Crestor - Art 29 Paed - CHMP Opinion

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Annex I

List of the names, pharmaceutical forms, strengths of the medicinal products, route of administration and marketing authorisation holders in the Member States

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Member State EU/EEA

Marketing authorisation holder

company name, address

(Invented) Name

Strength Pharmaceutical form Route of administration

Austria AstraZeneca Österreich GmbH, Schwarzenbergplatz 7, A-1037 Wien, Austria

Crestor 5 mg – Filmtabletten

5 mg

Film coated tablets Oral use



10 mg




20 mg




40 mg Film coated tablets Oral use

Belgium NV AstraZeneca SA Egide Van Ophemstraat 110 B-1180 Brussels, Belgium

Crestor 5 mg



Crestor 10 mg



Crestor 20 mg


3

Member State EU/EEA



(Invented) Name



Crestor 40 mg Film coated tablets Oral use

Bulgaria AstraZeneca Pharmaceuticals AB, S-151 85 Södertälje, Sweden

Crestor 5 mg



Crestor 10 mg




Croatia AstraZeneca d.o.o. Radnička cesta 80 10000 Zagreb Croatia

Crestor 5 mg filmom obložene tablete

5 mg


Croatia

AstraZeneca d.o.o. Radnička cesta 80 10000 Zagreb Croatia


10 mg


4

Member State EU/EEA



(Invented) Name




20 mg




40 mg


Cyprus AstraZeneca UK Limited, 2 Kingdom Street, London W2 6BD, United Kingdom

Crestor 5 mg



Crestor 10 mg



Crestor 20 mg




5

Member State EU/EEA



(Invented) Name


Czech Republic

AstraZeneca UK Limited, 2 Kingdom Street London W2 6BD United Kingdom

Crestor 5 mg 5 mg Film coated tablets Oral use

Czech Republic



Czech Republic



Czech Republic



Denmark AstraZeneca A/S Arne Jacobsens Allé 13 2300 København S Denmark

Crestor 5 mg



Crestor 10 mg


6

Member State EU/EEA



(Invented) Name



Crestor 20 mg




Estonia AstraZeneca UK Ltd. 2 Kingdom Street, London W2 6BD, United Kingdom

Crestor 5 mg



Crestor 10 mg




Finland AstraZeneca Oy Itsehallintokuja 4 02600 Espoo Finland

Crestor 5 mg


7

Member State EU/EEA



(Invented) Name



Crestor 10 mg



Crestor 20 mg




France AstraZeneca 1, Place Renault 92844 Rueil-Malmaison Cedex, France

Crestor 5 mg



Crestor 10 mg




Germany AstraZeneca GmbH, 22876 Wedel, Germany

CRESTOR 5 mg Filmtabletten

5 mg


8

Member State EU/EEA



(Invented) Name




10 mg




20 mg





Greece AstraZeneca SA 4 Theotokopoulou & Astronafton str 151 25 Maroussi, Athens Greece

Crestor 5 mg



Crestor 10 mg



Crestor 20 mg




9

Member State EU/EEA



(Invented) Name


Hungary

AstraZeneca Kft., 1113 Budapest, Bocskai út 134-146., Hungary

Crestor 5 mg filmtabletta

5 mg


Hungary



10 mg


Hungary




Iceland

AstraZeneca A/S Arne Jacobsens Allé 13 2300 København S Denmark

Crestor 5 mg


Iceland


Crestor 10 mg


Iceland


Crestor 20 mg


10

Member State EU/EEA



(Invented) Name


Iceland



Ireland

AstraZeneca UK Limited, 600 Capability Green, Luton, LU1 3LU, United Kingdom

Crestor 5 mg


Ireland


Crestor 10 mg


Ireland


Crestor 20 mg


Ireland



Italy

AstraZeneca S.p.A. Palazzo Volta, Via F. Sforza 20080 Basiglio (MI), Italy

Crestor 5 mg


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Member State EU/EEA



(Invented) Name


Italy


Crestor 10 mg


Italy


Crestor 20 mg


Italy



Italy


Cirantan 5 mg


Italy


Cirantan 10 mg


Italy


Cirantan 20 mg


12

Member State EU/EEA



(Invented) Name


Italy


Cirantan 40 mg Film coated tablets Oral use

Italy


Provisacor 5 mg


Italy


Provisacor 10 mg


Italy


Provisacor 20 mg


Italy


Provisacor 40 mg Film coated tablets Oral use

Italy

Simesa S.P.A. Palazzo Galileo, Via F. Sforza, 20080 Basiglio (MI), Italy

Simestat 5 mg


13

Member State EU/EEA



(Invented) Name


Italy


Simestat 10 mg


Italy


Simestat 20 mg Film coated tablets Oral use

Italy


Simestat 40 mg Film coated tablets Oral use

Latvia

AstraZeneca UK Limited 2 Kingdom Street London W2 6BD United Kingdom

Crestor 5 mg apvalkotās tabletes

5 mg


Latvia



10 mg


Latvia



20 mg


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Member State EU/EEA



(Invented) Name


Latvia




Lithuania


Crestor 5 mg


Lithuania


Crestor 10 mg


Lithuania


Crestor 20 mg


Lithuania



Luxembourg

NV AstraZeneca SA Egide Van Ophemstraat 110 B-1180 Brussels, Belgium

Crestor 5 mg


15

Member State EU/EEA



(Invented) Name


Luxembourg


Crestor 10 mg


Luxembourg


Crestor 20 mg


Luxembourg



Malta


Crestor 5 mg


Malta


Crestor 10 mg


Malta


Crestor 20 mg


16

Member State EU/EEA



(Invented) Name


Malta



The Netherlands

AstraZeneca BV Louis Pasteurlaan 5 2719 EE Zoetermeer The Netherlands

Crestor 5 mg


The Netherlands


Crestor 10 mg


The Netherlands


Crestor 20 mg


The Netherlands



The Netherlands


Cirantan 5 mg


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Member State EU/EEA



(Invented) Name


The Netherlands


Cirantan 10 mg


The Netherlands


Cirantan 20 mg


The Netherlands


Cirantan 40 mg Film coated tablets Oral use

The Netherlands



The Netherlands


Provisacor 10 mg


The Netherlands


Provisacor 20 mg


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Member State EU/EEA



(Invented) Name


The Netherlands



The Netherlands


Rosuvastatin AstraZeneca

5 mg


The Netherlands



10 mg


The Netherlands



20 mg


The Netherlands




Norway

AstraZeneca AS Postboks 6050, Etterstad 0601 Oslo Norway

Crestor 5 mg


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Member State EU/EEA



(Invented) Name


Norway


Crestor 10 mg


Norway


Crestor 20 mg


Norway



Poland

AstraZeneca AB, S-151 85 Södertälje, Sweden

Crestor 5 mg


Poland


Crestor 10 mg


Poland


Crestor 20 mg


Poland



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Member State EU/EEA



(Invented) Name


Portugal

AstraZeneca Produtos Farmacêuticos, Lda. Rua Humberto Madeira, 7 Queluz de Baixo 2730-097 Barcarena Portugal

Crestor 5 mg 5 mg


Portugal


Crestor 10 mg 10 mg


Portugal


Crestor 20 mg 20 mg


Portugal



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Member State EU/EEA



(Invented) Name


Portugal

AstraZeneca Produtos Farmacêuticos, Lda. Rua Humberto Madeira, 7, Queluz de Baixo 2730-097 Barcarena Portugal

Visacor 5 mg 5 mg


Portugal


Visacor 10 mg 10 mg


Portugal


Visacor 20 mg 20 mg


Portugal


Visacor 40 mg 40 mg Film coated tablets Oral use

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Member State EU/EEA



(Invented) Name


Romania

AstraZeneca UK Limited 2 Kingdom Street, London W2 6BD, United Kingdom

Crestor 5 mg comprimate filmate

5 mg


Romania



10 mg


Romania



20 mg


Romania




Slovak Republic

AstraZeneca UK Ltd 2 Kingdom Street London, W2 6BD, United Kingdom

CRESTOR 5 mg 5 mg


Slovak Republic


CRESTOR 10 mg 10 mg


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Member State EU/EEA



(Invented) Name


Slovak Republic


CRESTOR 20 mg 20 mg


Slovak Republic


CRESTOR 40 mg 40mg Film coated tablets Oral use

Slovenia

AstraZeneca UK Limited 2 Kingdom Street London, W2 6BD, United Kingdom

Crestor 5 mg filmsko obložene tablete

5 mg


Slovenia



10 mg


Slovenia



20 mg


Slovenia




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Member State EU/EEA



(Invented) Name


Spain

AstraZeneca Farmacéutica Spain, S.A. Parque Norte.Edificio Roble. C/ Serrano Galvache 56, 28033 Madrid, Spain.

Crestor 5 mg comprimidos recubiertos con película

5 mg


Spain



10 mg


Spain



20 mg


Spain




Spain


Provisacor 5 mg comprimidos recubiertos con película

5 mg


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Member State EU/EEA



(Invented) Name


Spain



10 mg


Spain



20 mg


Spain




Sweden

AstraZeneca AB, S-151 85 Södertälje Sweden

Crestor 5 mg


Sweden


Crestor 10 mg


Sweden


Crestor 20 mg


Sweden



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Member State EU/EEA



(Invented) Name


United Kingdom


Crestor 5 mg


United Kingdom


Crestor 10 mg


United Kingdom


Crestor 20 mg


United Kingdom



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Annex II

Amendments to the Summary of Product Characteristics and Package Leaflet

This Summary of Product Characteristics and package leaflet is the outcome of the referral procedure and valid at the time of the Commission Decision.

The product information may be subsequently updated by the Member State competent authorities, in liaison with the Reference Member State, as appropriate, in accordance with the procedures laid down in Chapter 4 of Title III of Directive 2001/83/EC.

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AMENDMENTS TO BE INCLUDED IN THE RELEVANT SECTIONS OF THE SUMMARY OF PRODUCT CHARACTERISTICS FOR CRESTOR AND ASSOCIATED NAMES

4. CLINICAL PARTICULARS

4.1 Therapeutic indications [The wording of the indication for treatment of hypercholesterolaemia should be replaced with the following:]

Treatment of hypercholesterolaemia Adults, adolescents and children aged 6 years or older with primary hypercholesterolaemia (type IIa including heterozygous familial hypercholesterolaemia) 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.

4.2 Posology and method of administration [Existing information on the paediatric population should be replaced with the following:]

Paediatric population Paediatric use should only be carried out by specialists. Children and adolescents 6 to 17 years of age (Tanner Stage <II-V) In children and adolescents with heterozygous familial hypercholesterolaemia the usual start dose is 5 mg daily. • In children 6 to 9 years of age with heterozygous familial hypercholesterolaemia, the usual dose

range is 5-10 mg orally once daily. Safety and efficacy of doses greater than 10 mg have not been studied in this population.

• In children 10 to 17 years of age with heterozygous familial hypercholesterolaemia, the usual dose range is 5-20 mg orally once daily. Safety and efficacy of doses greater than 20 mg have not been studied in this population.

Titration should be conducted according to the individual response and tolerability in paediatric patients, as recommended by the paediatric treatment recommendations (see Section 4.4). Children and adolescents should be placed on standard cholesterol-lowering diet before rosuvastatin treatment initiation; this diet should be continued during rosuvastatin treatment. Experience in children with homozygous familial hypercholesterolaemia is limited to a small number of children aged between 8 and 17 years. The 40 mg tablet is not suitable for use in paediatric patients. Children younger than 6 years The safety and efficacy of use in children younger than 6 years has not been studied. Therefore, Crestor is not recommended for use in children younger than 6 years.

4.4 Special warnings and precautions for use [Existing information on the paediatric population should be replaced with the following:] Paediatric population The evaluation of linear growth (height), weight, BMI (body mass index), and secondary characteristics of sexual maturation by Tanner staging in paediatric patients 6 to 17 years of age taking rosuvastatin

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is limited to a two-year period. After two years of study treatment, no effect on growth, weight, BMI or sexual maturation was detected (see Section 5.1). In a clinical trial of children and adolescents receiving rosuvastatin for 52 weeks, CK elevations >10xULN and muscle symptoms following exercise or increased physical activity were observed more frequently compared to observations in clinical trials in adults (see Section 4.8).

5.1 Pharmacodynamic properties [Existing information on the paediatric population should be replaced with the following:] Paediatric population In a double-blind, randomized, multi-centre, placebo-controlled, 12-week study (n=176, 97 male and 79 female) followed by a 40-week (n=173, 96 male and 77 female), open-label, rosuvastatin dose-titration phase, patients 10-17 years of age (Tanner stage II-V, females at least 1 year post-menarche) with heterozygous familial hypercholesterolaemia received rosuvastatin 5, 10 or 20 mg or placebo daily for 12 weeks and then all received rosuvastatin daily for 40 weeks. At study entry, approximately 30% of the patients were 10-13 years and approximately 17%, 18%, 40%, and 25% were Tanner stage II, III, IV, and V, respectively. LDL-C was reduced 38.3%, 44.6%, and 50.0% by rosuvastatin 5, 10 and 20 mg, respectively, compared to 0.7% for placebo. At the end of the 40-week, open-label, titration to goal, dosing up to a maximum of 20 mg once daily, 70 of 173 patients (40.5%) had achieved the LDL-C goal of less than 2.8 mmol/l. After 52 weeks of study treatment, no effect on growth, weight, BMI or sexual maturation was detected (see Section 4.4). This trial (n=176) was not suited for comparison of rare adverse drug events. Rosuvastatin was also studied in a 2-year open-label, titration-to-goal study in 198 children with heterozygous familial hypercholesterolaemia aged 6 to 17 years (88 male and 110 female, Tanner stage <II-V). The starting dose for all patients was 5 mg rosuvastatin once daily. Patients aged 6 to 9 years (n=64) could titrate to a maximum dose of 10 mg once daily and patients aged 10 to 17 years (n=134) to a maximum dose of 20 mg once daily. After 24 months of treatment with rosuvastatin, the LS mean percent reduction from the baseline value in LDL-C was -43% (Baseline: 236 mg/dL, Month 24: 133 mg/dL). For each age group, the LS mean percent reductions from baseline values in LDL-C were -43% (Baseline: 234 mg/dL, Month 24: 124 mg/dL), -45% (Baseline: 234 mg/dL, 124 mg/dL ), and -35% (Baseline: 241 mg/dL, Month 24: 153 mg/dL) in the 6 to <10, 10 to <14, and 14 to <18 age groups, respectively. Rosuvastatin 5 mg, 10 mg, and 20 mg also achieved statistically significant mean changes from baseline for the following secondary lipid and lipoprotein variables: HDL-C, TC, non-HDL-C,LDL-C/HDL-C, TC/HDL-C, TG/HDL-C, non HDL C/HDL-C, ApoB, ApoB/ApoA-1. These changes were each in the direction of improved lipid responses and were sustained over 2 years. No effect on growth, weight, BMI or sexual maturation was detected after 24 months of treatment (see Section 4.4). The European Medicines Agency has waived the obligation to submit the results of studies with rosuvastatin in all subsets of the paediatric population in the treatment of homozygous familial hypercholesterolaemia, primary combined (mixed) dyslipidaemia and in the prevention of cardiovascular events (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties [Existing information on the paediatric population should be replaced with the following:] Paediatric population: Two pharmacokinetic studies with rosuvastatin (given as tablets) in paediatric patients with heterozygous familial hypercholesterolaemia 10-17 or 6-17 years of age (total of 214

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patients) demonstrated that exposure in paediatric patients appears comparable to or lower than that in adult patients. Rosuvastatin exposure was predictable with respect to dose and time over a 2-year period.

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AMENDMENTS TO BE INCLUDED IN THE RELEVANT SECTIONS OF THE PACKAGE LEAFLET FOR CRESTOR AND ASSOCIATED NAMES

1. What CRESTOR is and what it is used for [Existing wording of this section should be replaced with the following:]

CRESTOR belongs to a group of medicines called statins. You have been prescribed CRESTOR because:

• You have a high cholesterol level. This means you are at risk from a heart attack or stroke. Crestor is used in adults, adolescents and children 6 years or older to treat high cholesterol.

You have been advised to take a statin, because changing your diet and taking more exercise were not enough to correct your cholesterol levels. You should continue with your cholesterol-lowering diet and exercise while you are taking CRESTOR. Or

• You have other factors that increase your risk of having a heart attack, stroke or related health problems.

2. What you need to know before you take CRESTOR

[Existing information on the paediatric population should be replaced with the following:]

Children and adolescents

• If the patient is under 6 years old: CRESTOR should not be given to children younger than 6 years.

• If the patient is below 18 years of age: The CRESTOR 40 mg tablet is not suitable for use in children and adolescents below 18 years of age.

3. How to take CRESTOR [Existing information on the paediatric population should be replaced with the following:]

Use in children and adolescents aged 6–17 years

The usual start dose is 5 mg. Your doctor may increase your dose to find the right amount of CRESTOR for you. The maximum daily dose of CRESTOR is 10 mg for children aged 6 to 9 years and 20 mg for children aged 10 to 17 years. Take your dose once a day. CRESTOR 40 mg tablet should not be used by children.

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Annex III

Conditions of the marketing authorisations

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National Competent Authorities (NCAs), coordinated by the Reference Member State where applicable, shall ensure that the following conditions are fulfilled by the Marketing Authorisation Holders (MAHs): An updated version of the Risk Management Plan will be submitted to National Competent Authorities within 3 months of the Commission Decision for this procedure, to reflect the updated information on the paediatric population as agreed by CHMP.

Documents

Crestor - Art 29 Paed - CHMP Opinion