ALVOSTAT FILM COATED TABLETS 20MG [SIN14997P]

Product Info

ALVOSTAT FILM COATED TABLETS 20MG

[SIN14997P]

4.1 Therapeutic indications

Treatment of hypercholesterolaemia

Adults with primary hypercholesterolaemia (type IIa) or mixed dyslipidaemia (type IIb) as an adjunct to diet when response to diet and other non-pharmacological treatments (e.g. exercise, weight reduction) is inadequate.

Homozygous familial hypercholesterolaemia as an adjunct to diet and other lipid lowering treatments (e.g. LDL apheresis) or if such treatments are not appropriate.

Prevention of Cardiovascular Events

Primary prevention of cardiovascular disease: ALVOSTAT 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 ALVOSTAT is indicated to:

• reduce the risk of stroke

• reduce the risk of myocardial infarction

• reduce the risk of arterial revascularization procedures

4.2 Posology and method of administration

Before treatment initiation the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment. The dose should be individualised according to the goal of therapy and patient response, using current consensus guidelines.

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

Treatment of hypercholesterolaemia
The recommended start dose is 5 or 10 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 4–6 weeks, if necessary (see Section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). In light of the increased reporting rate of adverse reactions with the 40 mg dose compared to lower doses (see Section 4.8 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), 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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Specialist supervision is recommended when the 40 mg dose is initiated.

Paediatric use
ALVOSTAT is not indicated for use in children.

Use in the elderly
No dose adjustment is necessary in relation to age.

Dosage in patients with renal insufficiency
No dose adjustment is necessary in patients with mild to moderate renal impairment.
The use of ALVOSTAT in patients with severe renal impairment is contraindicated for all doses. (See Section 4.3 and Section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Dosage in patients with hepatic impairment
There was no increase in systemic exposure to rosuvastatin in subjects with mild hepatic impairment (Child-Pugh scores of 7 or below) and the usual dose range applies in such patients. However, increased systemic exposure has been observed in subjects with moderate hepatic impairment (Child-Pugh scores of 8 and 9) (see Section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). In these patients an assessment of renal function should be considered (see Section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). There is no experience in subjects with severe hepatic impairment (Child-Pugh scores above 9). ALVOSTAT is contraindicated in patients with active liver disease (see Section 4.3).

Race
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 ALVOSTAT 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 ALVOSTAT at doses higher than 20 mg is indicated, initiation of therapy should be under close specialist supervision. The physician who elects to use ALVOSTAT at doses higher than 20 mg should periodically re-evaluate the long-term risk/benefit of ALVOSTAT for the individual patient.

Dosage in patients with predisposing factors to myopathy
ALVOSTAT should be prescribed with caution in patients with predisposing factors to myopathy (see Section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Genetic polymorphisms
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 ALVOSTAT is recommended (see Sections 4.4, 4.5 and 5.2 – 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 ALVOSTAT 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 Sections 4.4 and 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Whenever possible, alternative medications should be considered, and if necessary, consider temporarily discontinuing ALVOSTAT therapy. In situations where co-administration of these medicinal products with ALVOSTAT is unavoidable, the benefit and the risk of concurrent treatment and ALVOSTAT dosing adjustments should be carefully considered (see Section 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.3 Contraindications
ALVOSTAT is contraindicated:

• in patients with hypersensitivity to rosuvastatin or to any of the excipients.

• in patients with active liver disease including unexplained, persistent elevations of serum transaminases.

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

• in patients receiving concomitant ciclosporin.

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