ZUVAMOR Film-coated tablet Ref.[108837] Active ingredients: Rosuvastatin

Posology

Before treatment initiation, the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment.

Treatment of hypercholesterolaemia

The recommended start dose is 5 mg orally once daily in both statin naïve or patients switched from another HMG CoA reductase inhibitor. The choice of start dose should take into account the individual patient’s cholesterol level and future cardiovascular risk as well as the potential risk for adverse reactions (see below). A dose adjustment to the next dose level can be made after 4 weeks, if necessary (see section 5.1). In light of the increased reporting rate of adverse reactions with the 40 mg dose compared to lower doses (see section 4.8), a final titration to the maximum dose of 40 mg should only be considered in 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 in whom routine follow-up will be performed (see section 4.4). Specialist supervision is recommended when the 40 mg dose is initiated.

The dosage of ZUVAMOR should be individualised according to the goal of therapy and patient response. The majority of patients are controlled at the 10 mg dose. However, if necessary, dose adjustment can be made at 4 week intervals (see section 5.1).

Adults

Primary hypercholesterolaemia (including heterozygous familial hypercholesterolaemia), mixed dyslipidaemia, dysbetalipoproteinaemia (Fredrickson Type III hyperlipoproteinaemia) and isolated hypertriglyceridaemia

The recommended start dose is 5 mg once a day.

For patients with severe hypercholesterolaemia (including heterozygous familial hypercholesterolaemia), a start dose of 20 mg may be considered.

Homozygous familial hypercholesterolaemia

For patients with homozygous familial hypercholesterolaemia a start dose of 20 mg once a day is recommended.

Special populations

Use in the elderly

The usual dose range applies.

Dosage in patients with renal insufficiency

No dose adjustment is necessary in patients with mild to moderate renal impairment. The recommended start dose is 5 mg in patients with moderate renal impairment (creatinine clearance <60 ml/min). The 40 mg dose is contraindicated in patients with moderate renal impairment. The use of ZUVAMOR in patients with severe renal impairment is contraindicated for all doses (see sections 4.3 and 5.2).

Dosage in patients with hepatic insufficiency

There was no increase in systemic exposure to rosuvastatin in subjects with Child-Pugh scores of 7 or below. The usual starting dose applies in patients with mild to moderate hepatic impairment. However, increased systemic exposure has been observed in subjects with Child-Pugh scores of 8 and 9 (see section 5.2). In these patients an assessment of renal function should be considered (see section 4.4). There is no experience in subjects with Child-Pugh scores above 9. Patients with severe hepatic impairment should start therapy with ZUVAMOR 5 mg. Increased systemic exposure to rosuvastatin has been observed in these patients, therefore the use of doses above ZUVAMOR 10 mg should be carefully considered (see section 5.2). ZUVAMOR is contraindicated in patients with active liver disease (see section 4.3).

Race

A 5 mg starting dose of ZUVAMOR should be considered for Asian patients. Increased plasma concentration of rosuvastatin has been seen in Asian subjects (see section 4.4 and 5.2). The increased systemic exposure should be taken into consideration when treating Asian patients whose hypercholesterolaemia is not adequately controlled at doses up to 20 mg daily. The 40 mg dose is contraindicated in these patients.

Genotypes of SLCO1B1 (OATP1B1) 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 ZUVAMOR should not be exceeded (see section 4.4, 4.5 and 5.2).

Concomitant therapy

Rosuvastatin is a substrate of various transporter proteins (e.g. OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) is increased when ZUVAMOR is administered concomitantly with certain medicinal products that may increase the plasma concentration of rosuvastatin due to interactions with these transporter proteins (e.g. ciclosporin and certain protease inhibitors including combinations of ritonavir with atazanavir, lopinavir, and/or tipranavir (see section 4.4 & 4.5).

It is recommended that prescribers consult the relevant product information when considering administration of such products together with ZUVAMOR. Whenever possible, alternative medications should be considered, and if necessary, consider temporarily discontinuing ZUVAMOR therapy. In situations where co-administration of these medicinal products with ZUVAMOR is unavoidable, the benefit and the risk of concurrent treatment and ZUVAMOR dosing adjustments should be carefully considered (see section 4.4).

Paediatric population

Children and adolescents 10-17 years of age

In children and adolescents with heterozygous familial hypercholesterolaemia the usual dose range is 5-20 mg orally once daily. The dose should be appropriately titrated to achieve treatment goal. Safety and efficacy of doses greater than 20 mg have not been studied in this population.

In children and adolescents with homozygous familial hypercholesterolaemia, experience is limited to a small number of patients (aged 8 years and above).

Method of administration

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

There is no specific treatment in the event of overdose. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required. Liver function and CK levels should be monitored. Haemodialysis is unlikely to be of benefit.

ZUVAMOR 5: 36 months.

ZUVAMOR 10: 24 months.

ZUVAMOR 20: 24 months.

ZUVAMOR 40: 24 months.

Blister packs: Store at or below 30°C. Keep the blister in the carton until required for use.

HDPE bottles: Store at or below 30°C. Keep container tightly closed.

ZUVAMOR 5 mg, 10 mg, 20 mg and 40 mg tablets:

Aluminium laminate/aluminium foil blister packs of 28 or 30 tablets.

ZUVAMOR 5 mg, 10 mg, 20 mg and 40 mg tablets:

HDPE bottles: bottles containing 30, 90 or 100 tablets.

No special requirements.