrhythmic agents that cause prolongation of the QT interval (for example, amiodarone and quinidine).

A single dose of 100 mg of sildenafil in patients with hypertension does not affect the pharmacokinetics of amlodipine. When taking amlodipine simultaneously with sildenafil, each of the drugs independently exerted its own antihypertensive effect.

Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg was not accompanied by significant changes in the pharmacokinetics of atorvastatin.

Ethanol (alcoholic beverages): amlodipine does not affect the pharmacokinetics of ethanol with a single or repeated dose of 10 mg.

Neuroleptics and isoflurane enhance the antihypertensive effect of dihydropyridine derivatives.

When dantrolene is administered intravenously with amlodipine therapy, collapse, arrhythmias, decreased heart rate, and hyperkalemia are possible.

Calcium supplements may reduce the antihypertensive effect of BMCC.

When amlodipine is used concomitantly with lithium preparations, it is possible to increase the manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

It does not affect the serum concentration of digoxin and its renal clearance.

It does not significantly affect the effect of warfarin (in particular, simultaneous use of amlodipine and warfarin does not affect the increase in prothrombin time).

Cimetidine does not affect the pharmacokinetics of amlodipine.

In vitro studies, amlodipine did not affect the binding of digoxin, phenytoin, warfarin, and Indometacin to plasma proteins.

Simultaneous single use of 240 mg grapefruit juice and 10 mg 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 significantly affect the pharmacokinetics of amlodipine.

When co-administered with amlodipine, there is a risk of increasing the concentration of tacrolimus in blood plasma, but the pharmacokinetic mechanism of this interaction is not fully understood. To prevent the toxic effect of tacrolimus when used concomitantly with amlodipine, the concentration of tacrolimus in blood plasma should be monitored and, if necessary, its dose adjusted.

Clarithromycin is an inhibitor of the CYP3A4 isoenzyme. Concomitant use of amlodipine and clarithromycin increases the risk of hypotension. Careful medical monitoring of patients receiving amlodipine concomitantly with clarithromycin is recommended.

Mammalian mechanistic target inhibitors of rapamycin( mTOR): mTOR inhibitorssuch as sirolimus, temsirolimus, and everolimusare substrates of the CYP3A isoenzyme. Amlodipine is a weak inhibitor of the CYP3A isoenzyme. When used concomitantly with mTOR inhibitors, amlodipine may increase their exposure.

Drug interaction studies with cyclosporine and amlodipine in healthy volunteers or other groups of patients have not been conducted, except for patients who underwent kidney transplantation, who had variable minimum concentrations (average values: 0-40%) of cyclosporine. Concomitant use of amlodipine with cyclosporine may increase the concentration of cyclosporine in blood plasma. When amlodipine is used concomitantly in patients undergoing kidney transplantation, the concentration of cyclosporine in blood plasma should be monitored, and, if necessary, its dose should be reduced.

Clinical interaction studies have shown that amlodipine does not affect the pharmacokinetics of atorvastatin, digoxin or warfarin.

Simultaneous multiple use of 10 mg amlodipine and 80 mg simvastatin resulted in a 77% increase in simvastatin exposure. The dose of simvastatin when used concomitantly with amlodipine should not exceed 20 mg once a day.

Losartan

As with other agents that block the formation of angiotensin II and its effects, the simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride, eplerenone), potassium preparations and potassium-containing salt substitutes may lead to an increase in serum potassium.

As with other drugs that affect the excretion of sodium, losartan may reduce the excretion of lithium, so when lithium and ARA II preparations are used simultaneously, it is necessary to carefully monitor the concentration of lithium in the blood serum.

In some patients with impaired renal function (e. g., elderly or dehydrated patients, including those taking diuretics) who have been treated with NSAIDs, includingselective cyclooxygenase-2 (COX-2)inhibitors, concomitant use of ACE inhibitors and/orARA II, including losartan, can cause further deterioration of renal function up to the development of acute renal failure (ARF). This effect is usually reversible. NSAIDs, including selective COX-2 inhibitors, may reduce the effect of ARA II, including losartan. Therefore, the antihypertensive effect of ARA II may be weakened by concomitant use of NSAIDs, in particular selective COX-2 inhibitors. Therefore, concomitant use of the combination of amlodipine / losartan with NSAIDs should be carried out with caution in patients with impaired renal function.

Double blockade of the RAAS is possible only in some cases with careful monitoring of blood pressure, renal function, and blood plasma electrolytes. In patients with atherosclerosis, CHF, or diabetes mellitus with target organ damage, double blockade of the RAAS is associated with a higher incidence of hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared to the use of the drug in one of the listed groups.

Concomitant use of ARA II, including losartan, with drugs containing aliskirenis contraindicated in patients with diabetes mellitus and/or moderate to severe renal impairment (GFR less than 60 ml/min / 1.73 m2 of body surface area) and is not recommended in other patients.

Concomitant use of ARA II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

There were no pharmacokinetically significant interactions of losartan with such drugs as hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital. Rifampicin, an inducer of drug metabolism, reduces plasma concentrations of losartan and its active metabolite.

The use of two inhibitors of the CYP3A4 isoenzyme was studied in clinicaltrials. Ketoconazole did not affect the metabolism of losartan to the active metabolite after intravenous use of losartan. Erythromycin did not have a clinically significant effect on the oral pharmacokinetics of losartan.

Fluconazole, an inhibitor of the CYP2C9 isoenzyme, reduces the concentration of the active metabolite of losartan and increases the concentration of losartan in blood plasma, but the pharmacodynamic significance of concomitant use of losartan and inhibitors of the CYP2C9 isoenzyme has not been established. Patients who do not metabolize losartan to the active metabolite have been shown to have a very rare and specific defect in the CYP2C9 isoenzyme. These data indicate that the metabolism of losartan to the active metabolite is mediated primarily by the CYP2C9 isoenzyme, and not by the CYP3A4 isoenzyme.

How to take it, course of use and dosage

Inside,1 time a day, regardless of the meal time, with a small amount of water.

The recommended dose of Lortenza® is 1 tablet per day.

Lortenza® 5 mg + 50 mg is prescribed to patients who have not achieved adequate blood pressure control when using amlodipine 5 mg or losartan 50 mg in monotherapy.

Lortenza® at a dose of 5 mg + 100 mg is prescribed to patients who have not achieved adequate blood pressure control when using losartan at a dose of 100 mg or Lortenza® at a dose of 5 mg + 50 mg.

Lortenza ® 10 mg + 50 mg is prescribed to patients who have not achieved adequate blood pressure control with amlodipine 10 mg or Lortenza® 5 mg + 50 mg.

Lortenza® at a dose of 10 mg + 100 mg is prescribed to patients who have not achieved adequate blood pressure control when using Lortenza® at a dose of 5 mg + 100 mg or 10 mg + 50 mg.

The dose is selected after previously titrated doses of individual components of the drug. If you need to change the dose of one of the active ingredients in a fixed combination drug (for example, due to a newly diagnosed disease, a change in the patient’s condition, or a drug interaction), individual selection of doses of individual components is necessary.

The maximum daily dose of Lortenza® is 10 mg + 100 mg.

Patients taking losartan and amlodipine at the same time may be switched to Lortenza®, which contains losartan and amlodipine in the same doses.

Impaired renal function

No dose adjustment is required for creatinine clearance from 50 to 20 ml/min.

Lortenza® is contraindicated in patients with creatinine clearance less than 20 ml / min and in patients undergoing hemodialysis (see section “Contraindications”).

Patients with reduced BCC

In patients with reduced BCC (for example, due to treatment with high doses of diuretics, etc. ), the initial dose of losartan should be reduced to 25 mg once a day. Since Lortenza® does not have a dosage containing 25 mg of losartan, this dose should be administered in monotherapy with losartan.

Before using Lortenza®, it is necessary to restore the BCC and sodium content in the blood plasma.

Impaired liver function

Patients with a history of hepatic impairment (less than 9 points on the Child-Pugh scale) are recommended to use lower doses of losartan. Since Lortenza® does not have a dosage containing 25 mg of losartan, this dose should be administered in monotherapy with losartan.

The use of Lortenza® is possible in patients with impaired liver function (less than 9 points on the Child-Pugh scale), who, according to the doctor’s decision, are recommended to use losartan at a dose of 50 mg.

Elderly patients

In elderly patients (older than 65 years) due to reduced clearance, amlodipine therapy is recommended to start with a dose of 2.5 mg once a day. Since Lortenza® does not have a dosage containing 2.5 mg of amlodipine, this dose should be administered in monotherapy with amlodipine.

Children and teenagers

Lortenza® should not be prescribed to children and adolescents under 18 years of age, as there are no data on the effectiveness and safety of use in this group of patients.

Overdose

Cases of overdose with a fixed combination of amlodipine/losartan are unknown. Overdose data on amlodipine and losartan taken separately are given below.

Description

Tablets 5 mg + 50 mg:

Oval, slightly biconvex tablets, covered with a film-coated light brown with an orange tinge of color.

View on the fracture: a rough mass consisting of two layers-white or almost white and pale yellow with a film shell of light brown with an orange tint.

Tablets 5 mg + 100 mg:

Oval, biconvex tablets, covered with a film-coated pink color.

View on the fracture: a rough mass consisting of two layers-white or almost white and pale yellow with a pink film shell.

Tablets 10 mg + 50 mg:

Oval, slightly biconvex tablets, covered with a film-coated red-brown color.

View on the fracture: a rough mass consisting of two layers-white or almost white and pale yellow with a red-brown film shell.

Tablets 10 mg + 100 mg:

Oval, biconvex tablets, covered with a film-coated pale brownish-yellow color.

View on the fracture: a rough mass consisting of two layers-white or almost white and pale yellow with a film shell of pale brownish-yellow color.

Special instructions

Bilateral renal artery stenosis or stenosis of the artery of a single kidney, post – kidney transplant condition (no experience), coronary heart disease (CHD), heart failure with life-threatening arrhythmias, cerebrovascular diseases, primary hyperaldosteronism, history of angioedema, unstable angina, use in patients with low circulating blood volume (BCC) (for example, when using high doses of diuretics, severe diarrhea, hyperkalemia, arterial hypotension, hepatic insufficiency (less than 9 points on the Child-Pugh scale), sinus node weakness syndrome (severe bradycardia, tachycardia), heart failure with concomitant severe renal dysfunction, severe CHF of non-ischemic etiology (III-IV functional class). NYHA classification), aortic and/or mitral stenosis, hypertrophic obstructive cardiomyopathy (HOCMP), acute myocardial infarction (and within 1 month after the infarction), concomitant use with inhibitors and inducers of the CYP3A4 isoenzyme, water-electrolyte balance disorders, renal failure (mild to moderate), use in elderly patients.

Lortenza® should not be prescribed to children and adolescents under 18 years of age, as there are no data on the effectiveness and safety of use in this group of patients.

Impaired renal function

No dose adjustment is required for creatinine clearance from 50 to 20 ml/min.

Lortenza® is contraindicated in patients with creatinine clearance less than 20 ml / min and in patients undergoing hemodialysis.

Impaired liver function

Patients with a history of hepatic impairment (less than 9 points on the Child-Pugh scale) are recommended to use lower doses of losartan. Since Lortenza® does not have a dosage containing 25 mg of losartan, this dose should be administered in monotherapy with losartan.

The use of Lortenza® is possible in patients with impaired liver function (less than 9 points on the Child-Pugh scale), who, according to the doctor’s decision, are recommended to use losartan at a dose of 50 mg.

Elderly patients

In elderly patients (older than 65 years) due to reduced clearance, amlodipine therapy is recommended to start with a dose of 2.5 mg once a day. Since Lortenza® does not have a dosage containing 2.5 mg of amlodipine, this dose should be administered in monotherapy with amlodipine.

Patients with reduced BCC or severe aortic stenosis

Patients with reduced BCC (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 hypotension at the beginning of therapy with Lortenza®. Correction of such conditions should be carried out before starting therapy or starting treatment with a lower dose of Lortenza®. For patients whose daily dose of losartan is 25 mg, the use of Lortenza® is not recommended (see the section “Dosage and use”).

Special instructions and precautions related to amlodipine

Due to prolonged T_1/2, the vasodilation that developed as a result of taking amlodipine may persist even after its withdrawal. Therefore, the use of another vasodilator after discontinuation of amlodipine should be carried out with caution, individual dose assessment, dosage 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, 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

Unstable angina and acute myocardial infarction may develop after starting therapy or increasing the dose of amlodipine, especially in patients with severe HOCMP.

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. None of these cases required drug withdrawal. The simultaneous use of potassium-sparing diuretics (e. g., spironolactone, triamterene, amiloride, eplerenone), potassium preparations, potassium-containing salt substitutes, and drugs, intake of which may lead to higher content of potassium in the blood plasma (e. g., 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 dietary salt substitutes containing potassium without prior consultation with their doctor.

Taking losartan may lead to transient hypotension, accompanied by shock, syncope, and shortness of breath.

Lortenza® should be used with caution in patients with:

· those with a reduced BCC;

· those on a diet with a restriction of table salt.

Hypersensitivity reactions

In patients with a history of angioedema (oedema 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 kidney function and increases the incidence of morbidity and mortality of the fetus and newborn. The development of oligohydramnios may be associated with fetal lung hypoplasia and skeletal deformity. Possible adverse events in newborns include cranial hypoplasia, anuria, hypotension, renal failure, and death. If pregnancy is diagnosed, Lortenza® should be discontinued immediately (see section “Use during pregnancy and lactation”).

Violation of the water-electrolyte balance

Impaired water-electrolyte balance is characteristic of patients with impaired renal function with or without diabetes mellitus, so careful monitoring of these patients is necessary. In clinical trials involving patients with type 2 diabetes mellitus with proteinuria, the incidence of hyperkalemia was higher in the losartan group than in the placebo group. Several patients discontinued therapy due to hyperkalemia (see the 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, HOCMP.

As with other drugs that have an effect 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 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.

Patients with non-ischemic CHF of functional class III-IV (NYHA classification) showed an increase in the incidence of pulmonary edema 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 CHD 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 usually do not show a positive response to therapy with antihypertensive agents that act by inhibiting RAAS, the use of Lortenza® is not recommended in this group of patients.

Patients with hepatic insufficiency

Data from pharmacokinetic studies indicate that patients with cirrhosis of the liver have a significant increase in the concentration of losartan in blood plasma. Lortenza® should not be used in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale), as well as in patients with hepatic insufficiency (less than 9 points on the Child-Pugh scale), who are recommended to reduce the dose of losartan to 25 mg per day (see the sections “Pharmacological properties. Pharmacokinetics”, “Contraindications”, “Method of use and doses”).

Since amlodipine is mainly metabolized in the liver and the T_1/2 in patients with impaired liver function is 56 hours, when prescribing amlodipine to patients with severe hepatic insufficiency, titration of the dose should be carried out gradually.

Patients with renal insufficiency

Due to RAAS inhibition, some predisposed patients taking losartan experienced reversible changes in renal function when the drug was discontinued.

In patients whose renal function may depend on RAAS activity (for example, in patients with NYHA functional class III-IV CHF), the use of ACE inhibitors has been associated with oliguria and/or increasing azotemia and, rarely, acute renal failure and/or death. A similar pattern was observed when using losartan in such patients. Some drugs that affect the RAAS may increase the concentration of urea in blood plasma and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the renal artery of a single 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 stenosis of the renal artery of a single kidney.

Double blockade of the RAAS

Concomitant use of ARA II, including losartan, with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to severe renal impairment (GFR less than 60 ml/min / 1.73 m2 of body surface area) and is not recommended in other patients.

Concomitant use of ARA II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Hypertensive crisis

The efficacy and safety of its use in hypertensive crisis have not been established.

Special patient groups

Children and teenagers

The efficacy and safety of Lortenza® in children and adolescents under 18 years of age have not been established.

If newborns whose mothers took Lortenza® during pregnancy develop oliguria or hypotension, 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 kidney function.

Elderly patients

Clinical studies have not revealed any specific features regarding the safety and efficacy of losartan in elderly patients (over 65 years of age). In elderly patients, due to reduced clearance resulting in an increase in amlodipine AUC by approximately 40-60%, amlodipine therapy is usually recommended to start with a dose of 2.5 mg once a day. Since Lortenza® does not have a dosage containing 2.5 mg of amlodipine, this dose should be administered in monotherapy with amlodipine.

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.

Caution should be exercised when driving vehicles and working with other technical devices that require increased concentration of attention and speed of psychomotor reactions, given the risk of dizziness.

Form of production

Film-coated tablets,5 mg + 50 mg,5 mg + 100 mg,10 mg + 50 mg,10 mg + 100 mg.

7 or 10 tablets in a contour cell package made of a combined OPA/Al/PVC material and aluminum foil.

1,2,4,8,12 contour cell packages (7 tablets each) or 1,3,6,9 contour cell packages (10 tablets each) together with the instructions for use are placed in a cardboard pack.

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging.

Keep out of reach of children.

Shelf

life is 2 years.

Do not use the drug after the expiration date.

Active ingredient

Amlodipine, Losartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension