qanastek/EMEA-V3 huggingface dataset:
If you miss a dose, just resume your usual schedule the following day.
Se dovesse dimenticare una dose, il giorno seguente si limiti a riprendere il Suo schema di dosaggio abituale.
Do not take a double dose to make up for the forgotten tablet.
Non prenda una dose doppia per compensare la compressa che ha dimenticato.
Like all medicines ,< ARCOXIA > can cause side effects, although not everybody gets them.
Come tutti i medicinali < ARCOXIA > può causare effetti collaterali, che tuttavia non si verificano in tutti i pazienti.
If you develop any of these signs you should stop< ARCOXIA > and talk to your doctor immediately: • shortness of breath, chest pains, or ankle swelling appear or if they get worse • yellowing of the skin and eyes (jaundice) – these are signs of liver problems • severe or continual stomach pain or your stools become black • an allergic reaction- which can include skin problems such as ulcers or blistering, or swelling of the face, lips, tongue, or throat which may cause difficulty in breathing
• respiro affannoso, dolori toracici, o gonfiore delle caviglie che insorgono o iniziano a peggiorare • colorazione gialla della cute e degli occhi (ittero)-questi sono sintomi di problemi di fegato • dolore di stomaco grave o continuo o feci che diventano nere • una reazione allergica che può comprendere problemi cutanei come ulcere o formazione di vescicole, o gonfiore di faccia, labbra, lingua, o gola che può rendere difficoltosa la respirazione.
The following side effects can occur during treatment with< ARCOXIA >:
Nel corso del trattamento con < ARCOXIA > possono manifestarsi i seguenti effetti collaterali:
Common (occurring in greater than 1 out of 100 and less than 1 out of 10 people) Weakness and fatigue, dizziness, headache, flu-like illness, diarrhoea, wind, nausea, indigestion (dyspepsia), stomach pain or discomfort, heartburn, changes in blood tests related to your liver, swelling of the legs and/ or feet due to fluid retention (oedema), increased blood pressure, palpitations, bruising.
Comuni (si verificano in più di una persona su 100 e in meno di 1 su 10) Debolezza e affaticamento, capogiro, mal di testa, malattia simil-influenzale, diarrea, flatulenza, nausea, problemi di digestione (dispepsia), disturbi gastrointestinali come dolore o fastidio allo stomaco, bruciore alla bocca dello stomaco, alterazioni di alcuni esami del sangue legati alla funzione del fegato, gonfiore delle gambe e/o dei piedi dovuto a ritenzione di liquidi (edema), aumento della pressione sanguigna, palpitazioni, comparsa di lividi.
Uncommon (occurring in greater than 1 out of 1000 and less than 1 out of 100 people) Stomach or bowel bloating, chest pain, heart failure, heart attack, stroke, mini-stroke (transient ischaemic attack), abnormal heart rhythm (atrial fibrillation), upper respiratory infection, high levels of potassium in your blood, changes in blood or urine tests relating to your kidney, changes in your bowel habits including constipation, dry mouth, mouth ulcers, taste alteration, gastroenteritis, gastritis, stomach ulcer, being sick (vomiting), irritable bowel syndrome, inflammation of the esophagus, blurred vision, eye irritation and redness, nose bleed, ringing in the ears, vertigo, appetite increases or decreases, weight gain, muscle cramp/ spasm, muscle pain/ stiffness, inability to sleep, sleepiness, numbness or tingling, anxiety, depression, 37 decreases in mental sharpness, breathlessness, cough, swelling of the face, flushing, skin rash or itchy skin, urinary tract infection.
Non comuni (si verificano in più di una persona su 1.000 e in meno di 1 su 100) Gonfiore di stomaco o d'intestino, dolore toracico, insufficienza cardiaca, attacco di cuore, ictus, mini-ictus (attacco ischemico transitorio), anormalità del battito cardiaco (fibrillazione atriale), infezione della parte alta dell'apparato respiratorio, livelli elevati di potassio nel sangue, alterazione di alcuni esami del sangue e delle urine legati alla funzionalità del rene, cambiamenti delle abitudini intestinali inclusa la stitichezza, bocca secca, ulcere della bocca, alterazione del gusto, gastroenterite, gastrite, ulcera dello stomaco, conati di vomito (vomito), sindrome del colon irritabile, infiammazione dell'esofago, visione offuscata, irritazione e arrossamento degli occhi, sangue dal naso, ronzio alle orecchie, vertigine, aumenti o diminuzioni dell’appetito, aumento di peso, crampi/spasmi muscolari, dolore/rigidità muscolare, difficoltà a dormire, sonnolenza, formicolio o intorpidimento, ansia, depressione, diminuzione dell’acutezza mentale, difficoltà a respirare, tosse, gonfiore della faccia, vampate, eruzione della pelle o prurito della pelle, infezione del tratto urinario.
Rare (occurring in greater than 1 out of 10,000 and less than 1 out of 1000 people) Low blood levels of sodium.
Rari (si verificano in più di una persona su 10.000 e in meno di 1 su 1.000) Bassi livelli di sodio nel sangue.
Very Rare (occurring in less than 1 out of 10,000 people) Allergic reactions (which may be serious enough to require immediate medical attention) including hives, swelling of the face, lips, tongue, and/ or throat which may cause difficulty in breathing or swallowing, bronchospasm (wheezing or shortness of breath), severe skin reactions, inflammation of the stomach lining or stomach ulcers that can become serious and may lead to bleeding, liver problems, serious kidney problems, severe increase in blood pressure, confusion, seeing, feeling or hearing things that are not there (hallucinations).
Molto rari (si verificano in meno di 1 persona su 10.000) Reazioni allergiche (che possono essere abbastanza serie da richiedere l’intervento immediato del medico) inclusa orticaria, gonfiore del viso, delle labbra, della lingua e/o della gola che può causare difficoltà a respirare e ad inghiottire, broncospasmo (respiro sibilante o respiro corto), reazioni cutanee gravi, infiammazione della superficie interna dello stomaco o ulcere dello stomaco, che possono diventare serie e possono sanguinare, problemi epatici, seri problemi renali, grave aumento della pressione sanguigna, confusione mentale, percezioni visive, sensitive o uditive non provocate da stimoli reali (allucinazioni).
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Se uno qualsiasi degli effetti collaterali peggiora, o se nota la comparsa di un qualsiasi effetto indesiderato non elencato in questo foglio, informi il medico o il farmacista.
HOW TO STORE< ARCOXIA >
COME CONSERVARE < ARCOXIA >
Do not use< ARCOXIA > after the expiry date which is stated on the pack.
Non prendere < ARCOXIA > dopo la data di scadenza indicata sulla confezione.
The expiry date refers to the last day of the month.
La data di scadenza si riferisce all'ultimo giorno del mese indicato.
Keep the container tightly closed in order to protect from moisture.
39 Flacone: tenere il contenitore ben chiuso per proteggere il medicinale dall'umidità.
Store in the original package in order to protect from moisture.
Blister: conservare nella confezione originale per proteggere il medicinale dall'umidità.
What< ARCOXIA > contains
Cosa contiene < ARCOXIA >
• The active substance is etoricoxib.
• La sostanza attiva è l'etoricoxib.
Each film coated tablet contains 30, 60, 90 or 120 mg of etoricoxib.
Ciascuna compressa rivestita con film contiene 30, 60, 90 o 120 mg di etoricoxib.
• The other ingredients are:
• Gli altri componenti sono:
Core: calcium hydrogen phosphate (anhydrous), croscarmellose sodium, magnesium stearate, microcrystalline cellulose.
Interno delle compresse: calcio fosfato dibasico anidro, croscarmellosa sodica, magnesio stearato, cellulosa microcristallina.
Tablet coating: carnauba wax, lactose monohydrate, hypromellose, titanium dioxide (E171), triacetin.
Rivestimento delle compresse: cera carnauba, lattosio monoidrato, ipromellosa, titanio diossido (E171), triacetina.
The 30-, 60- and 120-mg tablets also contain yellow ferric oxide (E172, colouring agent) and indigo carmine lake (E132, colouring agent).
Le compresse da 30, 60 e 120 mg contengono anche ferro ossido giallo (colorante E172) e indigotina lacca (colorante E132).
What< ARCOXIA > looks like and contents of the pack
Come si presenta < ARCOXIA > e cosa contiene la confezione
< ARCOXIA > Tablets are available in four strengths:
Le compresse di < ARCOXIA > sono disponibili in quattro formulazioni:
30 mg blue-green, apple-shaped, biconvex film coated tablets marked ‘ ACX 30’ on one side and ‘ 101’ on the other.
compresse da 30 mg biconvesse, a forma di mela, di colore verde blu, con inciso ‘ACX 30’ su un lato e ‘101’ sull’altro.
38 60 mg dark green, apple-shaped, biconvex film coated tablets marked ‘ ARCOXIA 60’ on one side and ‘ 200’ on the other.
compresse da 60 mg, biconvesse, a forma di mela, di colore verde scuro, con inciso ‘ARCOXIA 60’ su un lato e ‘200’ sull’altro;
90 mg white, apple-shaped, biconvex film coated tablets marked ‘ ARCOXIA 90’ on one side and ‘ 202’ on the other.
compresse da 90 mg, biconvesse, a forma di mela, di colore bianco, con inciso ‘ARCOXIA 90’ su un lato e ‘202’ sull’altro;
120 mg pale-green, apple-shaped, biconvex film coated tablets marked ‘ ARCOXIA 120’ on one side and ‘ 204’ on the other.
compresse da 120 mg, biconvesse, a forma di mela, di colore verde chiaro, con inciso ‘ARCOXIA 120’ su un lato e ‘204’ sull’altro.
Pack sizes of 7 and 28 tablets in blisters.
Confezioni da 7 e 28 compresse in blister.
60, 90, 120 mg:
60, 90 e 120 mg:
Pack sizes of 2, 5, 7, 10, 14, 20, 28, 30, 50, 84, 98 or 100 tablets in blisters; or 30 and 90 tablets in bottles.
Confezioni da 2, 5, 7, 10, 14, 20, 28, 30, 50, 84, 98 or 100 compresse in blister; o 30 e 90 compresse in flaconi.
Marketing Authorisation Holder and Manufacturer [See Annex 1-To be filled in nationally] {Name and address} {tel} {fax} {e-mail}
[Vedere Allegato 1 - Completare con i dati nazionali] {Nome e indirizzo} {tel} {fax} {e-mail}
This medicinal product is authorized in the Member States of the EEA under the following names:
40 Questo prodotto medicinale è autorizzato in altri paesi membri dell'EEA con i seguenti nomi:
Austria Belgium Bulgaria Czech Rep.
Austria Belgio Bulgaria Rep.Ceca Cipro Danimarca Estonia Finlandia
Cyprus Denmark Estonia Finland France Germany Greece Hungary Iceland Ireland Italy Latvia Lithuania Luxembourg Malta Netherlands Norway Poland Portugal Romania Slovakia Slovenia Spain
Francia Germania Grecia Hungheria Islanda Irlanda Italia Lettonia Lituania Lusemburgo Malta Paesi Bassi Norvegia Polonia Portogallo
Arcoxia 30 mg, 60 mg, 90 mg, 120 mg-Filmtabletten Arcoxia 30 mg, 60 mg, 90 mg, 120 mg, comprimés pelliculés ARCOXIA ARCOXIA 30 mg, 60 mg, 90 mg, 120 mg Arcoxia 30, 60, 90, 120 mg Arcoxia Arcoxia Arcoxia 30, 60, 90 ja 120 mg tabletti, kalvopäällysteinen Arcoxia 30 mg, comprimé pelliculé ARCOXIA 30/ 60/ 90/ 120 mg Filmtabletten ARCOXIA 30mg, 60mg, 90mg,120mg film-coated tablets Arcoxia 30 mg, 60 mg, 90 mg, 120 mg filmtabletta Arcoxia Arcoxia 30, 60, 90 or 120 mg film-coated tablets Arcoxia 30, 60, 90, 120 mg compresse rivestite con film Arcoxia 30 mg, 60 mg, 90 mg un 120 mg apvalkotā s tablets Arcoxia 30, 60, 90, 120 mg plė vele dengtos tabletė s Arcoxia 30 mg, 60 mg, 90 mg, 120 mg, comprimés pelliculés ARCOXIA 30, 60, 90 or 120 mg film-coated tablets Arcoxia 30 mg, 60 mg, 90 mg, 120 mg Arcoxia ARCOXIA 30 mg, 60 mg, 90 mg, 120 mg tabletki powlekane ARCOXIA 30 mg, 60 mg, 90 mg, 120 mg comprimidos revestidos por película ARCOXIA 60 mg, 90 mg, 120 mg, comprimate filmate ARCOXIA 30 mg, 60 mg, 90 mg, 120 mg Arcoxia 30/ 60/ 90/ 120 mg filmsko oblož ene tablete Arcoxia 30, 60, 90 y 120 mg comprimidos recubiertos con película
Arcoxia 30 mg, comprimé pelliculé ARCOXIA 30/60/90/120 mg Filmtabletten ARCOXIA 30mg, 60mg, 90mg,120mg compresse rivestite con film Arcoxia 30 mg, 60 mg, 90 mg, 120 mg filmtabletta Arcoxia Arcoxia 30, 60, 90 or 120 mg compresse rivestite con film Arcoxia 30, 60, 90, 120 mg compresse rivestite con film Arcoxia 30 mg, 60 mg, 90 mg un 120 mg apvalkotās tablets Arcoxia 30, 60, 90, 120 mg plėvele dengtos tabletės Arcoxia 30 mg, 60 mg, 90 mg, 120 mg, comprimés pelliculés ARCOXIA 30, 60, 90 or 120 mg compresse rivestite con film Arcoxia 30 mg, 60 mg, 90 mg, 120 mg Arcoxia ARCOXIA 30 mg, 60 mg, 90 mg, 120 mg tabletki powlekane ARCOXIA 30 mg, 60 mg, 90 mg, 120 mg comprimidos revestidos por película
Sweden United Kingdom
Romania Slovacchia Slovenia Spagna Svezia Regno Unito
Arcoxia 30 mg, 60 mg, 90 mg och 120 mg filmdragerade tabletter ARCOXIA 30, 60, 90 or 120 mg film-coated tablets
ARCOXIA 60 mg, 90 mg, 120 mg, comprimate filmate ARCOXIA 30 mg, 60 mg, 90 mg, 120 mg Arcoxia 30/60/90/120 mg filmsko obložene tablete Arcoxia 30, 60, 90 y 120 mg comprimidos recubiertos con película Arcoxia 30 mg, 60 mg, 90 mg och 120 mg filmdragerade tabletter ARCOXIA 30, 60, 90 or 120 mg compresse rivestite con film
This leaflet was last approved in (MM/ YYYY).
Questo foglio illustrativo è stato approvato l’ultima volta il (MM/AAAA).
41 CONDITIONS OF THE MARKETING AUTHORISATION
41 ALLEGATO IV
who prescribe etoricoxib according to national practice.
CONDIZIONI DELL’AUTORIZZAZIONE ALL’IMMISSIONE IN COMMERCIO
42
42 CONDIZIONI DELL’AUTORIZZAZIONE ALL’IMMISSIONE IN COMMERCIO
London, 23 October 2008 EMEA/ 438258/ 2008
Londra, 23 ottobre 2008 EMEA/ CHMP/ 619559/ 2008
COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) OPINION FOLLOWING AN ARTICLE 6 (12) REFERRAL
PARERE DEL COMITATO PER I MEDICINALI PER USO UMANO (CHMP) SU UN DEFERIMENTO AI SENSI DELL’ ARTICOLO 6, PARAGRAFO 12
International non-proprietary name (INN): etoricoxib
Denominazione comune internazionale (DCI): etoricoxib
BACKGROUND INFORMATION *
INFORMAZIONI GENERALI*
Etoricoxib is a selective inhibitor of COX-2 (cyclooxygenase 2) indicated in the symptomatic relief of osteoarthritis (OA, 30-60mg once daily (od)), rheumatoid arthritis (RA, 90mg od) and the pain and signs of inflammation associated with acute gouty arthritis (120mg od).
Etoricoxib è un inibitore selettivo di COX-2 (cicloossigenasi 2) indicato nel trattamento sintomatico della osteoartrite (OA, 30-60 mg una volta al giorno), dell’ artrite reumatoide (RA, 90 mg una volta al giorno), e del dolore e dei segni dell’ infiammazione associata all’ artrite gottosa acuta (120 mg una volta al giorno).
This referral procedure relates to a request for arbitration concerning a type II variation for a new indication to include treatment of ankylosing spondylitis (AS), at a recommended daily dose of 90mg.
La presente procedura di deferimento si riferisce ad una richiesta per arbitrato relativa ad una variazione di tipo II per una nuova indicazione al fine di includere il trattamento della spondilite anchilosante ad una dose giornaliera consigliata di 90 mg.
At the end of the mutual recognition procedure, there was a discrepancy between different European Union (EU) Member States regarding the safety of etoricoxib at the 90mg dose in the new proposed indication.
Al termine della procedura di mutuo riconoscimento, diversi Stati membri dell’ Unione europea si sono trovati in disaccordo riguardo alla sicurezza di etoricoxib alla dose di 90 mg nella nuova indicazione proposta.
As these concerns were not resolved during the course of the procedure, a notification of an official referral for arbitration under Article 6(12) of Commission Regulation EC No 1084/ 2003 to the CHMP was made by France on 19 September 2007.
1084/ 2003 della Commissione.
The main unresolved areas of concern identified by France were concerns regarding long term safety of a daily dose of 90mg etoricoxib in the view of possible increased cardiovascular (CV) risk related to the use of the 90mg dose in the ankylosing spondylitis (AS) indication.
Le principali aree di preoccupazione irrisolte identificate dalla Francia si riferivano alla sicurezza di lungo termine di una dose giornaliera di 90 mg di etoricoxib alla luce di un possibile aumento del rischio cardiovascolare correlato all’ uso della dose di 90 mg nell’ indicazione della spondilite anchilosante.
France considered that a review of the benefit/ risk profile of Arcoxia was needed.
La Francia ha ritenuto che fosse necessario un riesame del profilo beneficio/ rischio di Arcoxia.
The arbitration procedure was discussed by the CHMP at its plenary meeting in September 2007 and a Rapporteur (Dr.
La procedura di arbitrato è stata discussa dal CHMP nella riunione plenaria del settembre 2007 con la nomina di un relatore (dott.
Karl Broich) and Co-Rapporteur (Dr.
Karl Broich) e di un correlatore (dott.
The referral procedure was initiated on 20 September 2007 with the adoption of a CHMP list of questions that were to be addressed by the marketing authorisation holders (MAHs).
La procedura di deferimento è iniziata il 20 settembre 2007 con l’ adozione di un elenco di domande poste dal CHMP che dovevano essere rivolte al titolare dell’ autorizzazione all’ immissione in commercio.
During the February 2008 plenary meeting Dr.
Durante la riunione plenaria del febbraio 2008 il dott.
Rafe Survana was appointed Co-Rapporteur, replacing Dr.
Rafe Survana è stato nominato correlatore, in sostituzione del dott.
Written explanations were provided by the MAHs on 14 December 2008, 5 May 2008, 12 June 2008 and 20 June 2008.
Chiarimenti sono stati forniti per iscritto dal titolare dell’ autorizzazione all’ immissione in commercio in data 14 dicembre 2007, 5 maggio 2008, 12 giugno 2008 e 20 giugno 2008.
The CHMP concluded that the data confirmed the known renovascular safety profile of etoricoxib (hypertension, oedema and congestive heart failure).
Il comitato per i medicinali per uso umano ha concluso che i dati confermano il profilo di sicurezza renovascolare noto di etoricoxib (ipertensione, edema ed insufficienza cardiaca congestiva).
The data further confirmed a similar CV thrombotic risk like diclofenac and some degree of upper gastrointestinal (GI) safety advantage over naproxen and diclofenac (though no particular lower GI safety advantage).
I dati hanno inoltre confermato un rischio trombotico cardiovascolare analogo a quello del diclofenac ed un certo livello di sicurezza del tratto gastrointestinale superiore rispetto a naproxen e diclofenac (ma nessun particolare vantaggio relativo alla sicurezza dell’ apparato gastrointestinale inferiore).
There was little direct comparative safety data for individual non-steroidal anti-inflammatory drugs (NSAIDs) other than diclofenac and naproxen.
Vi sono stati pochi dati di sicurezza direttamente comparabili per singoli farmaci antinfiammatori non steroidei (FANS) diversi dal diclofenac e dal naproxen.
7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel.
Era quindi difficile determinare i rischi di etoricoxib 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel.
Reproduction is authorised provided the source is acknowledged. within 2 weeks of treatment initiation.
Reproduction is authorised provided the source is acknowledged. confrontato con ibuprofen, ketoprofen od altri farmaci antinfiammatori non steroidei di uso meno comune.
Healthcare professionals were to be reminded of these measures through a communication letter (Dear Healthcare Professional Letter).
Tali misure devono essere rammentate agli operatori sanitari tramite una nota informativa (Dear Healthcare Professional Letter).
Data from clinical studies showed clinically meaningful treatment effect for the 90mg etoricoxib once daily dose for AS indication; however, some data are available to indicate that lower doses might also show effect.
I dati derivanti dagli studi clinici hanno evidenziato un effetto terapeutico clinicamente significativo per la singola dose giornaliera da 90 mg di etoricoxib per l’ indicazione della spondilite anchilosante; tuttavia, alcuni dati disponibili evidenziano che anche dosaggi più blandi potrebbero avere effetto.
The CHMP therefore recommended that dose finding studies should be explored to conclude if treatment with 60mg once daily would also be adequate for some patients.
Il comitato per i medicinali per uso umano ha quindi raccomandato un esame degli studi relativi alla determinazione del dosaggio per concludere se il trattamento con una singola dose giornaliera da 60 mg sia anche adeguato per alcuni pazienti.
Based on the review of the available data, the CHMP considered that the benefits of etoricoxib outweigh the risks in the treatment of ankylosing spondylitis.
Basandosi sull’ esame dei dati disponibili, il comitato per i medicinali per uso umano ha ritenuto che i benefici di etoricoxib sono superiori ai rischi nel trattamento della spondilite anchilosante.
On 26 June 2008, the CHMP, having considered the data provided by the MAHs, recommended the granting of the variation to the marketing authorisations.
Il 26 giugno 2008, il comitato per i medicinali per uso umano, dopo avere esaminato i dati forniti dai titolari dell’ autorizzazione all’ immissione in commercio, ha raccomandato di autorizzare la variazione dell’ autorizzazione all’ immissione in commercio.
The scientific conclusions are provided in Annex II, the amended product information in Annex III and the conditions of the marketing authorisation in Annex IV.
Le conclusioni scientifiche si trovano nell’ allegato II, le informazioni modificate sul prodotto nell’ allegato III e le condizioni dell’ autorizzazione all’ immissione in commercio nell’ allegato IV.
The final opinion was converted into a decision by the European Commission on 9 September 2008.
Il parere definitivo è stato convertito in decisione dalla Commissione europea il 9 settembre 2008.
∗ Notes: the information given in this document and its annexes reflects only the CHMP opinion dated 26 June 2008.
∗ Note: le informazioni contenute nel presente documento e negli allegati riflettono esclusivamente il parere del CHMP del 26 giugno 2008.
The Member States’ competent authorities will continue to keep the product under regular review.
Le autorità competenti degli Stati membri continueranno ad assicurare una regolare revisione del prodotto.
LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTHS OF THE MEDICINAL PRODUCTS, ROUTE OF ADMINISTRATION, MARKETING AUTHORISATION HOLDERS IN THE MEMBER STATES
ELENCO DEI NOMI, DELLA FORMA FARMACEUTICA, DEI DOSAGGI, DELLA VIA DI SOMMINISTRAZIONE, DEI RICHIEDENTI, DEI TITOLARI DELL’ AUTORIZZAZIONE ALL’ IMMISSIONE IN COMMERCIO NEGLI STATI MEMBRI Stato Membro Austria
1 Member State Austria Austria Austria Austria Belgium Belgium Belgium Belgium Denmark Denmark Denmark Denmark Finland Finland Finland Finland Germany Germany Germany Germany Greece Greece
Titolare dell’ Autorizzazione all’ Immissione in Commercio Pfizer Corporation Austria Ges. m. b. H.
Pfizer Corporation Austria Ges. m. b. H.
Austria
Pfizer S. A.
Uso orale
Strength 10mg 20mg 40mg 80mg 10mg 20mg 40mg 80mg 10mg 20mg 40mg 80mg 10mg 20mg 40mg 80mg 10mg 20mg 40mg 80mg 10mg 20mg
20mg
Pharmaceutical form Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet
Compresse rivestite con film
Route of administration Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use
Uso orale
2 Member State Greece Greece Italy Italy Italy Italy Luxembourg Luxembourg Luxembourg Luxembourg Netherlands Netherlands Netherlands Netherlands Portugal Portugal Portugal Portugal Spain Spain Spain Spain
Belgio
PARKE-DAVIS, S. L.
Lipitor
PARKE-DAVIS, S. L.
Compresse rivestite con film
PARKE-DAVIS, S. L.
Uso orale
Invented name Lipitor Lipitor Xarator Xarator Xarator Xarator Lipitor Lipitor Lipitor Lipitor Lipitor Lipitor Lipitor Lipitor Zarator Zarator Zarator Zarator Zarator Zarator Zarator Zarator
Danimarca
Strength 40mg 80mg 10mg 20mg 40mg 80mg 10mg 20mg 40mg 80mg 10mg 20mg 40mg 80mg 10mg 20mg 40mg 80mg 10mg 20mg 40mg 80mg
Pfizer ApS
Pharmaceutical form Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet
Zarator
Route of administration Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use
10mg
3 Member State Sweden Sweden Sweden Sweden
Compresse rivestite con film
Marketing Authorisation Holder Pfizer AB Pfizer AB Pfizer AB Pfizer AB
Pfizer ApS
Invented name Lipitor Lipitor Lipitor Lipitor
Zarator
Strength 10mg 20mg 40mg 80mg
20mg
Pharmaceutical form Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet
Compresse rivestite con film
Route of administration Oral use Oral use Oral use Oral use
Uso orale
4 ANNEX II
Danimarca
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF ATORVASTATIN (Sortis and associated names - see Annex I)
40mg
The currently approved indications for atorvastatin are:
Compresse rivestite con film
- as an adjunct to diet for reduction of elevated total cholesterol, LDL-cholesterol, apolipoprotein
Uso orale
B, and tryglicerides in patients with primary hypercholesterolemia including familial hypercholesterolemia (heterozygous variant) or combined (mixed) hyperlipidaemia (corresponding to Types IIa and IIb of the Fredrickson classification) when response to diet and other nonpharmacological measures is inadequate.
Danimarca
Background information on the type II variation through the MRP In the initial type II variation dossier submitted by MRP, the Applicant claimed the following indication: “ Prevention of cardiovascular events in patients with multiple risk factors (e. g. type 2 diabetics with one risk factor and hypertensive patients with 3 risk factors) with normal or elevated cholesterol levels but without clinically evident coronary heart disease (CHD )”.
80mg
This wording was based on the results of 2 randomised controlled trials performed with atorvastatin 10 mg for the primary prevention of cardiovascular disease (CVD).
Compresse rivestite con film
In the Final Assessment report (1 November 2005) the Reference Member State proposed, and the MAH agreed to, the following indication: “ Prevention of cardiovascular events in patients with type 2 diabetes and one additional risk factor with normal to mildly elevated cholesterol level without clinically evident coronary heart disease”.
Uso orale
thus restricting the indication to the population included in the CARDs trial and relegating the results of the ASCOT-LLA trial to a description in section 5.1. of the SPC, based on the lack of demonstrated efficacy in the female subgroup.
Finlandia
At the end of the MRP procedure there was a discrepancy between Member States regarding the wording of the proposed indication that adequately reflects the data of the ASCOT-LLA and CARDS studies, effectively excluding treatment in non-diabetics, and an official referral for arbitration was notified by Spain to the CHMP on 1 December 2005.
Pfizer Oy
1.
Lipitor
2.
10mg
Whether the cardioprotective effect of atorvastatin is higher when used in combination with particular antihipertensive therapy(ies) and whether this should be reflected in the SPC.
Compresse rivestite con film
4.
Uso orale
5.
Finlandia
Evaluation of Clinical Efficacy
Pfizer Oy
The main issue discussed by the CHMP has been the results of the ASCOT-LLA trial, most importantly the lack of established benefit and adverse mortality trends in the female subgroup and, secondly, the impact of the observed interaction between the antihypertensive amlodipine and atorvastatin on the main trial outcomes for certain subgroups.
Lipitor
The Applicant has presented arguments for the view that the results for women in ASCOT-LLA based on subgroup analyses are most likely chance findings and are not considered scientifically robust enough to form the basis for regulatory actions.
20mg
The main concern relates to the “ risk of CVD”.
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Regarding the interaction observed between atorvastatin and amlodipine, the body of data assessed indicates that this interaction is of questionable clinical relevance, if it exists at all, and does not warrant regulatory action dictating the prescription of the product.
Uso orale
In the light of the above the CHMP concludes that the indication for atorvastatin “ Prevention of cardiovascular events in patients estimated to have a high risk for a first cardiovascular event, as an adjunct to correction of other risk factors .” adequately reflects the available data.
40mg
Overall conclusion on benefit/ risk
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Whereas, • the CHMP considered the referral made under article 6.12 of Commission Regulation (EC) No 1084/ 2003, for atorvastatin (Sortis and associated names - see Annex I), • The MAH has implemented the text proposed by the CHMP in the SPC:
80mg
- It is proposed to add the following indication in section 4.1:
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Prevention of cardiovascular events in patients estimated to have a high risk for a first cardiovascular event (see section 5.1), as an adjunct to correction of other risk factors.
Uso orale
-
Germania
In the primary prevention trials the dose was 10 mg/ day.
PARKE-DAVIS GmbH
-
Sortis
Section 5.1 has been updated to include the results of the ASCOT-LLA and CARDS trials as follows:
10mg
8 Patients were treated with anti-hypertensive therapy (either amlodipine or atenolol-based regimen) and either atorvastatin 10 mg daily (n=5168) or placebo (n=5137).
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The absolute and relative risk reduction effect of atorvastatin was as follows:
Uso orale
Relative
Germania
No. of
PARKE-DAVIS GmbH
Risk
20mg
Events
Uso orale
Risk
Germania
Reduction1
40mg
Event
Uso orale
(%)
Germania
Placebo)
PARKE-DAVIS GmbH
Fatal CHD plus non-fatal MI Total cardiovascular events
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36%
Uso orale
100 vs.
Grecia
154
Pfizer Hellas AE
0.0005
10mg
and revascularization procedures Total coronary events 1
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20% 29%
Uso orale
389 vs.
Grecia
483 178 vs 247
Pfizer Hellas AE
0.0008 0.0006
20mg
CHD = coronary heart disease; MI = myocardial infarction.
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212 events, p=0.17 and 74 vs.
Uso orale
82 events, p=0.51).
2 Stato Membro Grecia
Overall and cardiovascular mortality were numerically higher in the female patients (38 vs.
Titolare dell’ Autorizzazione all’ Immissione in Commercio Pfizer Hellas AE
30 and 17 vs.
Dosaggio 40mg
The effect of atorvastatin on fatal and non-fatal cardiovascular disease was also assessed in a randomised, double-blind, multicentre, placebo-controlled trial, the Collaborative Atorvastatin Diabetes Study (CARDS) in patients with type 2 diabetes, 40-75 years of age, without prior history of cardiovascular disease, and with LDL-C ≤ 4.14 mmol/ l (160 mg/ dl) and TG≤ 6.78 mmol/ l (600 mg/ dl).
Forma farmaceutica Compresse rivestite con film
The absolute and relative risk reduction effect of atorvastatin were as follows:
Via di somministrazione Uso orale
Relative
Grecia
No. of
Pfizer Hellas AE
Risk
Italia
Reduction
PARKE-DAVIS SpA
(Sortis vs
Xarator
Reduction1
10mg
Event Major cardiovascular events (fatal and non-fatal AMI, silent MI, acute CHD death, unstable angina, CABG, PTCA,
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(%)
Italia
Placebo)
PARKE-DAVIS SpA
(%)
Xarator
revascularisation, stroke) MI (fatal and non-fatal AMI, silent MI) Strokes (Fatal and non-fatal) 1
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37% 42% 48%
Uso orale
83 vs.
Italia
3.2% 1.9% 1.3%
PARKE-DAVIS SpA
Based on difference in crude events rates occurring over a median follow-up of 3.9 years.
40mg
61 deaths in the atorvastatin group, p=0.0592).
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• no untoward safety findings related to the extension of the indication have been identified.
Uso orale
SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
80mg
11 SUMMARY OF PRODUCT CHARACTERISTICS
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12 1.
Uso orale
NAME OF THE MEDICINAL PRODUCT
Lussemburgo
QUALITATIVE AND QUANTITATIVE COMPOSITION
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Each film-coated tablet contains 10 mg atorvastatin (as atorvastatin calcium (trihydrate)).
Uso orale
Excipients:
Lussemburgo
Each {PRODUCT NAME} 10 mg film-coated tablet contains 32.80 mg lactose monohydrate.
Pfizer S. A.
For a full list of excipients, see section 6.1.
Lipitor
PHARMACEUTICAL FORM
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Film-coated tablet White elliptical, film-coated tablets debossed "10" on one side and "PD 155" on the other.
Uso orale
CLINICAL PARTICULARS
Lussemburgo
LDL apheresis) or if such treatments are unavailable.
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Prevention of cardiovascular disease
Uso orale
Prevention of cardiovascular events in patients estimated to have a high risk for a first cardiovascular event (see section 5.1), as an adjunct to correction of other risk factors.
Lussemburgo
The maximum dose is 80 mg once a day.
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Each daily dose of atorvastatin is given all at once and may be given at any time of day with or without food.
Uso orale
13 For patients with established coronary heart disease or other patients at increased risk of ischemic events, the treatment goal is LDL-C < 3 mmol/ l (or < 115 mg/ dl) and total cholesterol < 5 mmol/ l (or < 190 mg/ dl).
Paesi Bassi
Adapted from “ Prevention of coronary heart disease in clinical practice:
Pfizer bv
Heterozygous familial hypercholesterolaemia
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Patients should be started with {PRODUCT NAME} 10 mg daily.
Uso orale
Homozygous familial hypercholesterolaemia
Paesi Bassi
In a compassionate-use study of 64 patients there were 46 patients for whom confirmed LDL receptor information was available.
Pfizer bv
Dosage in patients with renal insufficiency
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Renal disease has no influence on the atorvastatin plasma concentrations nor lipid effects of {PRODUCT NAME}; thus, no adjustment of dose is required.
Uso orale
Geriatric use
Paesi Bassi
Pediatric use should only be carried out by specialists.
40mg
4.3 Contraindications
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14 {PRODUCT NAME} is contraindicated in patients: − with hypersensitivity to the active substance or to any of the excipients of this medication − with active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal − with myopathy − during pregnancy − while breast-feeding − in women of child-bearing potential not using appropriate contraceptive measures.
Uso orale
4.4 Special warnings and precautions for use
Paesi Bassi
{PRODUCT NAME} should be used with caution in patients who consume substantial quantities of alcohol and/ or have a history of liver disease.
80mg
Skeletal muscle effects
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Atorvastatin, like other HMG-CoA reductase inhibitors, may in rare occasions affect the skeletal muscle and cause myalgia, myositis, and myopathy that may progress to rhabdomyolysis, a potentially life-threatening condition characterised by markedly elevated CPK levels (> 10 times ULN), myoglobinaemia and myoglobinuria which may lead to renal failure.
Uso orale
Before the treatment Atorvastatin should be prescribed with caution in patients with pre-disposing factors for rhabdomyolysis.
Portogallo
Whilst on treatment − Patients must be asked to promptly report muscle pain, cramps, or weakness especially if accompanied by malaise or fever.
10mg
15 − If such symptoms occur whilst a patient is receiving treatment with atorvastatin, their CPK levels should be measured.
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Risk of rhabdomyolysis is increased when atorvastatin is administered concomitantly with certain medicaments such as: ciclosporin, erythromycin, clarithromycin, itraconazole, ketoconazole, nefazodone, niacin, gemfibrozil, other fibric acid derivates or HIV-protease inhibitors (see section 4.5 and section 4.8).
Uso orale
Patients with rare hereditary problems of galactose intolerance, Lapp lactose deficiency or glucose- galactose malabsorption should not take this medicine.
Portogallo
Inhibitors of cytochrome P450 3A4
20mg
Atorvastatin is metabolized by cytochrome P450 3A4.
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Inhibitors of P-glycoprotein
Uso orale
Atorvastatin and atorvastatin-metabolites are substrates of P-glycoprotein.
Portogallo
Coadministration of atorvastatin 10 mg OD and erythromycin (500 mg QID), or atorvastatin 10 mg OD and clarithromycin (500 mg BID), known inhibitors of cytochrome P450 3A4, were associated with higher plasma concentrations of atorvastatin.
40mg
Itraconazole
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Concomitant administration of atorvastatin 40 mg and itraconazole 200 mg daily resulted in a 3-fold increase in atorvastatin AUC.
Uso orale
Protease inhibitors
Portogallo
Contains one or more components that inhibit CYP3A4 and can increase plasma concentrations of medicinal products metabolized by CYP3A4.
80mg
Inducers of cytochrome P450 3A4
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The effect of inducers of cytochrome P450 3A4 (e. g. rifampicin or phenytoin) on {PRODUCT NAME} is unknown.
Spagna
Other concomitant therapy
PARKE-DAVIS, S. L.
Gemfibrozil / fibric acid derivatives The risk of atorvastatin-induced myopathy may be increased with the concomitant use of fibric acid derivatives.
10mg
Patients taking digoxin should be monitored appropriately.
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Oral contraceptives Coadministration of {PRODUCT NAME} with an oral contraceptive produced increases in plasma concentrations of norethindrone and ethinyl oestradiol.
Uso orale
17 Colestipol Plasma concentrations of atorvastatin and its active metabolites were lower (by approx.
Spagna
35%; however, LDL-C reduction was not altered.
PARKE-DAVIS, S. L.
Phenazone Coadministration of multiple doses of {PRODUCT NAME} and phenazone showed little or no detectable effect in the clearance of phenazone.
20mg
Cimetidine An interaction study with cimetidine and {PRODUCT NAME} was conducted, and no interaction was seen.
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Amlodipine Atorvastatin pharmacokinetics were not altered by the coadministration of atorvastatin 80 mg and amlodipine 10 mg at steady state.
Uso orale
Other In clinical studies in which {PRODUCT NAME} was administered with antihypertensives or hypoglycaemic agents no clinically significant interactions were seen.
Spagna
There is evidence from animal studies that HMG-CoA reductase inhibitors may influence the development of embryos or foetuses.
40mg
It is not known whether this medicinal product or its metabolites are excreted in human milk.
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4.7 Effects on ability to drive and use machines
Uso orale
{PRODUCT NAME} has negligible influence on the ability to drive and use machines.
Spagna
Less than 2% of patients were discontinued from clinical trials due to side effects attributed to {PRODUCT NAME}.
80mg
Based on data from clinical studies and extensive post-marketing experience, the following table presents the adverse event profile for {PRODUCT NAME}.
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Estimated frequencies of events are ranked according to the following convention: common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000); very rare (≤ 1/ 10,000).
Uso orale
Gastrointestinal disorders
3 Stato Membro Svezia
Uncommon: anorexia, vomiting.
Titolare dell’ Autorizzazione all’ Immissione in Commercio Pfizer AB
Blood and lymphatic system disorders
Nome di Fantasia Lipitor
Uncommon: thrombocytopenia.
Dosaggio 10mg
Immune system disorders
Forma farmaceutica Compresse rivestite con film
Common: allergic reactions.
Via di somministrazione Uso orale
Endocrine disorders
Svezia
Common: insomnia.
20mg
Nervous system disorders
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Uncommon: peripheral neuropathy.
Uso orale
Hepato-biliary disorders
Svezia
Uncommon: urticaria.
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Ear and Labyrinth Disorders
Uso orale
Uncommon: tinnitus
Svezia
Reproductive system disorders
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Uncommon: impotence.
Uso orale
General disorders
4 ALLEGATO II
Uncommon: malaise, weight gain.
CONCLUSIONI SCIENTIFICHE E MOTIVI DELLA MODIFICA DEL RIASSUNTO DELLE CARATTERISTICHE DEL PRODOTTO PRESENTATI DALL’ EMEA
Investigations
5 CONCLUSIONI SCIENTIFICHE
As with other HMG-CoA reductase inhibitors elevated serum transaminases have been reported in patients receiving {PRODUCT NAME}.
SINTESI GENERALE DELLA VALUTAZIONE SCIENTIFICA DELL’ ATORVASTATINA (Sortis e denominazioni associate – cfr. allegato I)
These changes were usually mild, transient, and did not require interruption of treatment.
Sortis e denominazioni associate contengono atorvastatina, un noto inibitore dell’ HMG-CoA reduttasi (statina) registrato nell’ UE dal 1996 tramite la procedura di mutuo riconoscimento e le procedure a livello nazionale.
Clinically important (> 3 times upper normal limit) elevations in serum transaminases occurred in 0.8% patients on {PRODUCT NAME}.
Le indicazioni attualmente approvate per l’ atorvastatina sono:
These elevations were dose related and were reversible in all patients.
- in aggiunta alla dieta, per la riduzione di livelli elevati di colesterolo totale, colesterolo LDL,
Elevated serum creatine phosphokinase (CPK) levels greater than 3 times upper limit of normal occurred in 2.5% of patients on {PRODUCT NAME}, similar to other HMG-CoA reductase inhibitors in clinical trials.
apolipoproteina B e trigliceridi in pazienti con ipercolesterolemia primaria (inclusa l’ ipercolesterolemia familiare di tipo eterozigote) o iperlipidemia combinata (mista), corrispondenti rispettivamente ai tipi IIa e IIb della classificazione di Fredrickson, in caso di risposta inadeguata alla dieta e ad altri trattamenti non farmacologici;
Levels above 10 times the normal upper range occurred in 0.4% {PRODUCT NAME}-treated patients (see section 4.4).
familiare di tipo omozigote in aggiunta ad altri trattamenti ipolipemizzanti (ad esempio LDL aferesi) o quando tali trattamenti non siano disponibili.
4.9 Overdose
Informazioni generali sulla modifica di tipo II attraverso la procedura di mutuo riconoscimento Nel fascicolo originario sulla modifica di tipo II presentato con procedura di mutuo riconoscimento, il richiedente propone la seguente indicazione: “ Prevenzione di eventi cardiovascolari nei pazienti con fattori di rischio multipli (ad esempio pazienti diabetici di tipo 2 con un fattore di rischio e pazienti ipertesi con tre fattori di rischio) con colesterolemia normale o elevata ma senza una cardiopatia coronarica (CHD) clinicamente evidente”.
Specific treatment is not available for {PRODUCT NAME} overdosage.
Tale formulazione si basa sui risultati di due studi randomizzati controllati condotti sull’ atorvastatina 10 mg per la prevenzione primaria della malattia cardiovascolare (CVD).
Should an overdose occur, the patient should be treated symptomatically and supportive measures instituted, as required.
L’ atorvastatina ha prodotto una significativa diminuzione della frequenza di eventi coronarici e cardiovascolari, ictus e procedure di rivascolarizzazione sull’ intera coorte dello studio.
Liver function tests should be performed and serum CPK levels should be monitored.
Lo studio CARDS ha riguardato 2 838 pazienti di età compresa tra 40 e 75 anni con colesterolemia da normale a moderatamente elevata, diabete di tipo 2 e un altro fattore di rischio cardiovascolare, senza cardiopatia coronarica clinicamente evidente.
Due to extensive atorvastatin binding to plasma proteins, haemodialysis is not expected to significantly enhance atorvastatin clearance.
Lo studio ha evidenziato da parte dell’ atorvastatina una significativa riduzione della frequenza di eventi cardiovascolari importanti, di infarto miocardico acuto e infarto miocardico silente fatali e non fatali nonché della frequenza degli ictus.
PHARMACOLOGICAL PROPERTIES
in tal modo limitando l’ indicazione alla popolazione oggetto dello studio CARDS e relegando i risultati dello studio ASCOT-LLA in una descrizione contenuta nella sezione 5.1 del Riassunto delle caratteristiche del prodotto (RCP) in quanto non era stata dimostrata l’ efficacia sul sottogruppo femminile.
5.1 Pharmacodynamic properties
Al termine della procedura di mutuo riconoscimento è emersa una diversa valutazione tra gli Stati membri in merito alla dicitura dell’ indicazione proposta che dovrebbe rispecchiare in modo adeguato i
Pharmacotherapeutic group:
Il 1º dicembre 2005 la Spagna ha presentato al CHMP un deferimento per arbitrato.
C10AA05
Durante la seduta plenaria di dicembre, il CHMP ha adottato un elenco di domande incentrato sui seguenti punti:
Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme responsible for the conversion of 3-hydroxy-3-methyl-glutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol.
In quale modo l’ RCP possa rispecchiare in modo adeguato l’ assenza di effetti significativi a favore dell’ atorvastatina rispetto all’ endpoint primario composito e a vari endpoint secondari per il sottogruppo femminile.
Triglycerides and cholesterol in the liver are incorporated into very low-density lipoproteins (VLDL) and released into the plasma for delivery to peripheral tissues.
Se si debba escludere dall’ indicazione proposta la popolazione target dello studio ASCOT-LLA, precludendo in tal modo il trattamento ai pazienti non diabetici con alto rischio cardiovascolare.
Atorvastatin lowers plasma cholesterol and lipoprotein serum concentrations by inhibiting HMG-CoA reductase and subsequently cholesterol biosynthesis in the liver and increases the number of hepatic LDL receptors on the cell surface for enhanced uptake and catabolism of LDL.
Se l’ effetto cardioprotettivo dell’ atorvastatina sia maggiore quando viene usata in associazione a specifiche terapie antipertensive e se ciò vada indicato nell’ RCP.
Atorvastatin reduces LDL production and the number of LDL particles.
In quale misura l’ indicazione terapeutica richiesta sia applicabile a dosi di atorvastatina diverse da quella testata negli studi CARDS e ASCOT-LLA.
Atorvastatin produces a profound and sustained increase in LDL receptor activity coupled with a beneficial change in the quality of circulating LDL particles.
Una rassegna delle indicazioni approvate per l’ atorvastatina in base agli studi ASCOT-LLA e CARDS in tutta l’ UE.
Atorvastatin is effective in reducing LDL-C in patients with
Valutazione dell’ efficacia clinica
20 homozygous familial hypercholesterolaemia, a population that has not usually responded to lipid- lowering medication.
L’ aspetto principale affrontato dal CHMP è costituito dai risultati dello studio ASCOT-LLA, in primo luogo la mancanza di benefici certi e le tendenze negative in termini di mortalità riscontrate nel sottogruppo femminile e, in secondo luogo, l’ impatto dell’ interazione osservata tra amlodipina (antipertensivo) e atorvastatina sugli esiti principali dello studio per alcuni sottogruppi.
Atorvastatin has been shown to reduce concentrations of total-C (30% - 46%), LDL-C (41% - 61%), apolipoprotein B (34% - 50%), and triglycerides (14% - 33%) while producing variable increases in HDL-C and apolipoprotein A1 in a dose response study.
Il richiedente ha presentato argomenti sostenendo che i risultati dello studio ASCOT-LLA che si riferiscono alle donne e che si basano sulle analisi per sottogruppo sono con molta probabilità risultati casuali e quindi, dal punto di vista scientifico, non sufficientemente solidi da costituire la base per una misura di regolamentazione.
These results are consistent in patients with heterozygous familial hypercholesterolaemia, nonfamilial forms of hypercholesterolaemia, and mixed hyperlipidaemia, including patients with noninsulin-dependent diabetes mellitus.
Il richiedente ha inoltre fornito argomenti adeguati e oggettivi contro un’ eventuale limitazione che escluda le donne dall’ indicazione proposta stanti le conoscenze attuali sugli effetti benefici della terapia con statine in generale e anche nelle donne, presentando anche i risultati di studi di sperimentazione, linee guida e raccomandazioni valide a livello internazionale.