LYPSTAPLUS FILM-COATED TABLET 10MG/10MG [SIN16651P]

Product Info

LYPSTAPLUS FILM-COATED TABLET 10MG/10MG

[SIN16651P]

4.1 Therapeutic indications

LYPSTAPLUS® is indicated as adjunct to diet for treatment of primary hypercholesterolemia as substitution therapy in adult patients adequately controlled with the individual substances given concurrently at the same dose level as in the fixed dose combination, but as separate products.

4.2 Posology and method of administration

Posology

The patient should be on an appropriate lipid-lowering diet and should continue on this diet during treatment with LYPSTAPLUS®.

The recommended daily dose is one film-coated tablet, with or without food.

LYPSTAPLUS® is not suitable for initial therapy. Treatment initiation or dose adjustment if necessary should only be done with the monocomponents and after setting the appropriate doses the switch to the fixed dose combination of the appropriate strength is possible.

LYPSTAPLUS® 10 mg/10 mg is not suitable for the treatment of patients requiring 20 mg dose of rosuvastatin.

LYPSTAPLUS® should be taken either ≥2 hours before or ≥4 hours after administration of a bile acid sequestrant.

Paediatric population
The safety and efficacy of LYPSTAPLUS® in children below the age of 18 years has not yet been established. Currently available data are described in section 4.8, 5.1 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information but no recommendation on a posology can be made.

Use in the elderly
A start dose of 5 mg rosuvastatin is recommended in patients >65 years (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The combination is not suitable for initial therapy. Treatment initiation or dose adjustment if necessary should only be done with the monocomponents and after setting the appropriate doses the switch to the fixed dose combination of the appropriate strength is possible.

Dosage in patients with renal insufficiency
No dose adjustment is necessary in patients with mild to moderate renal impairment.
The recommended start dose is rosuvastatin 5 mg in patients with moderate renal impairment (creatinine clearance <60 ml/min). The fixed dose combination is not suitable for initial therapy. Monocomponent preparations should be used to start the treatment or to modify the dose.
The use of rosuvastatin in patients with severe renal impairment is contraindicated for all doses (see sections 4.3 and 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
No dosage adjustment is required in patients with mild hepatic insufficiency (Child Pugh score 5 to 6). Treatment with LYPSTAPLUS® is not recommended in patients with moderate (Child Pugh score 7 to 9) or severe (Child Pugh score >9) liver dysfunction (See sections 4.4 and 5.2. – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). LYPSTAPLUS® is contraindicated in patients with active liver disease (see section 4.3).

Race
Increased systemic exposure of rosuvastatin has been seen in Asian subjects (see sections 4.4 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The recommended start dose is rosuvastatin 5 mg for patients of Asian ancestry. The fixed dose combination is not suitable for initial therapy. Monocomponent preparations should be used to start the treatment or to modify the dose.

The physician who elects to use rosuvastatin at doses higher than 20mg should periodically re-evaluate the long-term risk/benefit of rosuvastatin for the individual patient.

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 is recommended (see Section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Dosage in patients with pre-disposing factors to myopathy
The recommended start dose is rosuvastatin 5 mg 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). The fixed dose combination is not suitable for initial therapy. Monocomponent preparations should be used to start the treatment or to modify the dose.

Concomitant therapy
Rosuvastatin is a substrate of various transporter proteins (e.g. OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) is increased when LYPSTAPLUS® 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 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 LYPSTAPLUS® therapy. In situations where co- administration of these medicinal products with LYPSTAPLUS® is unavoidable, the benefit and the risk of concurrent treatment and rosuvastatin 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).

Method of administration
For oral use.

LYPSTAPLUS® should be taken each day once at the same time of the day with or without food.

The film-coated tablet should be swallowed whole with a drink of water.

4.3 Contraindications

• hypersensitivity to the active substances (rosuvastatin, ezetimibe) or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

• active liver disease including unexplained and persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3x the upper limit of normal (ULN) (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• pregnancy, breast-feeding and women of childbearing potential not using appropriate contraceptive measures (see section 4.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• severe renal impairment (creatinine clearance <30 ml/min) (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• patients with myopathy (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Patients receiving concomitant ciclosporin (see section 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).