Product Information Guide For Older Adults with AML ... - Leukine.com

Product Information Guide
For Older Adults with
AML Following Induction
Chemotherapy
LEUKINE is indicated for use following induction chemotherapy in
older adults with AML to shorten time to neutrophil recovery and to
reduce the incidence of severe and life-threatening infections and
infections resulting in death.
Please see Important Safety Considerations on pages 10-11
and full Prescribing Information in back pocket.
®

Clinical Pharmacology
GM-CSF in Hematopoiesis
Supports survival, clonal expansion, and differentiation
of progenitor cells 1,2 *
GM-CSF = granulocyte-macrophage colony-stimulating factor
*Clinical significance of in-vitro and in-vivo data is unknown.
2
Please see full Prescribing Information in back pocket.

Indication
Leukine ® (sargramostim) is indicated following
induction chemotherapy in older adult patients
with AML to shorten time to neutrophil recovery and
to reduce the incidence of severe and life-threatening
infections and infections resulting in death.
Clinical Experience
• FDA approved and in clinical use for 15 years
• in a Phase iii study versus placebo
— 75% of patients receiving Leukine achieved
AnC >500/mm 3 by day 16, compared to day
25 for patients receiving placebo.
— The Leukine arm had significantly fewer deaths
from infection (3 vs. 11, p=0.02).
— The majority of deaths in the placebo group
were associated with fungal infections, with
pneumonia as the primary infection.
Safety Considerations
• L eu k i n e is contra-indicated in
— Patients with excessive leukemic myeloid blasts
in bone marrow or peripheral blood (>10%)
— Patients with known hypersensitivity to
GM-CSF, yeast-derived products, or any
component of Leukine
— Patients undergoing chemotherapy or radiotherary
• Serious allergic or anaphylactic reactions have been
reported with Leukine. if serious allergic or anaphylactic
reactions occur, Leukine should be immediately
stopped and appropriate
therapy initiated.
Please see additional Important
Safety Considerations on pages 10-11.
3
OVERVIEW

Liquid LEUKINE ®
• Supplied as a multiple-use vial
• Shipped via overnight direct delivery
Lyophilized LEUKINE ®
LEUKINE is also available
in a lyophilized formulation
• Lyophilized powder: 250 mcg in a single-use vial
ready for sterile reconstitution
Please see Important Safety Considerations on pages 10-11
and full Prescribing Information in back pocket.
4
— Cold packs maintain proper
refrigerated temperature
• Stored at 2-8°C (36-46°F)
— Once the vial has been entered, liquid
Leukine ® may be stored in the vial for
up to 20 days at 2-8°C
— Discard any remaining solution after 20 days

How Supplied
Storage
• Refrigerate Leukine at 2-8°C (36-46°F)
• Do not freeze or shake Leukine
• Do not use Leukine beyond expiration date printed
on the vial
5
HOW SUppLIEd

LEUKINE ®
Please see Important Safety Considerations on pages 10-11
and full Prescribing Information in back pocket.
6
Dosing
Recommended dosing for adults
55 years and older with AML following
induction chemotherapy
dose modifications recommended under
certain circumstances
• if a severe adverse reaction occurs, reduce
Leukine ® dose by 50% or temporarily withhold
until reaction abates
• Complete blood count (CBC) differential is
recommended twice weekly during Leukine therapy
— interrupt Leukine treatment or reduce dose
by half if AnC exceeds 20,000 cells/mm 3
• Discontinue Leukine immediately if leukemic
regrowth occurs

Recommended doses of LEUKINE ® based
on body surface area
7
DoSIng

LEUKINE ®
Please see Important Safety Considerations on pages 10-11
and full Prescribing Information in back pocket.
8
Tolerability
Adverse event profile similar to placebo
Adverse Events Reported in 10% of AML Patients
Who Received IV LEUKInE or Placebo*
* Results of the pivotal study of Leukine involving patients aged 55 to 70 years
with de novo AML.

Management of common LEUKINE ® adverse events 5
•
•
•
•
•
9
TOLERAbILITy

drug interactions
Drugs that can increase white blood cells (WBCs), such
as lithium and corticosteroids, should be used with
caution while receiving Leukine ® (sargramostim).
interactions between Leukine and other drugs have
not been fully evaluated.
Important Safety Considerations
Leukine ® (sargramostim) is indicated for the following
uses: (i) following induction chemotherapy in older adult
patients with acute myelogenous leukemia (AML) to shorten
time to neutrophil recovery; (ii) for mobilization and following
transplantation of autologous peripheral blood progenitor
cells; (iii) for myeloid reconstitution after autologous or
allogeneic bone marrow transplantation (BMT); (iv) for use
in bone marrow transplantation failure or engraftment delay.
Leukine is contraindicated in patients with excessive
leukemic myeloid blasts in bone marrow or peripheral blood
(≥10%); in patients with known hypersensitivity to GM-CSF,
yeast-derived products, or any component of Leukine; and
for concomitant use with chemotherapy and radiotherapy.
Serious allergic or anaphylactic reactions have been
reported with Leukine. if any serious allergic or
anaphylactic reactions occur, Leukine therapy
should be immediately discontinued and appropriate
therapy initiated.
Liquid solutions containing benzyl alcohol (including
liquid Leukine) or lyophilized Leukine reconstituted
with Bacteriostatic Water for injection, uSP (0.9% benzyl
alcohol) should not be administered to neonates.
Leukine should be used with caution and monitored
in patients with preexisting fluid retention, pulmonary
infiltrates, or CHF; respiratory symptoms or disease;
cardiac symptoms or disease; and renal or
hepatic dysfunction.
Please see full Prescribing Information in back pocket.
10

edema, capillary leak syndrome, pleural and/or
pericardial effusion, supraventricular tachycardia,
sequestration of granulocytes in the pulmonary
circulation, and dyspnea have been reported in patients
after Leukine administration. Leukine has induced
the elevation of serum creatinine or billirubin and
hepatic enzymes in some patients. Monitoring of renal
and hepatic function in patients with preexisting renal
or hepatic dysfunction is recommended at least every
other week during Leukine administration.
Adverse events occurring in >10% of patients receiving
Leukine in controlled clinical trials and reported in a
higher frequency than placebo were: in AML patients –
(fever, skin reactions, metabolic disturbances, nausea,
vomiting, weight-loss, edema, anorexia); in Autologous
BMT patients – (asthenia, malaise, diarrhea, rash,
peripheral edema, urinary tract disorder); and
in Allogeneic BMT patients – (abdominal pain, chills,
chest pain, diarrhea, nausea, vomiting, hematemesis,
dysphagia, Gi hemorrhage, pruritus, bone pain,
arthralgia, eye hemorrhage, hypertension, tachycardia,
bilirubinemia, hyperglycemia, increased creatinine,
hypomagnesemia, edema, pharyngitis, epistaxis,
dyspnea, insomnia, anxiety, high Bun, and
high cholesterol).
if AnC >20,000 cells/mm 3 or if platelet counts
>500,000/mm 3 , Leukine administration should be
interrupted or the dose reduced by half. Twice weekly
monitoring of CBC with differential should be performed.
Leukine therapy should be discontinued if disease
progression is detected during treatment.
To report suspected adverse events, contact
Genzyme Corporation at 1-888-4RX-Leukine
or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
11
IMpORTANT SAFETy
CONSIdERATIONS

LEUKINE ®
Please see Important Safety Considerations on pages 10-11
and full Prescribing Information in back pocket.
12
Preparation
Steps for the preparation of LEUKINE
1. Liquid Leukine ® is formulated as a sterile,
preserved (1.1% benzyl alcohol), injectable solution
(500 mcg/mL) in a vial. Lyophilized Leukine is a
sterile, white, preservative-free powder (250 mcg)
that requires reconstitution with 1 mL Sterile Water
for injection, uSP, or 1 mL Bacteriostatic Water for
injection, uSP.
2. Liquid Leukine may be stored for up to 20 days at
2-8°C once the vial has been entered. Discard any
remaining solution after 20 days.
3. Lyophilized Leukine (250 mcg) should be
reconstituted aseptically with 1.0 mL of diluent
(see below). The contents of vials reconstituted
with different diluents should not be mixed together.
Sterile Water for Injection, USP (without
preservative): Lyophilized Leukine vials contain
no antibacterial preservative, and therefore
solutions prepared with Sterile Water for injection,
uSP should be administered as soon as possible,
and within 6 hours following reconstitution and/
or dilution for iV infusion. The vial should not be
re-entered or reused. Do not save any unused
portion for administration more than 6 hours
following reconstitution.
Bacteriostatic Water for Injection, USP (0.9% benzyl
alcohol): Reconstituted solutions prepared with
Bacteriostatic Water for injection, uSP (0.9% benzyl
alcohol) may be stored for up to 20 days at 2-8°C
prior to use. Discard reconstituted solution after
20 days. Previously reconstituted solutions

mixed with freshly reconstituted solutions must
be administered within 6 hours following mixing.
Preparations containing benzyl alcohol
(including liquid LEUKINE and lyophilized
LEUKINE reconstituted with Bacteriostatic
Water for Injection) should not be used in
neonates (see WARNINGS in the enclosed full
Prescribing information).
4. During reconstitution of lyophilized Leukine the
diluent should be directed at the side of the vial and
the contents gently swirled to avoid foaming during
dissolution. Avoid excessive or vigorous agitation;
do not shake.
5. Leukine should be used for SC injection without
further dilution. Dilution for iV infusion should be
performed in 0.9% Sodium Chloride injection,
uSP. if the final concentration of Leukine is
below 10 mcg/mL, Albumin (Human) at a final
concentration of 0.1% should be added to the
saline prior to addition of Leukine to prevent
adsorption to the components of the drug delivery
system. To obtain a final concentration of 0.1%
Albumin (Human), add 1 mg Albumin (Human)
per 1 mL 0.9% Sodium Chloride injection, uSP
(eg, use 1 mL 5% Albumin [Human] in 50 mL 0.9%
Sodium Chloride injection, uSP).
6. An in-line membrane filter should nOT be used
for iV infusion of Leukine.
13
pREpARATION

7. Store liquid Leukine ® and reconstituted lyophilized
Leukine solutions under refrigeration at 2-8°C
(36-46°F); DO nOT FReeZe.
8. in the absence of compatibility and stability
information, no other medication should be added
to infusion solutions containing Leukine. use only
0.9% Sodium Chloride injection, uSP to prepare
iV infusion solutions.
9. Aseptic technique should be employed in the
preparation of all Leukine solutions. To assure
correct concentration following reconstitution, care
should be exercised to eliminate any air bubbles
from the needle hub of the syringe used to prepare
the diluent. Parenteral drug products should
be inspected visually for particulate matter and
discoloration prior to administration. if particulate
matter is present or the solution is discolored, the
vial should not be used.
Please see Important Safety Considerations on pages 10-11
and full Prescribing Information in back pocket.
14

Overview of LEUKINE ®
DIRECT
Reimbursement Services
LEUKINE dIRECT assists patients and providers
with assessing individual reimbursement
situations by providing the following services:
VERIFyING INSURANCE bENEFITS
NAVIGATING pRIOR AUTHORIZATION pROCESSES
IdENTIFyING SOURCES OF ALTERNATE COVERAGE
COdING ANd CLAIMS SUbMISSION SUppORT
STRATEGIES TO AppEAL CLAIMS
pATIENT ASSISTANCE pROGRAMS (pAp)
Leukine DiReCT reimbursement specialists are
available to assist you with questions related to
reimbursement support and services for therapy
with Leukine. To reach a reimbursement specialist,
please call the Leukine DiReCT Program at
888.4RX.Leukine (888.479.5385), option 3, between
Monday and Friday from 9 a.m. to 7 p.m. eT.
15
REIMbURSEMENT
SUppORT

For Clinical Support
Call LEUKLine—A toll-free line to answer
LEUKINE ® questions
• Healthcare Professionals available Monday
through Friday from 8:00 a.m. to 6:00 p.m. eT
1-877-3LEUKINE (1-877-353-8546)
Or visit us at www.leukine.com
Please see Important Safety Considerations on pages 10-11
and full Prescribing Information in back pocket.
16

To learn more about LEUKInE ® ,
please call LEUKLine,
our toll-free support line at
1-877-3LEUKInE
(1-877-353-8546)
or visit us at www.leukine.com.
17
LEUKLine

Notes:
Please see Important Safety Considerations on pages 10-11
and full Prescribing Information in back pocket.
18

References:
1. Nemunaitis J, Cox J, Meyer W, et al. Comparison of neutrophil and monocyte function by microbicidal
cell-kill assay in patients with cancer receiving granulocyte colony-stimulating factor, granulocyte-macrophage
colony-stimulating factor, or no cytokine after cytotoxic chemotherapy: a phase II trial. Am J Clin Oncol.
1998;21:308-312. 2. Holter JL, Ozer H. Hematopoietic growth factors. In: DeVita VT Jr, Hellman S, Rosenberg
SA, eds. Cancer: Principles & Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins;
2005:2442-2459. 3. Haynes BF, Soderberg KA, Fauci AS. Introduction to the Immune System. In: Fauci AS,
Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J, eds. Harrison’s Principles of Internal
Medicine, 17th Edition. 2008:2019:2044. 4. NEUPOGEN® (filgrastim) [package insert]. Thousand Oaks,
Calif: Amgen Inc; 2007. 5. Buchsel PC, Forgey A, Grape FB, Hamann SS. Granulocyte macrophage colonystimulating
factor: current practice and novel approaches. Clin J Oncol Nurs. 2002;6:198-205. 6. LEUKINE®
(sargramostim) [package insert]. Seattle, Wash: Bayer HealthCare Pharmaceuticals Inc.; 2008. 7. Rowe JM,
Rubin A, Mazza JJ, et al. Incidence of infections in adult patients (> 55 years) with acute myeloid leukemia
treated with yeast-derived GM-CSF (sargramostim): results of a double-blind prospective study by the Eastern
Cooperative Oncology Group. In: Hiddemann W, et al, eds. Acute Leukemias V: Experimental Approaches and
Management of Refractory Diseases. Berlin, Germany: Springer-Verlag; 1996:178-184.
19

Product Information Guide
For Older Adults with
AML Following Induction
Chemotherapy
Please see Important Safety Considerations on pages 10-11
and full Prescribing Information in back pocket.
Manufactured by Bayer HealthCare Pharmaceuticals, Seattle, WA 98101.
Distributed by Genzyme Corporation, Cambridge, MA 02142.
Leukine is a registered trademark licensed to Genzyme Corporation.
© 2010 Genzyme Corporation. All rights reserved LEU/US/P077/1010 Printed in USA October 2010
®