AUTOMATIC NEEDLE GUARD (ANG)User Training Guide

Aranesp® provides safe and convenient administration options

• The ANG prefilled syringe helps simplify administration and protects against unintentional needlesticks.

• No assembly required: – The ANG prefilled syringe comes ready to use.

• Prefilled syringes simplify dosing preparation.

• Removable flag label allows for easy administration tracking.

• Amgen is committed to making injections more secure for you and your patients.

Aranesp® Brief Prescribing InformationAranesp® (darbepoetin alfa) Prefilled Syringe (with Needle Guard) Brief Prescribing InformationPlease refer to the Summary of Product Characteristics before prescribing Aranesp®.Pharmaceutical Form: Solution for injection presented in prefilled pens containing 150, 300, and 500 micrograms of darbepoetin alfa, for single-dose use only.Indication: Treatment of symptomatic anaemia in adult cancer patients with non-myeloid malignancies receiving chemotherapy.Dosage and Administration: Cancer patients: Aranesp® should be administered by the subcutaneous route to patients with anaemia (e.g. haemoglobin concentration ≤10 g/dL (6.2 mmol/l)) in order to increase haemoglobin to not greater than 12 g/dL (7.5 mmol/l). Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary. Due to intra-patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/dL (6.2 mmol/l) to 12 g/dL (7.5 mmol/l). A sustained haemoglobin level of greater than 12 g/dL (7.5 mmol/l) should be avoided; guidance for appropriate dose adjustments for when haemoglobin values exceeding 12 g/dL (7.5 mmol/l) are observed are described below. The recommended initial dose is 500 µg (6.75 µg/kg) given once every three weeks, or once weekly dosing can be given at 2.25 µg/kg body weight. If the clinical response of the patient (fatigue, haemoglobin response) is inadequate after nine weeks, further therapy may not be effective. Aranesp® therapy should be discontinued approximately four weeks after the end of chemotherapy. Once the therapeutic objective for an individual patient has been achieved, the dose should be reduced by 25 to 50% in order to ensure that the lowest approved dose of Aranesp® is used to maintain haemoglobin at a level that controls the symptoms of anaemia. Appropriate dose titration between 500 µg, 300 µg, and 150 µg should be considered. Patients should be monitored closely, if the haemoglobin exceeds 12 g/dL (7.5 mmol/l), the dose should be reduced by approximately 25 to 50%. Treatment with Aranesp® should be temporarily discontinued if haemoglobin levels exceed 13 g/dL (8.1 mmol/l). Therapy should be reinitiated at approximately 25% lower than the previous dose after haemoglobin levels fall to 12 g/dL (7.5 mmol/l) or below. If the rise in haemoglobin is greater than 2 g/dL (1.25 mmol/l) in 4 weeks, the dose should be reduced by 25 to 50%.Contraindications: Hypersensitivity to darbepoetin alfa, r-HuEPO or any of the excipients. Poorly controlled hypertension.Special Warnings and Precautions: General blood pressure should be monitored in all patients, particularly during initiation of Aranesp® therapy. If blood pressure is difficult to control by initiation of appropriate measures, the haemoglobin may be reduced by decreasing or withholding the dose of Aranesp®. Iron status should be evaluated for all patients prior to and during treatment and supplementary iron therapy may be necessary. Non-response to therapy with Aranesp® should prompt a search for causative factors. Deficiencies of iron, folic acid or vitamin B12 reduce the effectiveness of erythropoiesis-stimulating agents and should therefore be corrected. Intercurrent infections, inflammatory or traumatic episodes, occult blood loss, haemolysis, severe aluminium toxicity, underlying diseases, or bone marrow fibrosis may also compromise the erythropoietic response. A reticulocyte count should be considered as part of the evaluation. If typical causes of non-response are excluded, and the patient has reticulocytopenia, an examination of the bone marrow should be considered. If the bone marrow is consistent with PRCA, testing for anti-erythropoietin antibodies should be performed. Pure red cell aplasia caused by neutralising anti-erythropoietin antibodies has been reported in association with recombinant erythropoietic proteins, including darbepoetin alfa. These antibodies have been shown to cross-react with all erythropoietic proteins, and patients suspected or confirmed to have neutralising antibodies to erythropoietin should not be switched to darbepoetin alfa. Active liver disease was an exclusion criteria in all studies of Aranesp®, therefore no data are available from patients with impaired liver function. Since the liver is thought to be the principal route of elimination of Aranesp® and r-HuEPO, Aranesp® should be used with caution in patients with liver disease. Aranesp® should also be used with caution in those patients with sickle cell anaemia or epilepsy. Convulsions have been reported in patients receiving Aranesp®. Misuse of Aranesp® by healthy persons may lead to an excessive increase in packed cell volume. This may be associated with life-threatening complications of the cardiovascular system. The needle cover of the prefilled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions. In patients with chronic renal failure, maintenance haemoglobin concentration should not exceed the upper limit of the target haemoglobin concentration. In clinical studies, an increased risk of death, serious cardiovascular events and vascular access thrombosis was observed when erythropoiesis-stimulating agents (ESAs) were administered to target a haemoglobin of greater than 12 g/dL (7.5 mmol/l). Controlled clinical trials have not shown significant benefits attributable to the administration of epoetins when haemoglobin concentration is increased beyond the level necessary to control symptoms of anaemia and to avoid blood transfusion. Cancer patients: Effect on tumour growth. Epoetins are growth factors that primarily stimulate red blood cell production. Erythropoietin receptors may be expressed on the surface of a variety of tumour cells. As with all growth factors, there is a concern that epoetins could stimulate the growth of tumours. In several controlled studies, epoetins have not been shown to improve overall survival or decrease the risk of tumour progression in patients with anaemia associated with cancer. In controlled clinical studies, use of Aranesp® and other erythropoiesis-stimulating agents (ESAs) have shown: shortened time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target a haemoglobin of greater than 14 g/dL (8.7 mmol/l) (ESAs are not indicated for use in this patient population); shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target a haemoglobin of 12-14 g/dL (7.5-8.7 mmol/l); increased risk of death when administered to target a haemoglobin of 12 g/dL (7.5 mmol/l) in patients with active malignant disease receiving neither chemotherapy nor radiation therapy (ESAs are not indicated for use in this patient population). In patients with solid tumours or lymphoproliferative malignancies, if the haemoglobin value exceeds 12 g/dL (7.5 mmol/l), the dosage adaptation described in the Posology and Method of Administration section should be closely respected, in order to minimise the potential risk of thromboembolic events. In view of the above, in some clinical situations blood transfusion should be the preferred treatment for the management of anaemia in patients with cancer. The decision to administer recombinant erythropoietins should be based on a benefit-risk assessment with the participation of the individual patient, which should take into account the specific clinical context. Factors that should be considered in this assessment should include the type of tumour and its stage; the degree of anaemia; life-expectancy; the environment in which the patient is being treated; and patient preference. Platelet counts and haemoglobin level should also be monitored at regular intervals.Pregnancy and Lactation: No adequate experience in human pregnancy and lactation. Exercise caution when prescribing Aranesp® to pregnant women. Do not administer to women who are breastfeeding. When Aranesp® therapy is absolutely indicated, breastfeeding must be discontinued.Undesirable Effects: General: There have been reports of serious allergic reactions including anaphylactic reaction, angioedema, dyspnoea, skin rash and urticaria associated with darbepoetin alfa. Clinical Trial Experience - Cancer patients: Adverse reactions were determined based on pooled data from seven randomised, double-blind, placebo-controlled studies of Aranesp® with a total of 2112 patients (Aranesp® 1200, placebo 912). Patients with solid tumours (e.g., lung, breast, colon, ovarian cancers) and lymphoid malignancies (e.g., lymphoma, multiple myeloma) were enrolled in the clinical studies. Incidence of undesirable effects considered related to treatment with Aranesp® from controlled clinical studies: Very common (≥1/10) Oedema; Common (≥1/100 to <1/10) Rash/Erythema, injection site pain, Thromboembolic events, including pulmonary embolism. Postmarketing Experience - Cancer patients: The following adverse reactions have been identified during postmarketing use of Aranesp®: (1) Pure Red Cell Aplasia - In isolated cases, neutralising anti-erythropoietin antibody mediated pure red cell aplasia (PRCA) associated with Aranesp® therapy have been reported predominantly in patients with CRF treated subcutaneously. In case PRCA is diagnosed, therapy with Aranesp® must be discontinued and patients should not be switched to another recombinant erythropoietic protein; (2) Allergic reactions, including anaphylactic reaction, angioedema, skin rash and urticaria; (3) Convulsions. Overdose: The therapeutic margin of Aranesp® is very wide. In the event of polycythaemia, Aranesp® should be temporarily withheld. If clinically indicated, phlebotomy may be performed.Pharmaceutical Precautions: Aranesp® should not be mixed or administered as an infusion with other medicinal products. Store at 2°C to 8°C (in a refrigerator). Do not freeze. Keep container in outer carton to protect from light. For ambulatory use, Aranesp® may be removed from storage once for a maximum single period of 7 days at room temperature (up to 25°C). The Aranesp® SureClick™ prefilled pen delivers the complete dose of each presentation.Legal Category: Medicinal product subject to restricted medical prescription.Presentation and Marketing Authorisation Numbers:Aranesp® 150 µg: 1 prefilled pen: EU/1/01/185/054;Aranesp® 300 µg: 1 prefilled pen: EU/1/01/185/055;Aranesp® 500 µg: 1 prefilled pen: EU/1/01/185/056;Aranesp® 150 µg: 1 prefilled syringe with needle guard: EU/1/01/185/094;Aranesp® 150 µg: 4 prefilled syringes with needle guard: EU/1/01/185/095;Aranesp® 300 µg: 1 prefilled syringe with needle guard: EU/1/01/185/096; Aranesp® 300 µg: 4 prefilled syringes with needle guard: EU/1/01/185/097;Aranesp® 500 µg: 1 prefilled syringe with needle guard: EU/1/01/185/098;Aranesp® 500 µg: 4 prefilled syringes with needle guard: EU/1/01/185/099;Availability of presentations may vary in national regions.Marketing Authorisation Holder: Amgen Europe B.V., Minervum 7061, NL-4817 ZK Breda, The Netherlands. Further information is available from Amgen (Europe) GmbH, Dammstrasse 23, P.O. Box 1557, CH-6314 Zug, Switzerland. Additional information may be obtained from your local Amgen office.Date of Preparation: June 2009. Amgen (Europe) GmbH Zug, Switzerland

ARANESP® VOORGEVULDE SPUIT MET AUTOMATISCHE NAALDBESCHERMER

Handleiding voor gebruikers

Aranesp® biedt veilige en gemakkelijke toedieningsmogelijkheden

• De voorgevulde spuit met Automatische Naaldbeschermer vereenvoudigt toediening en beschermt tegen prikincidenten2

• Klaar voor gebruik: de voorgevulde spuit met Automatische Naaldbeschermer is kant en klaar voor gebruik2

• Voorgevulde spuiten vereenvoudigen doseren2

• Verwijderbare fl ag-label maken administratie makkelijker

• Amgen heeft zich gecommiteerd aan het veiliger maken van injecties voor u en uw patient

Aranesp® Samenstelling: oplossing voor injectievloeistof met darbepoetin alfa. Aranesp SureClick uitsluitend voor s.c. gebruik. Afl everingsvorm: Aranesp SureClick: verpakking met één voorgevulde pen met 20, 40, 60, 80, 100, 150, 300 of 500 microgram. Aranesp voorgevulde spuiten met automatische naaldbeschermer: verpakking met vier voorgevulde spuiten met 20, 30, 40, 50, 60, 80, 100, 130 of 150 microgram of verpakking met één voorgevulde spuit met 300 of 500 microgram. Aranesp voorgevulde spuiten: verpakking met vier voorgevulde spuiten met10 microgram. Farmacotherapeutische categorie: Geneesmiddel tegen anemie, ATC-code: B03XA02. Indicaties en dosering: Behandeling van symptomatische anemie t.g.v. chronische nierinsuffi ciëntie bij volwassenen en kinderen. Behandeling van symptomatische anemie bij volwassen kankerpatiënten met non-myeloïde maligniteiten die chemotherapie toegediend krijgen. Dosering is afhankelijk van de indicatie (zie geregistreerde productinformatie). Contra-indicaties: Overgevoeligheid voor darbepoetin alfa, r-HuEPO of één van de hulpstoffen. Slecht gecontroleerde hypertensie. Bijzondere waarschuwingen en voorzorgen bij gebruik: Algemeen: De bloeddruk dient te worden gecontroleerd bij alle patiënten, vooral bij aanvang van de behandeling met Aranesp. Aanbevolen wordt om de Hb streefwaarden niet te overschrijden. Voor een effectieve erythropoëse, de ijzerstatus evalueren bij alle patiënten voor en tijdens de behandeling, een supplementaire ijzertherapie kan noodzakelijk zijn. Erytrocytaire aplasie (PRCA) veroorzaakt door neutraliserende anti-erytropoëtine antilichamen is gerapporteerd in samenhang met recombinante erytropoëtische eiwitten, inclusief darbepoetin alfa. Patiënten met vermoede of bevestigde neutraliserende antilichamen t.g.v. erytropoëtine niet overzetten op Aranesp. Aranesp met voorzichtigheid gebruiken bij patiënten met een leveraandoening. Voorzichtigheid betrachten bij sikkelcelanemie of epilepsie. Patiënten met chronische nierinsuffi ciëntie: In de onderhoudsfase de bovenste limiet van de Hb streefwaarde niet overschrijden. Tijdens klinische onderzoeken werd een verhoogd risico op overlijden en ernstige cardiovasculaire gebeurtenissen waargenomen wanneer ESA’s werden toegediend met streefwaarden van de Hb concentratie hoger dan 7,5 mmol/l. IJzersuppletie is aanbevolen bij alle patiënten met een serumferritinespiegel < 100 µg/l of een transferrinesaturatie < 20%. Bij patiënten met chronische nierinsuffi ciëntie en klinische aanwijzingen van ischemische hartziekten of congestief hartfalen, streefwaarde van Hb individueel bepalen. Bij deze patiënten een bovengrens van 7,5 mmol/l nastreven, tenzij ernstige symptomen (bv. angina pectoris) anders bepalen. De kaliumspiegels regelmatig controleren tijdens de behandeling. Indien een gestegen of stijgende kaliumspiegel wordt waargenomen, overwegen om de toediening van Aranesp stop te zetten tot normale spiegels. Patiënten met kanker: Een verhoogd risico op overlijden wanneer toegediend om een Hb concentratie van 7,5 mmol/l te bereiken bij patiënten met actieve maligniteiten die noch chemotherapie noch radiotherapie ontvangen. ESA’s zijn niet geïndiceerd voor gebruik in deze patiëntengroep. Zoals bij alle groeifactoren is er bezorgdheid dat epoëtines de groei van tumoren zou kunnen stimuleren. In sommige klinische situaties heeft een bloedtransfusie de voorkeur. Bij solide tumoren of lymphoproliferatieve maligniteiten Hb > 7,5 mmol/l dosisaanpassing volgen om potentieel risico op thrombo-embolische gebeurtenissen te minimaliseren. Aantal bloedplaatjes en Hb dienen regelmatig te worden gecontroleerd. Interacties: De tot op heden verkregen klinische resultaten wijzen niet op enige interactie van Aranesp met andere stoffen. Er is een mogelijkheid op interactie met geneesmiddelen die in hoge mate worden gebonden aan rode bloedcellen bijvoorbeeld cyclosporine en tacrolimus. Indien darbepoetin alfa samen gegeven wordt met een van deze geneesmiddelen, bloedspiegels van deze geneesmiddelen controleren en de dosering aanpassen als het Hb stijgt. Zwangerschap en borstvoeding: Voorzichtigheid is geboden bij het voorschrijven aan zwangere vrouwen. Aranesp niet toedienen aan vrouwen die borstvoeding geven. Wanneer behandeling met Aranesp absoluut is aangewezen, dienen vrouwen te stoppen met het geven van borstvoeding. Bijwerkingen: Algemeen: ernstige allergische reacties waaronder anafylactische reactie, angioedeem, kortademigheid, huiduitslag en urticaria. In klinisch onderzoek: Patiënten met chronische nierinsuffi ciëntie: zeer vaak: hypertensie. Vaak: huiduitslag, erytheem en pijn op de injectieplaats. Patiënten met kanker: zeer vaak: oedeem. Vaak: huiduitslag, erytheem, trombo-embolische voorvallen waaronder pulmonair embolisme en pijn op de injectieplaats. Postmarketing ervaring: In geïsoleerde gevallen: erytrocytaire aplasie (PRCA) veroorzaakt door neutraliserende anti-erytropoëtine antilichamen. Allergische reacties, waaronder anafylactische reactie, angioedeem, huiduitslag en urticaria. Convulsies. Vergoeding: U.R. Aranesp wordt volledig vergoed. Voor prijzen zie Z-index. Voor meer informatie zie de geregistreerde productinformatie.Amgen BV te Breda, tel. 076-5732500.Versie 2009295 / april 2009

Referenties 1. Samenvatting van de productkenmerken Aranesp®(SureClick™), april 2009,

Amgen B.V.2. NIOSH Alert 1999, Preventing Needle stick injuries in health care settings, publ. No.

2000-108 (www.cdc.gov/niosh).

AMG-2009376

312116_AMG_folderAranesp.indd 1 2-9-09 11:30

INJECTIE INSTRUCTIES VOOR DE ARANESP® VOORGEVULDE SPUIT MET

AUTOMATISCHE NAALDBESCHERMER.

STAP 2: Activeren van de automatische naaldbeschermer

• Nadat de vloeistof is ingespoten, trekt u de spuit terug en laat u de huid los. Let hierbij op het volgende:

• Houd druk op de zuiger terwijl u de naald uit de huid verwijdert• Laat langzaam de druk op de zuiger afnemen, zodat de spuit auto-

matisch omhoog kan bewegen totdat de volledige naald bedekt is door de naaldbeschermer en

STAP 3: Verwijderen van het fl ag-label (optioneel)

• Houd de spuit zoals getoond in de afbeelding, draai de zuiger naar u toe totdat u in de opening van het venster de fl ap van het labelkunt zien

• Draai de zuiger van u af totdat de fl ap tegen de plastic random hoog steekt

• Grijp de fl ap stevig vast, trek hem omhoog door het venster en scheur af langs de perforaties aan de onderkant.

IntroductieDe Aranesp® voorgevulde spuit met Automatische Naaldbeschermer wordt gebruikt zoals een conventionele spuit. De medicatie wordt toegediend door de zuiger helemaal naar beneden te duwen. Na het volledig toedienen van de injectie èn zodra de druk van de zuiger wordt gehaald, wordt automatisch een naaldbeschermer geactiveerd. Indien gewenst kan daarna het “fl ag-label” van de spuit verwijderd worden, waarna de voorgevulde spuit met Automatische Naaldbeschermer op dezelfde manier in een speciale naaldencontainer weg-gegooid kan worden als een conventionele spuit.

Voor de start• Neem de spuit met Aranesp uit de koelkast, en laat op kamertemperatuur

komen. Voor prettiger injecteren kunt u de voorgevulde spuit 30 minuten op kamertemperatuur laten komen alvorens te injecteren. De voorgevulde spuit be-slist niet opwarmen (bijvoorbeeld niet verwarmen in magnetron of warm water).

• De voorgevulde spuit niet schudden.• Controleer of het de dosis is die de arts u heeft voorgeschreven.• Neem de voorgevulde spuit uit de verpakking.• Controleer de uiterste gebruikdatum op het etiket van de voorgevulde spuit

(EXP:). Niet gebruiken na de laatste dag van de vermelde maand.• Controleer hoe Aranesp eruit ziet. Het moet een heldere of enigzins parelach-

tige vloeistof zijn. Als de vloeistof troebel is of deeltjes bevat, mag u deze niet gebruiken.

• Was uw handen grondig.• Kies een prettige, goed verlichte plaats en zet alles wat u nodig heeft binnen

handbereik (de Aranesp voorgevulde spuit, alcoholdoekjes en een naalden-container voor de gebruikte spuiten).

• Desinfecteer de huid, bijvoorbeeld met een alcoholdoekje.

De beste plaatsen om uzelf te injecteren zijn:• De buik, behalve het gebied rond de navel,• De bovenkant van uw dijbenen.• Als u door iemand anders wordt geïnjecteerd, kan ook

de achterzijde van uw bovenarm worden gebruikt.• Verander van injectieplaats indien u merkt dat de

injectieplaats rood of gezwollen is.

STAP 1: Toedienen van de injectie

• Verwijder de grijze beschermdop, zorg ervoor dat u de zuiger en de naald niet aanraakt.

• Het is NIET NODIG om luchtbellen te verwijderen voordat u gaat injecteren.• Verwijder het “fl ag-label” NIET voordat u de injectie heeft toegediend (stap 1 & 2).• Desinfecteer uw huid met een alcoholdoekje en pak de huid tussen duim en

wijsvinger beet, zonder te knijpen.• Breng de naald volledig in de huid zoals gedemonstreerd door de verpleeg-

kundige of arts.• Trek de zuiger voorzichtig wat omhoog om te controleren of er geen bloedvat

is aangeprikt. Als u bloed in de spuit ziet, verwijder dan de naald en steek (na desinfecteren) op een andere plaats in de huid.

• Injecteer de vloeistof langzaam en gelijkmatig, waarbij u nog steeds de huid vasthoudt.

• Duw de zuiger langzaam zo ver mogelijk naar beneden, totdat alle vloeistof geïnjecteerd is.

LET OP: de Automatische Naaldbeschermer wordt alleen geactiveerd als de voorgevulde spuit volledig geleegd is.

Automatic Needle Guard (ANG) Prefilled Syringe

Administration Instructions

Introduction

This ANG prefilled syringe is used like a conventional syringe. Administer the medication by pushing the plunger all the way down. After delivering the full injection, a needle guard is automatically activated as you release pressure from the plunger. You can then remove the flag label tab if desired, and dispose of the ANG prefilled syringe as you would a conventional syringe.

Before You Start:

• Ensure that you have read the patient information leaflet instructions provided with this product.

• Make sure prefilled syringe is at room temperature before starting Step 1.

• Based upon the patient instructions, select and prepare an appropriate injection site.

• You DO NOT have to remove air bubbles before injecting.

• DO NOT remove flag label (Step 3) before administering injection (Steps 1 & 2).

1. Administer Injection

• Remove grey needle cap.

• To inject, slowly push the plunger down as far as it will go until all liquid is injected. A

Note: The ANG will not activate unless you completely empty the prefilled syringe. B

A B

2. Deploy Needle Guard

• Keeping pressure on the plunger, remove the needle from the skin. C

• Slowly release pressure from the plunger, allowing the syringe to automatically move up until the entire needle is covered by the needle guard. D E

3. Remove Flag Label (optional)

• Hold the syringe as shown and rotate the plunger toward you until you can see the tab of the label within the opening of the window. F

• Rotate the plunger away from you until the tab sticks up against the plastic edge. G ]

• Grasp tab firmly, pull up through the window, and tear across bottom perforation. H

C D

E

GF

H

Properly Dispose of Syringe After Use

Automatic Needle Guard (ANG) Prefilled Syringe

Administration Instructions

Introduction

This ANG prefilled syringe is used like a conventional syringe. Administer the medication by pushing the plunger all the way down. After delivering the full injection, a needle guard is automatically activated as you release pressure from the plunger. You can then remove the flag label tab if desired, and dispose of the ANG prefilled syringe as you would a conventional syringe.

Before You Start:

• Ensure that you have read the patient information leaflet instructions provided with this product.

• Make sure prefilled syringe is at room temperature before starting Step 1.

• Based upon the patient instructions, select and prepare an appropriate injection site.

• You DO NOT have to remove air bubbles before injecting.

• DO NOT remove flag label (Step 3) before administering injection (Steps 1 & 2).

1. Administer Injection

• Remove grey needle cap.

• To inject, slowly push the plunger down as far as it will go until all liquid is injected. A

Note: The ANG will not activate unless you completely empty the prefilled syringe. B

A B

2. Deploy Needle Guard

• Keeping pressure on the plunger, remove the needle from the skin. C

• Slowly release pressure from the plunger, allowing the syringe to automatically move up until the entire needle is covered by the needle guard. D E

3. Remove Flag Label (optional)

• Hold the syringe as shown and rotate the plunger toward you until you can see the tab of the label within the opening of the window. F

• Rotate the plunger away from you until the tab sticks up against the plastic edge. G ]

• Grasp tab firmly, pull up through the window, and tear across bottom perforation. H

C D

E

GF

H

Properly Dispose of Syringe After Use

Automatic Needle Guard (ANG) Prefilled Syringe

Administration Instructions

Introduction

This ANG prefilled syringe is used like a conventional syringe. Administer the medication by pushing the plunger all the way down. After delivering the full injection, a needle guard is automatically activated as you release pressure from the plunger. You can then remove the flag label tab if desired, and dispose of the ANG prefilled syringe as you would a conventional syringe.

Before You Start:

• Ensure that you have read the patient information leaflet instructions provided with this product.

• Make sure prefilled syringe is at room temperature before starting Step 1.

• Based upon the patient instructions, select and prepare an appropriate injection site.

• You DO NOT have to remove air bubbles before injecting.

• DO NOT remove flag label (Step 3) before administering injection (Steps 1 & 2).

1. Administer Injection

• Remove grey needle cap.

• To inject, slowly push the plunger down as far as it will go until all liquid is injected. A

Note: The ANG will not activate unless you completely empty the prefilled syringe. B

A B

2. Deploy Needle Guard

• Keeping pressure on the plunger, remove the needle from the skin. C

• Slowly release pressure from the plunger, allowing the syringe to automatically move up until the entire needle is covered by the needle guard. D E

3. Remove Flag Label (optional)

• Hold the syringe as shown and rotate the plunger toward you until you can see the tab of the label within the opening of the window. F

• Rotate the plunger away from you until the tab sticks up against the plastic edge. G ]

• Grasp tab firmly, pull up through the window, and tear across bottom perforation. H

C D

E

GF

H

Properly Dispose of Syringe After Use

AUTOMATIC NEEDLE GUARD (ANG)User Training Guide

Aranesp® provides safe and convenient administration options

• The ANG prefilled syringe helps simplify administration and protects against unintentional needlesticks.

• No assembly required: – The ANG prefilled syringe comes ready to use.

• Prefilled syringes simplify dosing preparation.

• Removable flag label allows for easy administration tracking.

• Amgen is committed to making injections more secure for you and your patients.

Aranesp® Brief Prescribing InformationAranesp® (darbepoetin alfa) Prefilled Syringe (with Needle Guard) Brief Prescribing InformationPlease refer to the Summary of Product Characteristics before prescribing Aranesp®.Pharmaceutical Form: Solution for injection presented in prefilled pens containing 150, 300, and 500 micrograms of darbepoetin alfa, for single-dose use only.Indication: Treatment of symptomatic anaemia in adult cancer patients with non-myeloid malignancies receiving chemotherapy.Dosage and Administration: Cancer patients: Aranesp® should be administered by the subcutaneous route to patients with anaemia (e.g. haemoglobin concentration ≤10 g/dL (6.2 mmol/l)) in order to increase haemoglobin to not greater than 12 g/dL (7.5 mmol/l). Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary. Due to intra-patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/dL (6.2 mmol/l) to 12 g/dL (7.5 mmol/l). A sustained haemoglobin level of greater than 12 g/dL (7.5 mmol/l) should be avoided; guidance for appropriate dose adjustments for when haemoglobin values exceeding 12 g/dL (7.5 mmol/l) are observed are described below. The recommended initial dose is 500 µg (6.75 µg/kg) given once every three weeks, or once weekly dosing can be given at 2.25 µg/kg body weight. If the clinical response of the patient (fatigue, haemoglobin response) is inadequate after nine weeks, further therapy may not be effective. Aranesp® therapy should be discontinued approximately four weeks after the end of chemotherapy. Once the therapeutic objective for an individual patient has been achieved, the dose should be reduced by 25 to 50% in order to ensure that the lowest approved dose of Aranesp® is used to maintain haemoglobin at a level that controls the symptoms of anaemia. Appropriate dose titration between 500 µg, 300 µg, and 150 µg should be considered. Patients should be monitored closely, if the haemoglobin exceeds 12 g/dL (7.5 mmol/l), the dose should be reduced by approximately 25 to 50%. Treatment with Aranesp® should be temporarily discontinued if haemoglobin levels exceed 13 g/dL (8.1 mmol/l). Therapy should be reinitiated at approximately 25% lower than the previous dose after haemoglobin levels fall to 12 g/dL (7.5 mmol/l) or below. If the rise in haemoglobin is greater than 2 g/dL (1.25 mmol/l) in 4 weeks, the dose should be reduced by 25 to 50%.Contraindications: Hypersensitivity to darbepoetin alfa, r-HuEPO or any of the excipients. Poorly controlled hypertension.Special Warnings and Precautions: General blood pressure should be monitored in all patients, particularly during initiation of Aranesp® therapy. If blood pressure is difficult to control by initiation of appropriate measures, the haemoglobin may be reduced by decreasing or withholding the dose of Aranesp®. Iron status should be evaluated for all patients prior to and during treatment and supplementary iron therapy may be necessary. Non-response to therapy with Aranesp® should prompt a search for causative factors. Deficiencies of iron, folic acid or vitamin B12 reduce the effectiveness of erythropoiesis-stimulating agents and should therefore be corrected. Intercurrent infections, inflammatory or traumatic episodes, occult blood loss, haemolysis, severe aluminium toxicity, underlying diseases, or bone marrow fibrosis may also compromise the erythropoietic response. A reticulocyte count should be considered as part of the evaluation. If typical causes of non-response are excluded, and the patient has reticulocytopenia, an examination of the bone marrow should be considered. If the bone marrow is consistent with PRCA, testing for anti-erythropoietin antibodies should be performed. Pure red cell aplasia caused by neutralising anti-erythropoietin antibodies has been reported in association with recombinant erythropoietic proteins, including darbepoetin alfa. These antibodies have been shown to cross-react with all erythropoietic proteins, and patients suspected or confirmed to have neutralising antibodies to erythropoietin should not be switched to darbepoetin alfa. Active liver disease was an exclusion criteria in all studies of Aranesp®, therefore no data are available from patients with impaired liver function. Since the liver is thought to be the principal route of elimination of Aranesp® and r-HuEPO, Aranesp® should be used with caution in patients with liver disease. Aranesp® should also be used with caution in those patients with sickle cell anaemia or epilepsy. Convulsions have been reported in patients receiving Aranesp®. Misuse of Aranesp® by healthy persons may lead to an excessive increase in packed cell volume. This may be associated with life-threatening complications of the cardiovascular system. The needle cover of the prefilled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions. In patients with chronic renal failure, maintenance haemoglobin concentration should not exceed the upper limit of the target haemoglobin concentration. In clinical studies, an increased risk of death, serious cardiovascular events and vascular access thrombosis was observed when erythropoiesis-stimulating agents (ESAs) were administered to target a haemoglobin of greater than 12 g/dL (7.5 mmol/l). Controlled clinical trials have not shown significant benefits attributable to the administration of epoetins when haemoglobin concentration is increased beyond the level necessary to control symptoms of anaemia and to avoid blood transfusion. Cancer patients: Effect on tumour growth. Epoetins are growth factors that primarily stimulate red blood cell production. Erythropoietin receptors may be expressed on the surface of a variety of tumour cells. As with all growth factors, there is a concern that epoetins could stimulate the growth of tumours. In several controlled studies, epoetins have not been shown to improve overall survival or decrease the risk of tumour progression in patients with anaemia associated with cancer. In controlled clinical studies, use of Aranesp® and other erythropoiesis-stimulating agents (ESAs) have shown: shortened time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target a haemoglobin of greater than 14 g/dL (8.7 mmol/l) (ESAs are not indicated for use in this patient population); shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target a haemoglobin of 12-14 g/dL (7.5-8.7 mmol/l); increased risk of death when administered to target a haemoglobin of 12 g/dL (7.5 mmol/l) in patients with active malignant disease receiving neither chemotherapy nor radiation therapy (ESAs are not indicated for use in this patient population). In patients with solid tumours or lymphoproliferative malignancies, if the haemoglobin value exceeds 12 g/dL (7.5 mmol/l), the dosage adaptation described in the Posology and Method of Administration section should be closely respected, in order to minimise the potential risk of thromboembolic events. In view of the above, in some clinical situations blood transfusion should be the preferred treatment for the management of anaemia in patients with cancer. The decision to administer recombinant erythropoietins should be based on a benefit-risk assessment with the participation of the individual patient, which should take into account the specific clinical context. Factors that should be considered in this assessment should include the type of tumour and its stage; the degree of anaemia; life-expectancy; the environment in which the patient is being treated; and patient preference. Platelet counts and haemoglobin level should also be monitored at regular intervals.Pregnancy and Lactation: No adequate experience in human pregnancy and lactation. Exercise caution when prescribing Aranesp® to pregnant women. Do not administer to women who are breastfeeding. When Aranesp® therapy is absolutely indicated, breastfeeding must be discontinued.Undesirable Effects: General: There have been reports of serious allergic reactions including anaphylactic reaction, angioedema, dyspnoea, skin rash and urticaria associated with darbepoetin alfa. Clinical Trial Experience - Cancer patients: Adverse reactions were determined based on pooled data from seven randomised, double-blind, placebo-controlled studies of Aranesp® with a total of 2112 patients (Aranesp® 1200, placebo 912). Patients with solid tumours (e.g., lung, breast, colon, ovarian cancers) and lymphoid malignancies (e.g., lymphoma, multiple myeloma) were enrolled in the clinical studies. Incidence of undesirable effects considered related to treatment with Aranesp® from controlled clinical studies: Very common (≥1/10) Oedema; Common (≥1/100 to <1/10) Rash/Erythema, injection site pain, Thromboembolic events, including pulmonary embolism. Postmarketing Experience - Cancer patients: The following adverse reactions have been identified during postmarketing use of Aranesp®: (1) Pure Red Cell Aplasia - In isolated cases, neutralising anti-erythropoietin antibody mediated pure red cell aplasia (PRCA) associated with Aranesp® therapy have been reported predominantly in patients with CRF treated subcutaneously. In case PRCA is diagnosed, therapy with Aranesp® must be discontinued and patients should not be switched to another recombinant erythropoietic protein; (2) Allergic reactions, including anaphylactic reaction, angioedema, skin rash and urticaria; (3) Convulsions. Overdose: The therapeutic margin of Aranesp® is very wide. In the event of polycythaemia, Aranesp® should be temporarily withheld. If clinically indicated, phlebotomy may be performed.Pharmaceutical Precautions: Aranesp® should not be mixed or administered as an infusion with other medicinal products. Store at 2°C to 8°C (in a refrigerator). Do not freeze. Keep container in outer carton to protect from light. For ambulatory use, Aranesp® may be removed from storage once for a maximum single period of 7 days at room temperature (up to 25°C). The Aranesp® SureClick™ prefilled pen delivers the complete dose of each presentation.Legal Category: Medicinal product subject to restricted medical prescription.Presentation and Marketing Authorisation Numbers:Aranesp® 150 µg: 1 prefilled pen: EU/1/01/185/054;Aranesp® 300 µg: 1 prefilled pen: EU/1/01/185/055;Aranesp® 500 µg: 1 prefilled pen: EU/1/01/185/056;Aranesp® 150 µg: 1 prefilled syringe with needle guard: EU/1/01/185/094;Aranesp® 150 µg: 4 prefilled syringes with needle guard: EU/1/01/185/095;Aranesp® 300 µg: 1 prefilled syringe with needle guard: EU/1/01/185/096; Aranesp® 300 µg: 4 prefilled syringes with needle guard: EU/1/01/185/097;Aranesp® 500 µg: 1 prefilled syringe with needle guard: EU/1/01/185/098;Aranesp® 500 µg: 4 prefilled syringes with needle guard: EU/1/01/185/099;Availability of presentations may vary in national regions.Marketing Authorisation Holder: Amgen Europe B.V., Minervum 7061, NL-4817 ZK Breda, The Netherlands. Further information is available from Amgen (Europe) GmbH, Dammstrasse 23, P.O. Box 1557, CH-6314 Zug, Switzerland. Additional information may be obtained from your local Amgen office.Date of Preparation: June 2009. Amgen (Europe) GmbH Zug, Switzerland

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