Roxatenz-inda, 1.25mg+4 mg+10 mg 30 pcs

combination agent (diuretic + angiotensin-converting enzyme inhibitor + HMG-CoA reductase inhibitor)

Indications

The drug Roxatenz-inda is indicated as replacement therapy in adult patients whose condition is adequately controlled by taking indapamide, perindopril and rosuvastatin in the same doses as Roxatenz-inda in the treatment of arterial hypertension and concomitant dyslipidemia: primary hypercholesterolemia (Fredrickson type IIa, including familial heterozygous hypercholesterolemia), mixed hypercholesterolemia (Fredrickson type IIb), or familial homozygous hypercholesterolemia.

Active ingredient

Composition

1 film-coated tablet, 1.25 mg + 4 mg + 10 mg contains:

nucleus

Active substances:

Indapamide 1.250 mg

Perindopril erbumin 4,000 mg

Rosuvastatin calcium 10.395 mg, equivalent to rosuvastatin 10,000 mg

Associates: microcrystalline cellulose, type 200, low moisture, microcrystalline cellulose, type 112, crospovidone, type A, colloidal silicon dioxide, magnesium stearate

Shell film:

Film-forming compound 1: polyvinyl alcohol, macrogol-3350, titanium dioxide (E171), talc, iron oxide red dye (E172), iron oxide black dye (E172), iron oxide yellow dye (E172)

1 coated tablet, 1.25 mg + 4 mg + 20 mg contains:

nucleus

Active substances:

Indapamide 1.250 mg

Perindopril erbumin 4,000 mg

Rosuvastatin calcium 20.790 mg, equivalent to rosuvastatin 20,000 mg

Associates: microcrystalline cellulose, type 200, low moisture, microcrystalline cellulose, type 112, crospovidone, type A, colloidal silicon dioxide, magnesium stearate

Shell film:

Film-forming compound 2: polyvinyl alcohol, macrogol-3350, titanium dioxide (E171), talc, iron oxide red dye (E172), iron oxide yellow dye (E172), iron oxide black dye (E172)

1 coated tablet, 2.5 mg + 8 mg + 10 mg contains:

nucleus

Active substances:

Indapamide 2.500 mg

Perindopril erbumin 8,000 mg

Rosuvastatin calcium 10.395 mg, equivalent to rosuvastatin 10,000 mg

Associates: microcrystalline cellulose, type 200, low moisture, microcrystalline cellulose, type 112, crospovidone, type A, colloidal silicon dioxide, magnesium stearate

Shell film:

film-forming compound 3: polyvinyl alcohol, macrogol-3350, titanium dioxide (E171), talc, iron oxide red dye (E172)

1 coated tablet, 2.5 mg + 8 mg + 20 mg contains:

nucleus

Active substances:

Indapamide 2.500 mg

Perindopril erbumin 8,000 mg

Rosuvastatin calcium 20.790 mg, equivalent to rosuvastatin 20,000 mg

Associates: microcrystalline cellulose, type 200, low moisture, microcrystalline cellulose, type 112, crospovidone, type A, colloidal silicon dioxide, magnesium stearate

Shell film:

Film-forming compound 4: polyvinyl alcohol, macrogol-3350, titanium dioxide (E171), talc, iron oxide yellow dye (E172), iron oxide red dye (E172), iron oxide black dye (E172)

How to take, the dosage

Orally, 1 tablet once daily, preferably in the morning, before a meal.

The fixed-dose combination drug is not suitable for initial therapy.

When switching to treatment with Roxatense-inda, adequate patient control should be achieved while taking fixed-dose monotherapies. The dose of Roxatenz-Inda should be determined by the doses of the monodrugs that are part of the fixed combination at the time of transition.

If the dosage of one of the active substances in the composition of the fixed combined preparation needs to be changed (for example, due to newly diagnosed disease, change of the patient’s condition or drug interaction), the individual selection of doses of the individual components is necessary.

Elderly patients

In elderly patients, the normal plasma creatinine concentration should be adjusted for age, weight, and gender.

Before starting the drug, renal function and the degree of BP reduction should be assessed.

Renal Function Disorder

In patients with severe renal insufficiency (CK < 30 ml/min), the use of Roxatense-inda is contraindicated.

In patients with IQ < 60 ml/min, individual selection of doses of individual active ingredients of Roxatenz-inda is recommended (see section “Special Indications”).

In patients with CK of 60 ml/min, no dose adjustment is required. Creatinine and potassium serum concentrations should be monitored regularly during the therapy.

Liver function disorder

The drug Roxatense-inda is contraindicated in patients with severe liver failure and patients with liver disease in the active phase (see “Contraindications”).

Dose adjustment is not required in moderately severe liver failure.

In patients with hepatic failure score 7 or lower on the Child-Pugh scale no increase in systemic exposure to rosuvastatin was found. However, in patients with hepatic insufficiency with a Child-Pugh score of 8-9, an increase in systemic exposure has been noted (see section “Pharmacological properties. Pharmacokinetics”). Renal function should be evaluated in such patients (see section “Special Precautions”).

There is no experience with rosuvastatin in patients with liver failure above 9 points on the Child-Pugh scale.

Ethnic groups

Increased systemic exposure of rosuvastatin has been noted in Mongoloid patients (see Sections “Contraindications”, “Special Indications”, “Pharmacological properties. Pharmacokinetics”).

Genetic polymorphism

Certain types of genetic polymorphisms may result in increased rosuvastatin exposure (see section “Pharmacological properties. Pharmacokinetics”). Patients with these types of polymorphisms are recommended to use lower daily doses of rosuvastatin.

Companion therapy

Rosuvastatin binds to various transport proteins (particularly OATP1B1 and BCRP). When concomitant use of rosuvastatin with some drugs (such as cyclosporine, some human immunodeficiency virus (HIV) protease inhibitors, including the combination of ritonavir with atazanavir, lopinavir and/or tipranavir) that increase the plasma concentration of rosuvastatin through interaction with transport proteins, the risk of myopathy (including rhabdomyolysis) may be increased. In such cases, the possibility of alternative therapy or temporary discontinuation of rosuvastatin should be assessed. If it is necessary to use the above mentioned drugs, the benefit-risk ratio of concomitant therapy with rosuvastatin should be assessed and the possibility of its dose adjustment should be considered (see sections “Interaction with other medicinal products”, “Cautions”).

Children

The safety and effectiveness of Roxatenz-inda in children and adolescents under 18 years has not been established. The use of the drug Roxatenz-Inda is contraindicated in patients under 18 years of age.

Special Instructions

Systemic connective tissue diseases (including systemic lupus erythematosus (SLE), scleroderma), immunosuppressant therapy (risk of neutropenia, agranulocytosis), inhibition of bone marrow hematopoiesis, reduced circulating blood volume (CBC) (taking diuretics, diet with restriction of table salt, vomiting, diarrhea), coronary heart disease, cerebrovascular disease, liver and kidney function disorders, Renovascular hypertension, diabetes mellitus, CHF (functional class IV according to NYHA classification), hyperuricaemia (especially accompanied with gout and urate nephrolithiasis), labile BP, use in elderly patients, non-graceful race, athletes (possible positive reaction in doping control), hemodialysis with high-flow polyacrylonitrile membranes (for example, AN69®)strong>®), prior to LDL apheresis procedure, concomitant desensitization therapy with allergens (e.g., hymenopteran venom), post kidney transplant condition, aortic and/or mitral valve stenosis, hypertrophic obstructive cardiomyopathy (HOCMP), bilateral renal artery stenosis, single renal artery stenosis, concomitant use with lithium drugs, gold Non-steroidal anti-inflammatory drugs (NSAIDs), baclofen, corticosteroids, drugs that can cause pirouette-type polymorphic ventricular tachycardia, risk of myopathy/rhabdomyolysis – renal failure, hypothyroidism, a history of hereditary muscle disease (including family history) and a prior history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption, conditions with increased plasma concentrations of rosuvastatin, race (mongoloid race – Japanese and Chinese), concomitant use with fibrates, history of liver disease, sepsis, arterial hypotension, major surgery, trauma, severe metabolic, endocrine or electrolyte disorders or uncontrolled seizures, concomitant use with ezetimibe.

The safety and effectiveness of Roxatenz-Inda in children and adolescents under 18 years of age has not been established. The use of Roxatenz-Inda is contraindicated in patients under 18 years of age.

Elderly patients

In elderly patients, the normal plasma creatinine concentration should be adjusted for age, weight, and gender.

Before starting the drug, renal function and the degree of BP reduction should be assessed.

Renal Function Disorder

In patients with severe renal insufficiency (CK < 30 ml/min), the use of Roxatense-inda is contraindicated.

In patients with IQ < 60 ml/min, individual selection of doses of individual active ingredients of Roxatenz-inda is recommended (see section “Special Indications”).

In patients with CK of 60 ml/min, no dose adjustment is required. Creatinine and potassium serum concentrations should be monitored regularly during the therapy.

Liver function disorder

The drug Roxatense-inda is contraindicated in patients with severe liver failure and patients with liver disease in the active phase (see “Contraindications”).

Dose adjustment is not required in moderately severe liver failure.

In patients with hepatic failure score 7 or lower on the Child-Pugh scale no increase in systemic exposure to rosuvastatin was found. However, in patients with hepatic insufficiency with a Child-Pugh score of 8-9, an increase in systemic exposure has been noted (see section “Pharmacological properties. Pharmacokinetics”). Renal function should be evaluated in these patients (see section “Cautions”).

There is no experience with rosuvastatin in patients with liver failure above 9 points on the Child-Pugh scale.

The drug does not affect the ability to drive vehicles and operate machinery, but some patients may develop various individual reactions in response to BP reduction, especially at the beginning of therapy or when adding other hypotensive agents to the current therapy.

Studies on the effect of rosuvastatin on driving and operating machinery have not been conducted. However, given the pharmacodynamic properties, it is unlikely that rosuvastatin may affect these abilities. When driving vehicles or working with mechanisms the possibility of dizziness during treatment should be considered.

As a result, the ability to operate vehicles or other mechanisms may be impaired.

Synopsis

Tablets 1.25 mg + 4 mg + 10 mg:

Circular, slightly biconvex, film-coated, reddish brown tablets with PIR1 engraved on one side and beveled.

Tablets 1.25 mg + 4 mg + 20 mg:

Circular, slightly biconvex, film-coated tablets in pink with a grayish tint, with PIR2 engraving on one side and a bevel.

Tablets 2.5 mg + 8 mg + 10 mg:

Round, slightly biconvex, film-coated pale pink tablets, with PIR3 engraving on one side and bevel.

Tablets 2.5 mg + 8 mg + 20 mg:

Circular, slightly biconvex, film-coated pale pinkish-brown tablets, with PIR4 engraving on one side and bevel.

Contraindications

– Hypersensitivity to indapamide and – other sulfonamide derivatives, perindopril and other ACE inhibitors, rosuvastatin or any other component of the drug.

– Angioneurotic edema (Quincke’s edema) in the anamnesis associated with the use of ACE inhibitors (see section “Cautions”).

– Hereditary/idiopathic angioedema.

– Severe renal failure (CK less than 30 ml/min).

– Severe liver failure (including liver encephalopathy).

– Liver diseases in the active phase (including a persistent increase in “hepatic” transaminase activity and an increase in “hepatic” transaminase activity in serum more than 3 times the upper limit of normal).

– Myopathy.

– Patients prone to developing myotoxic complications.

– Hypokalemia.

– Simultaneous use with drugs that can cause pirouette-type polymorphic ventricular arrhythmias (see section “Interaction with other medicinal products”).

– Concurrent administration of cyclosporine.

– Concurrent use with aliskiren or drugs containing aliskiren in patients with diabetes mellitus and/or moderate to severe renal function impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 body surface area).

– Concurrent use with angiotensin II receptor antagonists in patients with diabetic nephropathy.

– Concomitant use with neutral endopeptidase inhibitors (e.g., with drugs containing sacubitril) due to the high risk of angioedema (see section “Interaction with other medicinal products”).

– Extracorporeal treatments using some negatively charged membranes.

– Severe bilateral renal artery stenosis or renal artery stenosis of the only functioning kidney.

– Use in women of childbearing age who are not using adequate contraception.

– Pregnancy, breast-feeding.

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

– Due to insufficient clinical experience, should not be used in patients on hemodialysis or in patients with untreated decompensated heart failure.

Overdose

Symptoms

The most likely symptom of overdose is a marked decrease in blood pressure, sometimes combined with nausea, vomiting, seizures, dizziness, drowsiness, confusion and oliguria, which may progress to anuria (due to hypovolemia). Electrolyte disorders may also occur (hyponatremia, hypokalemia).

treatment

There is no special treatment in case of overdose. In case of overdose the patient is shown symptomatic treatment and substitution therapy if necessary. Emergency measures are aimed at the removal of the drug from the gastrointestinal tract: gastric lavage and/or intake of activated charcoal, followed by restoration of water-electrolyte balance. In case of marked BP decrease the patient should be laid with elevated position of the lower extremities, if necessary, correction of hypovolemia should be performed (e.g., intravenous infusion of 0.9% sodium chloride solution). It is necessary to monitor the liver function and serum CPK activity.

Perindoprilat, the active metabolite of perindopril, is removed by hemodialysis.

The effectiveness of hemodialysis for rosuvastatin is unlikely.

Pregnancy use

The use of the drug Roxatenz-inda is contraindicated in pregnancy and during breastfeeding.

Pregnancy

The use of ACE inhibitors is not recommended during the I trimester of pregnancy. The use of ACE inhibitors is contraindicated during the second and third trimesters of pregnancy.

There are no controlled clinical studies on the use of ACE inhibitors in pregnant women. Limited data suggest that ACE inhibitors use in the first trimester has not resulted in fetotoxicity-related fetal malformations, but fetotoxic effects of ACE inhibitors cannot be completely excluded.

If pregnancy is planned or if pregnancy occurs while taking the drug, the drug should be immediately stopped and an alternative hypotensive therapy with an established safety profile for use during pregnancy should be indicated.

It is known that the use of ACE inhibitors in the second and third trimesters of pregnancy can lead to impaired fetal development (reduced renal function, oligohydramnion, delayed ossification of the skull bones) and development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

If a woman was taking ACE inhibitor in the second and third trimesters of pregnancy, an ultrasound examination of the fetal kidneys and skull is recommended.

Newborns whose mothers received ACE inhibitor therapy may be hypotensive, so newborns should be under close medical supervision (see

Sections “Contraindications” and “Special Precautions”).

Long-term use of thiazide diuretics in the third trimester of pregnancy may cause hypovolemia in mother and decrease uteroplacental blood flow, which leads to fetoplacental ischemia and delayed fetal development. In rare cases hypoglycemia and thrombocytopenia have been observed in the newborns while taking diuretics.

Women of reproductive age should use adequate contraception.

Because cholesterol and cholesterol-synthesized substances are important for fetal development, the potential risk of HMG-CoA reductase inhibition to the fetus exceeds the benefits of the drug in pregnancy to the mother. There have been limited data on reproductive toxicity in animal studies.

If pregnancy occurs during therapy, the drug should be stopped immediately.

Breastfeeding period

The use of the drug Roxatense-inda is contraindicated during breastfeeding.

In the absence of information about the use of perindopril during breastfeeding, its administration is not recommended; alternative drugs with an established safety profile are preferred, especially when feeding newborns or premature infants.

Indapamide is excreted with breast milk. Administration of thiazide diuretics causes a decrease in the amount of breast milk or suppression of lactation. The newborn may develop hypersensitivity to sulfonamide derivatives, hypokalemia and “nuclear” jaundice.

Rosuvastatin is excreted in milk in rats. There are no data on excretion of rosuvastatin into breast milk in humans.