ROSWERA FILM-COATED TABLETS 10MG [SIN16658P]

Product Info

ROSWERA FILM-COATED TABLETS 10MG

[SIN16658P]

4.1 Therapeutic indications

ROSWERA is indicated for patients with primary hypercholesterolaemia and mixed dyslipidaemia (including Fredrickson Type IIa, IIb; and heterozygous familial hypercholesterolaemia) as an adjunct to diet when response to diet and exercise is inadequate.

ROSWERA is indicated to treat patients with primary dysbetalipoproteinaemia (Fredrickson Type III hyper lipoproteinaemia) as an adjunct to diet when response to diet and exercise is inadequate.

ROSWERA reduces elevated LDL-cholesterol, total cholesterol and triglycerides and increases HDL-cholesterol, thereby enabling most patients to achieve relevant treatment guidelines. ROSWERA also lowers ApoB, nonHDL-C, VLDL-C, VLDL-TG, the LDL-C/HDL-C, total C/HDL-C, nonHDL-C/HDL-C, ApoB/ApoA-I ratios and increases ApoA-I.

ROSWERA is also indicated in patients with homozygous familial hypercholesterolaemia, either alone or as an adjunct to diet and other lipid lowering treatments (e.g. LDL apheresis).

Primary prevention of cardiovascular disease: ROSWERA is indicated in individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease based on age ≥ 50 years old in men and ≥ 60 years old in women, hsCRP ≥ 2 mg/L, and the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease, ROSWERA is indicated to:

• reduce the risk of stroke

• reduce the risk of myocardial infarction

• reduce the risk of arterial revascularization procedures

ROSWERA is indicated in children and adolescents 10 to 17 years of age as an adjunct to diet to reduce Total-C, LDL-C and ApoB levels in adolescent boys and girls, who are at least one year postmenarche, 10–17 years of age with heterozygous familial hypercholesterolaemia if after an adequate trial of diet therapy the following findings are present: LDL-C > 190 mg/dL or > 160 mg/dL and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors. Paediatric studies were conducted mainly in the non-Asian population and data on Asian children/adolescents is limited.

4.2 Posology and method of administration

The dosage of ROSWERA should be individualised according to the goal of therapy and patient response. The recommended start dose is 5 or 10 mg once daily in both statin naive patients or patients switched from another HMG CoA reductase inhibitor. The choice of starting dose should take into account the individual patient’s cholesterol level and future cardiovascular risk as well as the potential risk for adverse reactions. A dose adjustment to the next dose level can be made after 4–6 weeks, if necessary (see Pharmacodynamic properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Increasing the dose to 40 mg should be reserved for patients with severe hypercholesterolaemia at high cardiovascular risk (in particular those with familial hypercholesterolaemia), who do not achieve their treatment goal on 20 mg and should only be initiated under close specialist supervision (see Special warnings and precautions for use of the 40 mg dose – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The physician who elects to use ROSWERA at doses higher than 20 mg should periodically re-evaluate the long-term risk/benefit of ROSWERA for the individual patient. ROSWERA should be prescribed with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis (see Special warnings and precautions for use; skeletal muscle – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

ROSWERA may be given at any time of day, with or without food.

Use in Asian population

Increased plasma concentration of rosuvastatin has been observed in Asian subjects including subjects of Japanese, Chinese, Malay and Indian ancestry (see Special warnings and precautions for use & Pharmacokinetic properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Increased systemic exposure, which is considered a pre-disposing factor for myopathy, should be taken into consideration when making dose decisions for Asian patients. Initiation of ROSWERA therapy with 5 mg once daily should be considered for Asian patients. This should take into account the individual patient’s cholesterol level and future cardiovascular risk as well as the potential risk for adverse reactions. Doses exceeding 20 mg are not generally recommended and should only be considered for patients with high cardiovascular risk whose hypercholesterolaemia is not controlled with doses up to 20 mg. In rare cases where ROSWERA at doses higher than 20 mg is indicated, initiation of therapy should be under close specialist supervision. The physician who elects to use ROSWERA at doses higher than 20 mg should periodically re-evaluate the long-term risk/benefit of ROSWERA for the individual patient.

Use in children

In paediatric patients with heterozygous familial hypercholesterolemia the recommended starting dose of ROSWERA is 5 mg taken orally once daily. The ROSWERA dose should be individualized according to baseline LDL-C levels and the recommended goal of therapy. The maximum daily dose in this patient population is 10 mg. Adjustments should be made at intervals of 4 weeks or more.

The safety and efficacy of ROSWERA doses greater than 20 mg have not been studied in this population. Treatment experience in paediatric patients with heterozygous familial hypercholesterolaemia is limited to 52 weeks.

Use in the elderly

No dose adjustment is necessary.

Dosage in patients with renal insufficiency

No dose adjustment is necessary in patients with mild to moderate renal impairment.

For patients with severe renal impairment the use of ROSWERA is contraindicated (see Pharmacokinetic properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Dosage in patients with hepatic insufficiency

The usual dose range applies in patients with mild hepatic impairment [Child-Pugh scores of ≤ 7].

Increased systemic exposure to rosuvastatin has been observed in patients with moderate hepatic impairment [Child-Pugh scores of 8 or 9]. There is no experience in patients with severe hepatic impairment. ROSWERA is contraindicated in patients with active liver disease. (see Pharmacokinetic properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Genetic polymorphisms

Genotypes of SLCO1B1 (OATPIB1) c.521CC and ABCG2 (BCRP) c.421AA have been shown to be associated with an increase in rosuvastatin exposure (AUC) compared to SLCO1B1 c.521TT and ABCG2 c.421CC. For patients known to have the c.521CC or c.421AA genotype, a maximum once daily dose of 20 mg of ROSWERA is recommended (see Special warnings and precautions for use, Interactions and Pharmacokinetic properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Concomitant therapy

Rosuvastatin is a substrate of various transporter proteins (e.g. OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) is increased when ROSWERA is administered concomitantly with certain medicinal products that may increase the plasma concentration of rosuvastatin due to interactions with these transporter proteins (e.g. cyclosporin and certain protease inhibitors including combinations of ritonavir with atazanavir, lopinavir, and/or tipranavir; see Special warnings and precautions for use and Interactions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). It is recommended that prescribers consult the relevant product information when considering administration of such products together with ROSWERA. Whenever possible, alternative medications should be considered, and if necessary, consider temporarily discontinuing ROSWERA therapy. In situations where co-administration of these medicinal products with ROSWERA is unavoidable, the benefit and the risk of concurrent treatment and ROSWERA dosing adjustments should be carefully considered (see Interactions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.3 Contraindications

ROSWERA is contraindicated in patients with hypersensitivity to any component of this product.

ROSWERA is contraindicated in patients with active liver disease or unexplained, persistent elevations of serum transaminases.

ROSWERA is contraindicated during pregnancy, while breast-feeding and in women of child-bearing potential not using appropriate contraceptive measures.

ROSWERA is contraindicated in patients receiving concomitant cyclosporin.

ROSWERA is contraindicated in patients with severe renal impairment (creatinine clearance < 30 ml/min).