Lortenza, 5 mg+50 mg 90 pcs

Hypotensive drug combined (slow calcium channel blocker + angiotensin II receptor antagonist)

Indications

Arterial hypertension (patients treated with amlodipine and losartan combination therapy).

Active ingredient

Composition

for 1 tablet 5 mg + 50 mg

Kernel:

Active substances:

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

Lozartan A, 163.55 mg granule substance, contains losartan potassium 50.00 mg

Supplementary substances: 801 cellactose, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, iron oxide yellow dye (E172), colloidal silicon dioxide, magnesium stearate

Shell film:

Opadray II white2, iron oxide yellow dye (E172), iron oxide red dye (E172)

for 1 tablet 5 mg + 100 mg

Kernel:

Active substances:

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

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

Supplementary substances: cellactose 801, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, iron oxide yellow dye (E172), colloidal silicon dioxide, magnesium stearate

Shell film:

Opadray II white2, iron oxide red dye (E172)

for 1 tablet 10 mg + 50 mg

Kernel:

Active substances:

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

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

Supplementary substances: cellactose 801, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, iron oxide yellow dye (E172), colloidal silicon dioxide, magnesium stearate

Shell film:

Opadray II white2, iron oxide red dye (E172)

for 1 tablet 10 mg + 100 mg

Kernel:

Active substances:

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

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

Supplementary substances: cellactose 801, microcrystalline cellulose, pregelatinized starch, sodium carboxymethyl starch, iron oxide yellow dye (E172), colloidal silicon dioxide, magnesium stearate

Shell film:

Opadray II white2, iron oxide yellow dye (E172)

1 Cellactose 80: lactose monohydrate, cellulose.

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

How to take, the dosage

Orally, once daily, regardless of meal time, with a little water.

The recommended dose of Lortense® is 1 tablet daily.

Lortenza® in dose 5 mg + 50 mg is indicated for patients who have not adequately controlled BP when using amlodipine 5 mg or losartan 50 mg in monotherapy.

Lortenza® at a dose of 5 mg + 100 mg is indicated for patients who have not achieved adequate BP control when using losartan 100 mg or Lortenza® at a dose of 5 mg + 50 mg.

Lortenza® at a dose of 10 mg + 50 mg is indicated for patients who have not achieved adequate BP control when using amlodipine 10 mg or Lortenza® at a dose of 5 mg + 50 mg.

Lortenza® at a dose of 10 mg + 100 mg is indicated for patients who have not achieved adequate BP control when using Lortenza® at a dose of 5 mg + 100 mg or 10 mg + 50 mg.

The dose is adjusted after previously titrated doses of individual drug components. If it is necessary to change the dose of one of the active substances in the composition of the fixed combined medicine (for example, due to newly diagnosed disease, change in the patient’s condition or drug interaction), individual selection of doses of individual components is necessary.

Maximum daily dose of Lortense® is 10 mg + 100 mg.

Patients taking losartan and amlodipine concomitantly may be switched to Lortenza® containing losartan and amlodipine in the same doses.

Kidney function disorder

Dose adjustment is not required for CK of 50 to 20 ml/min.

The drug Lortenza® is contraindicated in patients with CK less than 20 ml/min and patients on hemodialysis (see section “Contraindications”).

Patients with reduced CPR

In patients with decreased RBC (eg, due to high-dose diuretic treatment, etc.) the starting dose of losartan should be reduced to 25 mg once daily. Due to the unavailability of Lortenza® containing 25 mg losartan, this dose should be administered in losartan monotherapy.

Before using Lortensa®, the RBC and plasma sodium content should be restored.

Liver function disorder

Patients with a history of liver dysfunction (less than 9 on the Child-Pugh score) are recommended to use a lower dose of losartan. Due to the absence of a Lortenza® dosage containing 25 mg losartan, this dose should be administered in losartan monotherapy.

The use of the drug Lortenza® is possible in patients with impaired liver function (less than 9 points by Child-Pugh score) for whom the use of losartan in a dose of 50 mg has been recommended by a physician.

Elderly patients

In elderly patients (>65 years) due to decreased clearance, therapy with amlodipine should be started with a 2.5 mg dose once daily. Since Lortenza® has no dosage containing 2.5 mg amlodipine, this dose should be administered in amlodipine monotherapy.

Children and teens

The drug Lortenza® should not be administered to children and adolescents younger than 18 years of age, because there are no data on the effectiveness and safety of use in this group of patients.

Interaction

Antihypertensive effect of the drug Lortenza® may be enhanced when used simultaneously with other hypotensive agents. Therefore, the simultaneous use of different hypotensive agents should be justified.

Amlodipine

The concomitant use of amlodipine with thiazide diuretics, alpha-adrenoblockers or ACE inhibitors is considered safe.

Unlike other BMCCs, no clinically significant interaction of amlodipine (generation III BMCCs) has been found when used concomitantly with nonsteroidal anti-inflammatory drugs (NSAIDs), including indometacin.

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-adrenoblockers, neuroleptics.

Concomitant use of amlodipine with CYP3A4 isoenzyme inhibitors requires careful monitoring of symptoms of arterial hypotension and peripheral edema. Concomitant use of diltiazem at a dose of 180 mg daily and amlodipine at a dose of 5 mg daily in elderly patients increases the systemic exposure of amlodipine by 60%. Eritromycin concomitant use increases Cmax of amlodipine in plasma in younger patients by 22% and by 50% in elderly patients. In contrast, powerful isoenzyme inhibitorsCYP3A4 (ketoconazole, itraconazole, ritonavir) may increase the plasma concentration of amlodipine even more.

With concomitant use of inducers isoenzyme CYP3A4, plasma concentrations of amlodipine may vary. Therefore, BP control and dose adjustment of the drugs taken should be performed both during and after concomitant use, especially in combination with powerfulpowerfulinducers of CYP3A4 isoenzyme (e.g.,Rifampicin,Guarrow preparations).

Beta-adrenoblockers when used concomitantly with amlodipine may cause exacerbation of CHF.

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

A single administration of 100 mg of sildenafil in patients with AH has no effect on the pharmacokinetic parameters of amlodipine. When amlodipine was taken simultaneously with sildenafil, each drug had its own antihypertensive effect independently.

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 (drinks containing alcohol): amlodipine at a single and repeated use in a dose of 10 mg does not affect pharmacokinetics of ethanol.

Neuroleptics and isoflurane enhance the antihypertensive effects of dihydropyridine derivatives.

Intravenous administration of dantrolene with amlodipine therapy may cause collapse, arrhythmias, reduced heart rate and hyperkalemia.

The calcium drugs may decrease the antihypertensive effects of BMCCs.

When concomitant use of amlodipine with the drugs lithium may increase manifestations of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

It has no effect on the serum digoxin concentration 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 has no effect on amlodipine pharmacokinetics.

In studies under in vitro amlodipine does not affect the binding to plasma proteins of digoxin, phenytoin, warfarin and indomethacin.

The simultaneous administration of 240 mggrapefruit juice and 10 mg amlodipine orally is not accompanied by significant changes in amlodipine pharmacokinetics.

A single administration of aluminum- or magnesium-containing antacids has no significant effect on amlodipine pharmacokinetics.

When concomitantly used with amlodipine, there is a risk of increased plasma tacrolimus concentrations, but the pharmacokinetic mechanism of this interaction is not fully understood. To prevent toxic effects of tacrolimus when used concomitantly with amlodipine, plasma tacrolimus concentrations should be monitored and the dose should be adjusted if necessary.

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

Inhibitors of the mechanistic target for rapamycin in mammals (mTOR:) mTOR inhibitors, such as sirolimus, temsirolimus and everolimus, are substrates of the CYP3A isoenzyme. Amlodipine is a weak inhibitor of CYP3A isoenzyme. When used concomitantly with inhibitorsmTOR amlodipine may increase their exposure.

Drug interaction studies using cyclosporin and amlodipine in healthy volunteers or other patient groups have not been performed, except for kidney transplant patients who have had variable minimum concentrations (mean values: 0-40%) of cyclosporin. Concomitant use of amlodipine with cyclosporin may increase plasma concentrations of cyclosporin. When concomitant use of amlodipine in patients who have undergone kidney transplantation, plasma concentrations of cyclosporin 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 orwarfarin.

Simultaneous repeated use of amlodipine at a dose of 10 mg and simvastatin at a dose of 80 mg results in a 77% increase in simvastatin exposure. The dose of simvastatin when used concomitantly with amlodipine should not exceed 20 mg once daily.

Lozartan

As with other agents that block angiotensin II formation and its effects, the simultaneous use of caliberating diuretics (e.g.,

Special Instructions

Bilateral renal artery stenosis or stenosis of the artery of a single kidney, post kidney transplantation (no experience of use), coronary heart disease (CHD), heart failure with life-threatening arrhythmias, cerebrovascular disease, primary hyperaldosteronism, history of angioedema, unstable angina pectoris, use in patients with low circulating blood volume (CBC) (e.g., when using high doses of diuretics, severe diarrhea, vomiting and other conditions leading to hypovolemia) – symptomatic hypotension may occur, in patients on a diet with restriction of table salt, hyperkalemia, arterial hypotension, liver failure (less than 9 points by Child-Pugh scale), sinus node weakness syndrome (marked bradycardia, tachycardia), heart failure with concomitant severe renal dysfunction, severe CHF of non-ischemic etiology (functional class III-IV by NYHA classification), aortic and/or mitral stenosis, hypertrophic obstructive cardiomyopathy (HICMP), acute myocardial infarction (and within 1 month after the infarction), concomitant use with CYP3A4 inhibitors and inducers, electrolyte-water balance disorders, renal failure (mild and moderate degree), use in elderly patients.

The drug Lortenza® should not be used in children and adolescents under 18 years of age because there are no data about effectiveness and safety in this group of patients.

Kidney function disorder

Dose adjustment is not required for CK of 50 to 20 ml/min.

The drug Lortenza® is contraindicated in patients with CK less than 20 ml/min and in patients on hemodialysis.

Liver function disorder

Patients with a history of liver dysfunction (less than 9 points on the Child-Pugh score) are recommended to use lower doses of losartan. Due to the absence of a Lortenza® dosage containing 25 mg losartan, this dose should be administered in losartan monotherapy.

The use of the drug Lortenza® is possible in patients with impaired liver function (less than 9 points by Child-Pugh score) for whom the use of losartan in a dose of 50 mg has been recommended by a physician.

Elderly patients

In elderly patients (>65 years) due to decreased clearance, therapy with amlodipine should be started with a 2.5 mg dose once daily. Since Lortenza® has no dosage containing 2.5 mg amlodipine, this dose should be administered in amlodipine monotherapy.

Patients with decreased CPR or severe aortic stenosis

65 years). In elderly patients, due to decreased clearance resulting in an increase in the AUC of amlodipine by approximately 40-60%, amlodipine therapy is usually recommended to start with a dose of 2.5 mg once daily. Since Lortenza® does not have a dose containing 2.5 mg amlodipine, this dose should be administered in amlodipine monotherapy.

Special information about excipients

The drug Lortenza® contains lactose, so it should not be used in the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Cautions should be taken when driving vehicles and operating other technical devices requiring high concentration and quick psychomotor reactions, taking into account the risk of dizziness.

Synopsis

Tablets 5 mg + 50 mg:

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

Breakage appearance: a rough mass consisting of two layers – white or nearly white and pale yellow in color with light brown-orange film coating.

Tablets 5 mg + 100 mg:

Oval, biconvex, film-coated tablets in pink.

Breakage appearance: a rough mass consisting of two layers – white or almost white and pale yellow with a pink film coating.

Tablets 10 mg + 50 mg:

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

Break appearance: a rough mass consisting of two layers – white or almost white and pale yellow with a red-brown film coating.

Tablets 10 mg + 100 mg:

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

Fracture appearance: a rough mass consisting of two layers – white or almost white and pale yellow with a film coating of pale brownish-yellow color.

Features

Amlodipine

Amlodipine is slowly and almost completely absorbed from the gastrointestinal tract after oral administration. Simultaneous intake of food has no effect on absorption of amlodipine. Cmax in plasma is reached 6-12 hours after intake. Mean absolute bioavailability is 64-80%. The mean Vd is 21 L/kg body weight, indicating that most of the amlodipine is in the tissues and less is in the blood. Most of the amlodipine in the blood (97.5%) is bound to plasma proteins. Css in blood plasma are reached after 7-8 days of continuous amlodipine administration. Amlodipine penetrates through the HEB and the placental barrier.

Amlodipine undergoes slow but active metabolism in the liver with no significant “first pass” effect through the liver. Metabolites have no significant pharmacological activity.

After a single dose of amlodipine, the T1/2 ranges from 35 to 50 h, with a repeat use of approximately 45 h. About 60% of the oral dose is excreted by the kidneys mainly as metabolites, 10% – unchanged, 20-25% – through the intestine with the bile. Total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg). Amlodipine is not eliminated by hemodialysis.

The prolongation of T1/2 in patients with hepatic impairment suggests that amlodipine cumulation in the body will be higher with long-term use (increases to 60 h).

Lozartan

Lozartan is well absorbed after oral administration. The systemic bioavailability of losartan when ingested is approximately 33%. Cmax of losartan and its active metabolite in plasma are reached after 1 h and 3-4 h, respectively. Losartan and its active metabolite are 99% bound to plasma proteins (mainly to albumin). Vd of losartan is 34 l. The pharmacokinetics of losartan and its active metabolite are linear when administered orally in doses up to 200 mg. When administered at a dose of 100 mg once daily, neither losartan nor its active metabolite cumulate in plasma.

Lozartan is metabolized by “first pass” through the liver to form the active carboxylated metabolite (E-3174) and other inactive metabolites. Approximately 14% of the dose of losartan administered by injection or ingestion is converted to its active metabolite. After oral or intravenous administration of radioactive carbon-labeled potassium losartan (14C losartan), most of the radioactive labeling in the bloodstream was consistent with losartan and its active metabolite. Minimal biotransformation of losartan to its active metabolite was observed in approximately 1% of patients participating in clinical trials.

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 is 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 the active metabolite.

On oral administration, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final T1/2 of approximately 2 h and 6-9 h, respectively. Losartan and its metabolites are excreted by the kidneys and through the intestine with the bile. When administered orally and intravenously, 14C losartan in humans was excreted about 35% and 43%, respectively, of losartan and its active metabolite by the kidneys and 58% and 50%, respectively, through the intestine.

Plasma concentrations of losartan in women with AH were twice as high as in men with AH. In patients with mild and moderate alcoholic cirrhosis, oral administration of losartan increased plasma concentrations of losartan and its active metabolite by 5 and 1.7-fold, respectively, compared with those in young healthy male volunteers.

The AUC of losartan in patients on hemodialysis was approximately 2-fold higher compared to the AUC of losartan in patients with normal renal function. Losartan and its active metabolite are not excreted by hemodialysis.

Contraindications

– Hypersensitivity to active ingredients and/or excipients of the drug.

– Pregnancy and breastfeeding (see “Use in pregnancy and breastfeeding”).

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

– Left ventricular outflow tract obstruction (for example, hemodynamically pronounced aortic stenosis).

-Hemodynamically unstable heart failure after acute myocardial infarction.

– Shock (including cardiogenic shock).

– Age under 18 (effectiveness and safety not established).

– Severe arterial hypotension (systolic BP less than 90 mm Hg).

– Severe renal function impairment (CK less than 20 ml/min), use in patients on hemodialysis.

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

Overdose

There are no known cases of overdose with the fixed amlodipine/ losartan combination. Below are data on overdose of amlodipine and losartan taken separately.

Pregnancy use

Pregnancy

The use of Lortense® is contraindicated in pregnancy; if pregnant, the drug should be stopped immediately.

Drugs (drugs) that affect the RAAS can cause damage and death to the fetus and the newborn when used in pregnant women. Single cases of ACE inhibitors use during pregnancy have been described.

Similarities