Lortenza pills 5mg + 50mg №30

Trade name

Tradename: Lortenza

International non-proprietary or grouping name: amlodipine + Losartan

Dosage Form: film coated tablets

Compositions

on 1 pill 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 36.45 mg, microcrystalline cellulose 212.96 mg, pregelatinized starch 54.00 mg, sodium carboxymethyl starch

22.00 mg, iron dye yellow oxide (E172) 0.40 mg, colloidal silicon dioxide 1.60 mg, Magnesium stearate 5.10 mg

Shell film:

Opadry II white² 25.71 mg, iron dye yellow oxide (E172) 1.03 mg, iron dye red oxide (E172) 0.26 mg

on 1 pill 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

Excipients: cellactose 80¹ 36.45 mg, microcrystalline cellulose 206.02 mg, pregelatinized starch 54.00 mg, sodium carboxymethyl starch

22.00 mg, iron dye yellow oxide (E172) 0.40 mg, colloidal silicon dioxide 1.60 mg, magnesium stearate 5.10 mg

Shell film:

Opadry II white² 24.40 mg, iron dye red oxide (E172) 2.60 mg

on 1 pill 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

Excipients: cellactose 80¹ 72.90 mg, microcrystalline cellulose 212.96 mg, pregelatinized starch 54.00 mg, sodium carboxymethyl starch

22.00 mg, iron dye yellow oxide (E172) 0.40 mg, colloidal silicon dioxide 2.10 mg, magnesium stearate 6.60 mg

Shell film:

Opadry II white² 29.75 mg, iron dye red oxide (E172) 0.25 mg

on 1 pill of 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

Excipients: cellactose 80¹ 72.90 mg, microcrystalline cellulose 206.02 mg, pregelatinized starch 54.00 mg, sodium carboxymethyl starch

22.00 mg, iron dye yellow oxide (E172) 0.40 mg, colloidal silicon dioxide 2.10 mg, magnesium stearate 6.60 mg

Shell film:

Opadry II white² 29.00 mg, iron dye yellow oxide (E172) 1.00 mg

¹ Cellactose 80: lactose monohydrate (75%), cellulose (25%).

² Opadry II white: polyvinyl alcohol (40.0%), titanium dioxide (E171) (25.0%), macrogol (20.2%), talc (14.8%).

Description

Tablets 5 mg + 50 mg:

Oval, slightly biconvex tablets, film-coated light brown with an orange tint.

Tablets 10 mg + 50 mg:

Oval, slightly biconvex tablets, film-coated red-brown.

Tablets 5 mg + 100 mg:

Oval, biconvex tablets, film-coated pink color.

Tablets 10 mg + 100 mg:

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

Kind of pills on a break for all dosages: a rough mass of two

layers - white or almost white and light yellow.

Pharmacotherapeutic group: combined antihypertensive agent (blocker of “slow” Calcium channels + angiotensin II receptor antagonist)

Pharmacology

Pharmacodynamics

Lortenza is a combination of two active ingredients with an antihypertensive effect that complements each other: amlodipine (a “slow” calcium channel blocker) and losartan (an antagonist of angiotensin II receptors

(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 arterial pressure (BP) compared with that on the background of monotherapy for each drug.

Amlodipine

Amlodipine, a dihydropyridine derivative, blocks the “slow” calcium channels and reduces the transmembrane current of calcium ions in cardiomyocytes and vascular smooth muscle cells. The antihypertensive effect of amlodipine is associated with a direct relaxing effect on smooth muscle of the arterial vessels. In preclinical studies, amlodipine had a more pronounced effect on vascular smooth muscle cells compared with cardiomyocytes. Amlodipine does not adversely affect the atrioventricular conductivity or myocardial contractility. It reduces the resistance of the kidney vessels and increases the 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) showed that amlodipine does not adversely affect exercise tolerance, ejection fraction, or plasma lipid and glucose concentrations blood. After a single dose of amlodipine inside, the action begins after 2-4 hours and lasts for 24 hours. The maximum antihypertensive effect is achieved no earlier than 4 weeks after the start of therapy. Amlodipine lowers blood pressure in patients who are in the "lying" and "sitting" positions, as well as during exercise. 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. Hemodynamic effects remain unchanged with long-term use of amlodipine.

Losartan

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

Losartan selectively blocks AT₁receptors. Losartan and its pharmacologically active carboxylated metabolite (E-3174) as under conditions in vitroso in conditions in vivo block all the physiological effects of angiotensin II, regardless of the source or path of its synthesis.

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

Suppression of regulation of renin secretion under the action of angiotensin II by the mechanism of "negative" feedback in the treatment with losartan causes an increase in plasma renin activity (ARP)blood, which leads to an increase in the concentration of angiotensin II in the blood plasma. However, the antihypertensive effect and a decrease in the concentration of aldosterone in the blood plasma persist, indicating an effective blockade of AT₁-receptors. After cessation of losartan, the blood ARP and the concentration of angiotensin II in plasma decrease within 3 days to their original values.

Pharmacokinetics

Amlodipine

Suction

When administered in therapeutic doses, amlodipine is well absorbed. Maximum concentration (C_max) in blood plasma is reached after 6-12 hours. Absolute bioavailability ranges from 64% to 80%. Eating does not affect the absorption of amlodipine.

Distribution

Distribution Volume (V_d) is about 21 l / kg. Equilibrium plasma concentrations are reached after 7-8 days after the start of the drug. Binding to plasma proteins - 98%.

Metabolism

Amlodipine undergoes a slow, but active metabolism in the liver in the absence of a significant “first pass” effect. Metabolites do not have significant pharmacological activity.

Removal

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

Pharmacokinetics of special groups of patients

Patients with impaired liver function

Experience with amlodipine in patients with impaired liver function is limited. In patients with impaired liver function, T is lengthened._1/2.

Losartan

Suction

After oral administration, losartan is well absorbed. Systemic bioavailability of losartan when administered orally is approximately 33%. C_max losartan and its active metabolite in the blood plasma are reached after 1 hour and 3-4 hours, respectively.

Distribution

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

Metabolism

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

Approximately 14% of a dose of losartan, administered intravenously or ingested, is converted to its active metabolite.After ingestion or intravenous administration of radiolabeled losartan potassium (¹⁴With losartan), most of the radioactive label in the bloodstream corresponded to losartan and its active metabolite. The minimum level of biotransformation of losartan in its active metabolite was observed in approximately 1% of patients who participated in clinical studies.

Removal

The plasma clearance of losartan and its active metabolite is 600 ml / min and

50 ml / min, respectively. Renal clearance of losartan and its active metabolite -

74 ml / min and 26 ml / min, respectively. When losartan is taken orally, about 4% of the dose is excreted by the kidneys unchanged 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 in doses up to 200 mg.

When taken orally, the concentration of losartan and its active metabolite in blood plasma decreases polyexponentially with a final T_1/2 about 2 hours and 6-9 hours, respectively. At a dose of 100 mg taken once a day, neither losartan nor its active metabolite is accumulated in the blood plasma. Losartan and its metabolites are excreted by the kidneys and through the intestines with bile. When taken orally and intravenously ¹⁴About 35% and 43% of radioactivity, respectively, of losartan and its active metabolite were excreted by the kidneys and 58% and 50% from the human losartan through the intestines, respectively.

Pharmacokinetics of special groups of patients

Elderly patients

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

Floor

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 concentration of losartan and its active metabolite in the blood plasma increased 5 and 1.7 times, respectively, compared with similar indicators in young healthy male volunteers.

Patients with impaired renal function

Plasma losartan concentration does not change in patients with creatinine clearance (CK) of more than 10 ml / min.The area under the concentration-time curve (AUC) of losartan in patients on hemodialysis was about 2 times higher than that 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 on hemodialysis. Losartan and its active metabolite are not excreted by hemodialysis.

Indications for use

Arterial hypertension (to patients who are shown combination therapy with amlodipine and losartan).

Contraindications

• Hypersensitivity to active ingredients and / or auxiliary components of the drug.
• Pregnancy and breastfeeding period (see section “Use during pregnancy and during breastfeeding”).
• Severe liver failure (more than 9 points on the Child-Pugh scale).
• Hemodynamically pronounced stenosis of the mouth of the aorta.
• 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. Art.).
• Severe renal dysfunction (CC less than 20 ml / min), use in patients on hemodialysis.

• Simultaneous use with aliskiren in patients with diabetes mellitus or renal dysfunction (QA less than 60 ml / min).

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

Carefully: bilateral renal artery stenosis or arterial stenosis of a single kidney, condition after kidney transplantation (no experience), coronary heart disease, heart failure with life-threatening arrhythmias, cerebrovascular diseases, primary hyperaldosteronism, angioedema in history, unstable angina, patients in patients with angioedema, unstable angina, the volume of circulating blood (BCC) (for example, when using high doses of diuretics, severe diarrhea, vomiting, and other conditions leading to hypovola s), in patients who are on a diet with restriction of salt, hyperkalemia, hypotension, liver failure (less than 9 points on a scale Child-Pugh)sick sinus syndrome (severe bradycardia, tachycardia), non-ischemic etiology of CHF (NYHA class II-IV functional class), aortic and / or mitral stenosis, hypertrophic obstructive cardiomyopathy (GOMP), acute myocardial infarction (and within 1 month after infarction) ), use in elderly patients.

Use during pregnancy and during breastfeeding

Pregnancy

Use of the drug Lortenza during pregnancy is contraindicated, when pregnancy occurs, you should immediately stop taking the drug.

Drugs (drugs) that affect the RAAS, can cause damage and death of the fetus and newborn when used in pregnant women. Described isolated cases of use of ACE inhibitors during pregnancy.

The use of drugs that directly affect the RAAS in the second and third trimesters of pregnancy is associated with fetal damage and complications in the newborn, such as arterial hypotension, neonatal hypoplasia of the skull bones, anuria, reversible and irreversible renal failure. Also reported cases of oligohydramnios, presumably developed as a result of reduced kidney function in the fetus. In these cases, oligohydramnios was associated with contractures of the extremities, craniofacial deformities, and hypoplasia of the fetal lungs. In addition, there were cases of premature birth, intrauterine growth retardation and non-closure of the ductus arteriosus, however, no connection was detected with the use of APA II in these cases. These side effects, apparently, are not the result of the use of APA 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 in the second and third trimesters of pregnancy.

Depending on the duration of pregnancy, a stress test, a non-stress test, or the determination of the biophysical profile of the fetus can be used to assess the functional status of the fetus. Patients and the physician should be aware that oligohydramnios develops with irreversible damage to the fetus. Newborns whose mothers took ARA II during pregnancy should be under medical supervision, taking into account the risk of arterial hypotension, oliguria and hyperkalemia.With the development of oliguria, first of all, correction of blood pressure and renal perfusion is necessary. Exchange hemotransfusion or hemodialysis is necessary for the correction of arterial hypotension and / or for the replacement of renal function.

Amlodipine

The safety of using amlodipine during pregnancy has not been established. In animal studies, 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 outweighs the possible risk to the fetus.

Losartan

The use of drugs acting on the RAAS in the II and III trimesters of pregnancy can cause serious damage or even fetal death, so when planning a pregnancy or when it occurs, you should stop taking losartan and, if necessary, switch to alternative antihypertensive therapy with regard to the safety profile. Renal perfusion in the fetus, depending on the RAAS, develops from the second trimester of pregnancy, so the risk to the fetus increases when taking losartan in the second and third trimesters of pregnancy.

Breastfeeding period

It is not known whether the release of amlodipine and / or losartan into breast milk, in preclinical studies in animals, significant concentrations of amlodipine and / or an active metabolite of losartan in breast milk were observed.

Use of the drug Lortenza is contraindicated during breastfeeding.

Fertility

Amlodipine

In some patients with the use of calcium channel blockers, reversible biochemical changes of the sperm head were noted. Clinical data on the potential effect of amlodipine on fertility is insufficient. It was reported that a study on rats revealed a side effect on the fertility of male rats.

Losartan

In research in vitro and in vivo mutagenic properties of losartan not detected. Fertility and reproductive function of male rats receiving an oral dose up to

150 mg / kg / day, unchanged. With the introduction of doses of 100 mg / kg / day to female rats and more, a decrease in the number of corpus luteum, implants and embryos was observed.

Dosage and administration

Inside, 1 time per day, regardless of the time of eating, squeezed with a small amount of water.

The recommended dose of Lortenza is 1 pill per day.

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

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

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

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

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

The maximum daily dose is 10 mg + 100 mg.

Patients taking losartan and amlodipine at the same time can be transferred to the drug Lortenza containing losartan and amlodipine in the same doses.

Renal dysfunction

When QA from 50 to 20 ml / min dose adjustment is required.

Lortenza is contraindicated in patients with CC less than 20 ml / min and in patients on hemodialysis (see the “Contraindications” section).

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 1 time per day. In connection with the lack of a dosage of drug Lortenza containing 25 mg of losartan, this dose should be prescribed in losartan monotherapy.

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

Liver dysfunction

In patients with impaired function (less than 9 points on the Child-Pugh scale) in history, it is recommended to use lower doses of losartan. In connection with the lack of a dosage of drug Lortenza containing 25 mg of losartan, this dose should be prescribed in losartan monotherapy.

Use of the drug Lortenza is possible in patients with impaired liver function (less than 9 points on the Child-Pugh scale), who are recommended by the doctor to use losartan in a dose of 50 mg.

Elderly patients

Elderly patients do not require dose adjustment of Loretenza, however, it is necessary to increase the dose carefully.

Kids and teens

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

Side effect

Classification of the incidence of side effects of the World Health Organization (WHO):

very often ≥ 1/10

often from ≥ 1/100 to <1/10

infrequently from ≥ 1/1000 to <1/100

rarely from ≥ 1/10000 to <1/1000

very rarely <1/10000

frequency unknown cannot be estimated based on available data.