Roxatenz-inda, 2.5mg+8mg+20mg 30pcs

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

Indications

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 (type IIa according to the Fredrickson classification, including familial heterozygous hypercholesterolemia), mixed hypercholesterolemia (type IIb according to the Fredrickson classification) or familial homozygous hypercholesterolemia.

Pharmacological effect

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

Special instructions

Systemic connective tissue diseases (including systemic lupus erythematosus (SLE), scleroderma), immunosuppressant therapy (risk of developing neutropenia, agranulocytosis), inhibition of bone marrow hematopoiesis, reduced circulating blood volume (CBV) (taking diuretics, diet with limited salt, vomiting, diarrhea), coronary heart disease, cerebrovascular diseases, impaired liver and kidney function, renovascular hypertension, diabetes mellitus, CHF (functional class IV according to the NYHA classification), hyperuricemia (especially accompanied by gout and urate nephrolithiasis), blood pressure lability, use in elderly patients, blacks, athletes (a positive reaction is possible during doping control), hemodialysis using high-flow polyacrylonitrile membranes (for example, AN69®), before the LDL apheresis procedure, simultaneous desensitizing therapy with allergens (for example, hymenoptera venom), condition after kidney transplantation, aortic and/or mitral valve stenosis, hypertrophic obstructive cardiomyopathy (HOCM), bilateral renal artery stenosis, stenosis of the artery of a solitary kidney, simultaneous use with lithium, gold, non-steroidal anti-inflammatory drugs (NSAIDs), baclofen, corticosteroids, drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type, the presence of a risk of developing myopathy/rhabdomyolysis – renal failure, hypothyroidism, a history of hereditary muscle diseases (including family) and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption, conditions in which an increase in plasma concentrations of rosuvastatin was noted, 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 disturbances or uncontrolled convulsions, concomitant use with ezetimibe.

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

Elderly patients

In elderly patients, the standard plasma creatinine concentration should be adjusted taking into account age, weight and gender.

Before starting to take the drug, it is necessary to assess the functional activity of the kidneys and the degree of blood pressure reduction.

Renal dysfunction

In patients with severe renal failure (creatinine clearance <30 ml/min), the use of Roxatenz-inda is contraindicated.

In patients with CC <60 ml/min, individual selection of doses of the individual active components included in the Roxatenz-inda preparation is recommended (see section "Special Instructions").

In patients with CC 60 ml/min, no dose adjustment is required. During therapy, it is necessary to regularly monitor the concentration of creatinine and potassium levels in the blood serum.

Liver dysfunction

Roxatenz-inda is contraindicated in patients with severe liver failure and patients with active liver disease (see section “Contraindications”).

For moderately severe liver failure, no dose adjustment is required.

In patients with liver failure of 7 points and below on the Child-Pugh scale, no increase in systemic exposure to rosuvastatin was detected. However, in patients with liver failure of 8-9 points on the Child-Pugh scale, an increase in systemic exposure was noted (see section “Pharmacological properties. Pharmacokinetics”). In such patients, renal function should be assessed (see section “Special Instructions”).

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

The drug does not affect the ability to drive vehicles or operate machinery, but some patients may develop various individual reactions in response to a decrease in blood pressure, especially at the beginning of therapy or when other antihypertensive drugs are added to the therapy.

Studies have not been conducted to study the effect of rosuvastatin on the ability to drive vehicles and operate machinery. However, given its pharmacodynamic properties, it is unlikely that rosuvastatin could affect these abilities. When driving vehicles or working with machinery, the possibility of dizziness during treatment should be taken into account.

As a result, the ability to operate vehicles or operate machinery may be reduced.

Active ingredient

Indapamide, Perindopril, Rosuvastatin

Composition

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

Core

Active ingredients:

Indapamide 1,250 mg

Perindopril erbumine 4,000 mg

Rosuvastatin calcium 10.395 mg, equivalent to rosuvastatin 10.000 mg

Excipients: microcrystalline cellulose, type 200, low humidity, microcrystalline cellulose, type 112, crospovidone, type A, colloidal silicon dioxide, magnesium stearate

Film shell:

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

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

Core

Active ingredients:

Indapamide 1,250 mg

Perindopril erbumine 4,000 mg

Rosuvastatin calcium 20.790 mg, equivalent to rosuvastatin 20.000 mg

Excipients: microcrystalline cellulose, type 200, low humidity, microcrystalline cellulose, type 112, crospovidone, type A, colloidal silicon dioxide, magnesium stearate

Film shell:

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

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

Core

Active ingredients:

Indapamide 2,500 mg

Perindopril erbumine 8,000 mg

Rosuvastatin calcium 10.395 mg, equivalent to rosuvastatin 10.000 mg

Excipients: microcrystalline cellulose, type 200, low humidity, microcrystalline cellulose, type 112, crospovidone, type A, colloidal silicon dioxide, magnesium stearate

Film shell:

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

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

Core

Active ingredients:

Indapamide 2,500 mg

Perindopril erbumine 8,000 mg

Rosuvastatin calcium 20.790 mg, equivalent to rosuvastatin 20.000 mg

Excipients: microcrystalline cellulose, type 200, low humidity, microcrystalline cellulose, type 112, crospovidone, type A, colloidal silicon dioxide, magnesium stearate

Film shell:

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

Pregnancy

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

Pregnancy

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

There have been no controlled clinical studies on the use of ACE inhibitors in pregnant women. Limited data indicate that taking ACE inhibitors in the first trimester did not lead to fetotoxicity-related fetal malformations, but the fetotoxic effect of ACE inhibitors cannot be completely excluded.

If pregnancy is planned or occurs while taking the drug, you should immediately stop taking the drug and prescribe an alternative antihypertensive therapy that has an established safety profile when used during pregnancy.

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

If a woman took an ACE inhibitor in the second and third trimesters of pregnancy, it is recommended to conduct an ultrasound examination of the fetal kidneys and skull.

In newborns whose mothers received therapy with ACE inhibitors, arterial hypotension may occur, so newborns should be under close medical supervision (see sections “Contraindications” and “Special Instructions”).

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

Women of reproductive age should use adequate methods of contraception.

Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of HMG-CoA reductase inhibition to the fetus outweighs the benefit to the mother from using the drug during pregnancy. Limited data on reproductive toxicity have been obtained from animal studies.

If pregnancy occurs during therapy, use of the drug should be discontinued immediately.

Breastfeeding period

The use of Roxatenz-inda is contraindicated during breastfeeding.

Due to the lack of information on the use of perindopril during breastfeeding, its use is not recommended; the use of alternative drugs with an established safety profile is preferable, especially when feeding newborns or premature infants.

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

Contraindications

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

· History of angioedema (Quincke’s edema) associated with taking ACE inhibitors (see section “Special instructions”).

· Hereditary/idiopathic angioedema.

· Severe renal failure (creatinine clearance less than 30 ml/min).

· Severe liver failure (including with hepatic encephalopathy).

· Liver diseases in the active phase (including a persistent increase in the activity of “liver” transaminases and an increase in the activity of “liver” transaminases in the blood serum by more than 3 times compared to the upper limit of normal).

· Myopathy.

· Patients predisposed to the development of myotoxic complications.

· Hypokalemia.

· Simultaneous use with drugs that can cause polymorphic ventricular arrhythmia of the “pirouette” type (see section “Interaction with other drugs”).

· Concomitant use of cyclosporine.

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

· Concomitant use with angiotensin II receptor antagonists in patients with diabetic nephropathy.

· Concomitant use with neutral endopeptidase inhibitors (for example, with drugs containing sacubitril) due to the high risk of developing angioedema (see section “Interaction with other drugs”).

· Extracorporeal treatments using certain membranes with a negatively charged surface.

· Severe bilateral renal artery stenosis or renal artery stenosis of a single functioning kidney.

· Use in women of childbearing age who do not use adequate methods of contraception.

· Pregnancy, breastfeeding period.

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

· Due to the lack of sufficient clinical experience, it should not be used in patients on hemodialysis, as well as in patients with untreated heart failure in the stage of decompensation.

Overdose

Symptoms

The most likely symptom of overdose is a marked decrease in blood pressure, sometimes in combination with nausea, vomiting, convulsions, dizziness, drowsiness, confusion and oliguria, which can progress to anuria (as a result of hypovolemia). Electrolyte disturbances (hyponatremia, hypokalemia) may also occur.

Treatment

There is no special treatment in case of overdose. In case of overdose, the patient is prescribed symptomatic treatment and replacement therapy if necessary. Emergency measures are aimed at removing the drug from the gastrointestinal tract: gastric lavage and/or taking activated carbon with subsequent restoration of water and electrolyte balance. If there is a pronounced decrease in blood pressure, the patient should be placed in an elevated position of the lower extremities, and, if necessary, correct hypovolemia (for example, intravenous infusion of 0.9% sodium chloride solution). Monitoring of liver function and serum CPK activity is necessary.

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

The effectiveness of hemodialysis for rosuvastatin is unlikely.

Storage conditions

At a temperature not exceeding 25 ºС, in the original packaging (blister).

Keep out of the reach of children.

Shelf life

3 years.

Do not use the drug after the expiration date.

Manufacturer

KRKA dd Novo Mesto, Slovenia