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1. .,-:'
Date:
To:
Thru:
From:
Subject:
Drug Name(s):
Pediatric Exclusivity
Approval Date:
Application Type/Number:
Applicant/sponsor:
OSE RCM #:
Department of Health and Human Services
Public Health Service
Food and Drug Administration
Center for Drug Evaluation and Research
Offce of Surveilance and Epidemiology
October 22, 2010
Lisa L. Mathis MD, Associate Director
Pediatric and Maternal Health Staff (PMHS)
Office of New Drugs (ON D), CDER
and
M, Dianne Murphy, MD, Director
Office of Pediatric Therapeutics (OPT), OC
~. 1?-:i-l2-D l 0Bindi Nikhar, MD, Deputy Director.. ~ -' C 0
Division of Pharmacovigilance II (DPV II) ~
Office of Surveillance and Epidemiology (OSE),CDER
Robert Pratt, PharmD, Team Leader
Division of Pharmacovigilance II (DPV II) Offce of Surveillance and
Epidemiology (OSE), CDER
Corrinne Kulick, PharmD, Safety Evaluator
Division of Pharmacovigilance II (DPV II)
Office of Surveillance and Epidemiology (OS E), CDER
PREA: Pediatric Postmarketing Adverse Event Review
Neulasta (pegfilgrastim) injection
BLA 125031
Amgen Inc.
2010-1804

2. CONTENTS
EXECUTIVE SUMMARY ......................................... ........................... ........................... ..... ......... .... 1
1 BACKGROUND.......... ....................................... .............. ....... ................................. ................ 1
1.1 Product Formulations and Indications .............................. .............................................. 1
1.2 Pediatric Filing history............................ ...................................................... ..................2
1.3 Pediatric labeling ...................................... ............................................... .......................2
2 METHODS AND MATERIALS ................................................................................................2
2.1 AERS Search Criteria..................................................................................................... 2
3 AERS RESULTS FOR PEGFILGRASTIM ...... ........................................................................3
3.1 Crude Counts of All AERS Reports........................................................... .....................3
3.2 Characteristics From Pediatric Safety Review.... ........................................................... 4
4 DISCUSSION/SUMMARY OF PEDIATRIC CASES............................................................... 4
4.1 Deaths (n= 2) ........................ .................. ................................................... .....................4
4.2 Allergic-type events (n=4)............................. ..................................................................5
4.3 Miscellaneous events in the Unlabeled Indication Severe Chronic Neutropenia (n=5) .5
5 CONCLUSiONS...................................................................................................................... 6
6 RECOMMENDATIONS...........................................................................................................7
7 APPENDICES .........................................................................................................................7
7.1 Appendix A: Line listing of AERS cases associated with the use of pegfilgrastim in
children 0-16 years old, received by the FDA from U.S. approval (31 January 2002) to 31
August 2010 (n=24) ..................................................................................................................... 1

3. EXECUTIVE SUMMARY
In accordance with Pediatric Research Equity Act (PREA), the Division of Pharmacovigilance
(DPV) was asked to summarize post-marketing reports of adverse events associated with the use
of Neulasta (pegfilgrastim) in pediatric patients (0-16 years of age). The focus of this review is
pediatric deaths and pediatric reports of serious unlabeled adverse events with pegfilgrastim.
Pegfilgrastim is a chemically modified human granulocyte colony-stimulating factor (G-CSF)
indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients
with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a
clinically significant incidence of febrile neutropenia. The safety and effectiveness of pegfilgrastim
in pediatric patients has not been established.
We searched the Adverse Event Reporting System (AERS) database for all reports of adverse
events (serious and non-serious) up to the data lock date of 31 August 2010. AERS contained
3641 reports for pegfilgrastim; pediatric reports represented approximately 0.74 % of the total
(27/3641). Among 24 unique pediatric cases, we
observed the following:
. All but one of the pediatric cases reported adverse events that are qualitatively similar to those
currently found in the product label and described in the adult population or are not unexpected
for the patient population. One case reported the unlabeled event glomerulonephritis coincident
with filgrastim and pegfilgrastim, however, multiple medications and comorbidities, including
inflammator~ bowel disease,1,2 as well as recurrent infections coincident with chronic cyclic
neutropenia provide a plausible alterriative etiology.
. Two cases reported death as an outcome. One case was attributed to cardiac arrest secondary
to compression of the aortic arch by lymphadenopathy; the second lacked sufficient information to
assess the causal role of pegfilgrastim.
We did not identify any notable or unexpected safety concerns with pegfilgrastim use in pediatric
patients. DPV II will continue routine monitoring of adverse events with the use of pegfilgrastim in
pediatric patients.
1 BACKGROUND
1.1 PRODUCT FORMULATIONS AND INDICATIONS
Pegfilgrastim is supplied in the U.S. às:
6 mg per 0.6 mL in single use prefied syringe
Pegfilgrastim is approved for the following indication:
Neulasta is indicated to decrease the incidence of infection, as manifested by febrile
neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-
cancer drugs associated with a clinically significant incidence of febrile neutropenia.
Neulasta is not indicated for the mobilization of peripheral blood progenitor cells for
hematopoietic stem cell transplantation.
1 Takemura T, Okada M, Yagi K, Kuwajima H, Yanagida H. An adolescent with IgA nephropathy
and Crohn disease: pathogenetic implications. Pediatr Nephrol 2002; 17:863-6.
2 Filiopoulos V, Trompouki S, Hadjiyannakos D, Paraskevakou H, Kamperoglou D, et at. IgA
nephropathy in association with Crohn's disease: a case report and brief review of the literature.
Ren Fail 2010; 32(4):523-7.
3 Dale DC, Cottle TE, Fier CJ, Bolyard AA, Bonilla MA, et al. Severe Chronic Neutropenia:
Treatment and Follow-Up of Patients in the Severe Chronic Neutropenia International Registry
American Journal of Hematology 2003; 72:82-93.
i

4. 1.2 PEDIATRIC FILING HISTORY
Pegfilgrastim, a leukocyte growth factor (marketed by Amgen Inc.), received approval on 31
January 2002, to decrease the incidence of infection; as manifested by febrile neutropenia, in
patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated
with a clinically significant incidence of febrile neutropenia. As a condition of approval Amgen
committed to submit results from an ongoing study (990130) to evaluate the safety and efficacy of
pegfilgrastim in pediatric patients. On 14 November 2008, safety and pharmacokinetic data from
study 990130 was included in the Use in Specific Populations-Pediatric Use section of the labeL.
Study 990130 did not provide suffcient data to enable extrapolation of efficacy to the pediatric
population.
1.3 PEDIATRIC LABELING
The labeling for pegfilgrastim includes the following information concerning pediatric patients4.
Safety and effectiveness of Neulasta in pediatric patients have not been established. The
adverse reaction profile and pharmacokinetics of pegfilgrastim were studied in 37 pediatric
patients with sarcoma. The mean (:t standard deviation (SOl) systemic exposure (AUCo-in&
of pegfilgrastim after subcutaneous administration at 100 meg/kg was 22. a (:t 13.1)
mcg.hr/mL in the 6 to 11 years age group (n = 10), 29.3 (:t 23.2) mcg'hr/mL in the 12 to 21
years agé group (n = 13), and 47.9 (:t 22.5) mcg'hr/mL in the youngest age group (0 to 5
years, n = 11). The terminal elimination half-lives of the corresponding age groups were
20.2 (:t 11.3) hours, 21.2 (:t 16.0) hours, and 30.1 (:t 38.2) hours, respectively. The most
common adverse reaction was bone pain.
2 METHODS AND MATERIALS
2.1 AERS SEARCH CRITERIA
We searched the FDA's Adverse Event Reporting System (AERS) database for reports matching
the following criteria:
. Drug terms: Active ingredient (pegfilgrastim) and trade name (Neulasta)
. Medical Dictionary for Regulatory Activities (MedDRA) terms: All terms
. Time period: FDA received dates from 31 January 2002 to 31 August 2010
. Age ranges: all ages and 0 to 16 years
The AERS search retrieved a total of 3641 adverse event reports for pegfilgrastim (crude counts,
see Section 3.1). Twenty-seven reports involved pediatric patients ages 0 to 16 years. Of the 27
reports, two were duplicates and one (ISR 6930600) was an incorrectly
submitted/coded adult
patient. Therefore, we assessed 24 unique pediatric cases in this pediatric safety review.
4 Neulasta (pegfilgrastim) injection, for subcutaneous use Product Label, Amgen Inc., February
2010
2

5. 3 AERS RESULTS FOR PEGFILGRASTIM
3.1 CRUDE COUNTS OF ALL AERS REPORTS
Table 1 presents crude counts of AERS reports with pegfilgrastim from U.S. approval (31 January
2002) to 31 August 2010.
All reports (US)2 Serious3 (US) Death (US)
Adults(~17 rs.)
Pediatrics (0-16 rs.)
A e unknown (Null values)
Total
1 May include duplicates
2 US counts in parentheses
3 Serious adverse drug experiences per regulatory definition (CFR 314.80) include outcomes of
death, life-threatening, hospitalization (initial or prolonged), disability, congenital anomaly and other
serious important medical events.
2444 (1527)
27 (21)
1170 (773)
3641 (2321)
1955 (1063)
22 (16)
695 (321)
2672 (1400)
209 (102)
2 (1)
66 (26)
277 (129)
Figure 1 depicts the number of pediatric AERS reports with pegfilgrastim received per year from
US approval (31 January 2002) to 31 August 2010.
Figure 1: Number of Pediatric AERS Reports with
Pegfilgrastim by Year from U.S. Approval Date (31 January
2002) to 31 August 2010
5
4
3
AERS Reports
2
1
o
1-# Peds Reports I
~~~~~~~~~oooOOOOOOOCDO..NW,i01cn..
Year
3

6. 3.2 CHARACTERISTICS FROM PEDIATRIC SAFETY REVIEW
Table 3 describes the characteristics of the 24 pediatric AERS cases reported from U.S. Approval
(31 January 2002) to 31 August 2010.
Gender (n) Male:12
Female:12
0- -:1 month: 0
1 month -:2 yrs: 1
2-5 yrs: 3
6-11 yrs: 6
12-16 yrs: 14
Mean 11 ears; Median 14 ears
US 21, Forei n 3
1996: 1 2003: 4 2007: 1 2010: 1
2001: 1 2004: 4 2008: 1
2002: 1 2006: 2 2009: 4
Avera e 5 m ,Median 6 m
Median 1 day
Ran e 1 to 365 da s
Chemotherapy induced neutropenia 18; Severe Chronic
Neutropenia 5; neutropenia (NOS) 1
Death 2, Life-Threatening 3, Hospitalization 8
Disability 1, Other Medically Serious 5; Non-serious 5
Characteristics of the 24 individual pediatric cases is provided in Appendix A.
Ori in (n)
Event date (n=20)
Age (n)
Dose (subcutaneous) (n=22J
Duration of therapy (n=14)
Reasons for use (n)
Outcomes(n)
4 DlSCUSSION/SUMMARY OF PEDIATRIC CASES
The AERS search retrieved 27 reports of pediatric patients, ages 0 to 16 years. Of the 27 reports
two were duplicates and one (ISR 6930600) was an incorrectly submitted/coded adult patient.
We assessed 24 unique pediatric cases in this pediatric safety review.
4.1 DEATHS (N= 2)
Two cases had an outcome of death. One case attributed death to cardiac arrest (an unlabeled
event) secondary to compression of the aortic arch by lymphadenopathy and unrelated to
pegfilgrastim. The second case had insufficient information to assess the event. A summary of
these two cases is provided below.
1. ISR 5154157; Foreign; Expedited-15 day 2006; Cardiac Arrest
A 14-year-old female patient with metastatic squamous cell lung cancer received carboplatin
and docetaxel chemotherapy with pegfilgrastim support (6 mg subcutaneously). The patient
developed noisy breathing within a few hours of commencing pegfilgrastim, went into cardiac
arrest the same day, and died. The patient had no previous episodes of cardiac arrest but
had masses on the aortic arch. The patient's lung function prior to pegfilgrastim
administration was not reported. The patient appeared to be well following pegfilgrastim, with
no signs or symptoms other than the noisy breathing. An autopsy was not performed but
subsequent investigations identified the cause of death to be cardiac arrest, with
compression of the aortic arch caused by massive mediastinal and hilar lymphadenopathy
4

7. the likely causative factor. The reporting physician felt that there was no possibility that the
cardiac arrest may have been caused by pegfilgrastim.
2. ISR 6641459; US; Direct 201.0
An 8 year old female patient with malignant neoplasm of connective and other soft tissue
received pegfilgrastim2 mg subcutaneously 24 hours after chemotherapy (not otherwise
specified (NOS)) over a period of 120 days and died.
Reviewer's comment:
On 7 October 2010, this evaluator spoke with the reporter who stated it is their policy to
submit a MedWatch form for any patient that expires, regardless of drug association. The
reporter had phoned the patient's home prior to dispensing the next dose(s) of pegfilgrastim
and was informed the patient was deceased. No additional information was provided.
4.2 ALLERGIC-TYPE EVENTS (N=4)
Four cases reported allergic-type events occurring within 48 hours of the first dose of
pegfilgrastim. All events resolved with medication. No patients were rechallenged. The current
labeling appropriately reflects the postmarketing experience with allergic-type events (see
Warnings and Precautions and Adverse Reactions - Postmarketing Experience). A summary of
these four cases is provided below.
1. ISR 3962378- A 16 year old female with Hodgkin's disease, tape allergy, and a history of
a bee sting 2-3 days previous received adriamycin, bleomycin, vinblastine and
dacarbazine followed by the initial injection of pegfilgrastim 6 mg. She developed a wheal
at the injection site which progressed to a generalized rash and hives. The patient was
hospitalized and stabilized with epinephrine, dexamethasone, and diphenhydramine. The
patient then developed shortness of breath (oxygen sáturation of 70%), hypotension(BP
"60"), chest pain, tachycardia, nausea and vomiting. Epinephrine was re-administered
and all symptoms except flushing resolved. Treatment with methylprednisolone and
diphenhydramine continued.
2. ISR 6413084- A 15 year old male with acute lymphocytic leukemia received the initial
injection of pegfilgrastim 6mg without complications. Approximately 6 hours later he
complained of itching and the mother noticed large welts on his abdomen and legs and
administered diphenhydramine. Upon arrival to the hospital the hives had spread to
upper body and face. He was hospitalized and stabilized with epinephrine and steroids.
All symptoms resolved within 24 hours.
3. ISR 6244513- A 6 year old female received an initial injection of pegfilgrastim 2 mg for
neutropenia (NOS). She experienced headache, generalized erythema, dyspnea,
hypotension and vomiting after the medication. Treatment included hydrocortisone,
acetaminophen and epinephrine. The events resolved.
4. ISR 4656582- A 14 year old male with pelvic malignancy (NOS) received vincristine,
doxorubicin, cyclophosphamide followed by an initial injection of 6 mg pegfilgrastim. He
developed an injection site reaction characterized as localized, warm raised erythema 48
hours after pegfilgrastim administration. Treatment included cetirizine, diphenhydramine,
and warm compresses. All symptoms resolved within 5 days. Pegfilgrastim was
discontinued and filgrastim was administered with subsequent cycles of chemotherapy
without recurrence of the event.
4.3 MISCELLANEOUS EVENTS IN THE UNLABELED INDICATION SEVERE CHRONIC NEUTROPENIA (N=5)
Five cases involved pediatric patients with a variant of Severe Chronic Neutropenia, i.e.,
autoimmune, chronic cyclic, congenital, and severe congenital (n=2). Most events reported in
these cases are not unexpected for the drug or the patient population and are labeled.
5

8. Three cases had an outcome of hospitalization; however, hospitalization occurred because of
febrile neutropenia (n=2) or febrile infection (n=1). A summary of these three cases is provided
below.
1. ISR 4412170- The 15 year old female was hospitalized for jaw abscess with fever and
experienced leucocytosis (135,900/mm a labeled event, 3 days following pegfilgrastim
administration. Leucocytosis could have also been influenced by the concurrent infection.
Leucocytosis resolved in 4 days and she continued on pegfilgrastim.
2. ISR 67106095- The 2 year old male was hospitalized for febrile neutropenia and
erroneously received 6 mg pegfilgrastim instead of 100 mcg/kg, a 937 mcg/kg overdose.
He was discharged on day 11 without clinical sequela, and resumed daily filgrastim.
3. ISR 4242771- The 10 year old female was hospitalized for febrile neutropenia following
11 months of uneventful pegfilgrastim therapy (6 mg every 14 days). Three weeks
following hospital discharge she was again hospitalized for febrile neutropenia with
complaints of headache and "abnormal sensation of the tongue." She recovered and
resumed pegfilgrastim but at weekly intervals (6 mg every 7 days).
Of the remaining two cases, one was medically serious, however, multiple medications and
comorbidities, including inflammatory bowel disease,1.2 as well as recurrent infections coincident
with chronic cyclic neutropenia3 provide plausible alternative etiology. The remaining case was
non-serious. A summary of these two cases is provided below.
1. ISR 4170505- A 15 year old male with depression, persistent anemiå, normal bone
marrow biopsy, colon resection for typhlitis and multiple medical problems (NOS)
experienced glomerulonephritis coincident with filgrastim. Prednisone, mycophenolate
and a 12-month pulse regimen of methylprednisolone were administered with
improvement in signs and symptoms over the following 9 months. Prednisone taper
resulted in a flare in signs and symptoms. Filgrastim was discontinued and pegfilgrastim
6 mg every 23 days was initiated. He required several dose and frequency adjustments
to prednisone and methylprednisone pulse therapy while on pegfilgrastim. Titers for
neutralizing antibodies to filgrastim or pegfilgrastim were negative; renal biopsy
performed at the onset of the event compared to the biopsy performed 19 months later
were similar and both showed endothelial and mesangial immune complexes.
2. ISR 5279067- A 7 year old male experienced declining response to filgrastim after 2
years which lead to filgrastim discontinuation. Filgrastim was re-started some time later
challenged with declining response after a year despite escalating doses. He was then
started on pegfilgrastim and experienced declining response after a year. The disposition
of pegfilgrastim was not provided.
5 CONCLUSIONS
Among the 24 unique pediatric cases, we observed the following:
. All but one of the pediatric cases reported adverse events that are qualitatively similar to those
currently found in the product label and described in the adult population or are not unexpected
for the patient population. One case reported the unlabeled event, Glomerulonephritis, coincident
with filgrastim and pegfilgrastim, however, multiple medications and comorbidities, including
inflammator~ bowel disease, 1.2 as well as recurrent infections coincident with chronic cyclic
neutropenia provide a plausible alternative etiology.
. Two cases reported death as an outcome. One was attributed to cardiac arrest secondary to
compression of the aortic arch by lymphadenopathy; the second lacked sufficient information to
assess the causal role of pegfilgrastim.
5 Dufour C, Cappelli B, Calvillo M, Fioredda F. et al. Similar favorable outcome of pegfilgrastim
overdose in patients with different age and underlying disease. Haematologica 2010; 95: 684-5.
6

9. . Four cases reported allergic-type events, including one event of Anaphylactic Reaction and one
event of Urticaria both requiring emergency treatment and hospitalization. The current labeling
appropriately reflects the postmarketing experience with allergic-type events (see Warnings and
Precautions and Adverse Reactions - Postmarketing Experience).
. Five cases involved miscellaneous events in patients with a variant of Severe Chronic
Neutropenia, which is an unlabeled indication. Most events reported in these cases are not
unexpected for the drug or the patient population and are labeled. One of these five cases
included the adverse event Glomerulonephritis discussed above.
. Two cases reported Accidental Overdose (one serious), wherein each patient received the 6 mg
adult dose in error. Both patients recovered without clinical sequela. These cases are under
review by the Division of Medication Error Prevention and Analysis.
6 RECOMMENDATIONS
Because we did not identify any notable or unexpected safety concerns with pegfilgrastim use in
pediatric patients, we do not have any recommendations at this time. DPV II will continue routine
monitoring of adverse events with the use of pegfilgrastim in pediatric patients.
7 APPENDICES
Appendix A: Line listing of AERS cases associated with the use of pegfilgrastim in children 0-16
years old, received by the FDA from U.S. approval (31 January 2002) to 31 August 2010 (n=24).
7

10. 7.1ApPENDIXA:LINELISTINGOFAERSCASESASSOCIATEDWITHTHEUSEOFPEGFILGRASTIMINCHILDREN0-16YEARSOLD,RECEIVEDBYTHEFDA
FROMU.S.APPROVAL(31JANUARY2002)TO31AUGUST2010(N=24)
5154157Expedited
I
14/F
iDE
aorticocclusion,cardiac.iNeulasta,Carboplatin,
IChemotherapy
I6mgonce
(15-Day)/GBarrest,hilarlymphadenopathy,Docetaxel(squamouscell
lymphadenopathymediastinalcarcinomaofthe
lung)
6641459IDirect/USI9/FIDEideathiNeulasta,NoOther
ChemotherapyI2mgI120
MedicationsProvided(neoplasmof
connectiveandother
soft
3962378Expedited
I
16/F
ILT,HOIanaphylacticreaction
Neulasta,Doxorubicin,mgonce
(15-Day)/USBleomycin,Vinblastine,
i(Hodgkin'sDacarbazinelymphoma)
4170505Expedited
I
151M
iOTIbloodalbumindecreased,
Neulasta,Neupogen,
IChronicSevere
6mgq23days270
(15-Day)/USdrugspecificantibodySomatropin,IronNeutropenia(chronic(ongoing)
present,focalsegmentalSulfatethiaminCompoundcyclicneutropenia)
glomerulosclerosis,Tab,FolicAcid,Sertraline
glomerulonephritisrapidly
progressive,
hypocomplementaemia,lupus
nephritis,whitebloodcells
urinepositive
4172701IDirect/USI16/FiDSdysstasia,gaitdisturbance,Vincristine,Neulasta,ChemotherapyI6mgq25days
neurotoxicity,peronealnerveDoxorubicin,Bleomycin,(hodgkin's
palsyEtoposide,Prednisone,lymphoma)
Cyclophosphamide,
Neupogen
4238697Expedited131MHOdrugineffective,febrileNeulasta,NoOtherChemotherapy4.5mgUNK
(15-Day)/USneutropeniaMedicationsReported(osteosarcoma)
4242771Expedited10/FHOdiseaserecurrence,febrileNeulasta,ConcertaChronicSevere6mgq14days330
(15-Day)/USneutropenia,headache,Neutropeniaincrease
hypoaesthesiaoral(autoimmunefrequencytoq
neutropenia)7days
(ongoing)

11. 4258824Expedited
I
151M
IHOIescherichiasepsis,febrile
Neulasta,Cytarabine,
iChemotherapy
i6mgonce
(15-Day)/USneutropenia,septicshockAsparaginase,Fluticasone(acutelymphoid
Propionate,Fexofenadine,leukemia)
Trimethoprim-
SuIfamethoxazole,Methotrex
ate,Doxorubicin,Vincristine,
Vancomycin,Tobramycin,
Meropenem
4382430Expedited
181MILT,HO
febrileneutropenia,abdominalNeulasta,Neurontin,
IChemotherapy
I2mgonce
(15-Day)/USdistension,enterocolitis,Clotrimazole,Oxycodone,(Ewing'ssarcoma)
tachycardia,tachypnoea,Senokot,Tylenol,
atelectasis,clostridialVancomycin,Meropenem,
infection,pleuraleffusionNilstat,Flagyl,Benadryl,
Ondansetron,Cefepime,
Septra,Ativan,Ambisome,
Vincristine,Doxorubicin,
Cyclophosphamide
4412170IExpedited
I
15/F
IHO
febrileinfection,leukocytosis,
INeulasta,Amoxicillinand
ChronicSevere6mgq14days365
(15-Day)/UScellulitis,abscessjawc1avulanatepotassium,Neutropenia(ongoing)
Ceftriaxonesodium,
Vancomycin
4506566/4515088IExpedited
I
16/F
ILT,HOifebrilebonemarrowaplasia,
¡IfOSfamide,Mesna,ChemotherapyI6mgonce
(15-Day)/USconfusionalstate,Etoposide,Carboplatin,(nephroblastoma)
electroencephalogramNeulasta,
abnormal,hallucination,
tremor
4650551Expedited
I
15/F
lOTIanaemia,deafness,disease
Cisplatin,Paclitaxel,Chemotherapy(renal6mgUNK
(15-Day)/USprogression,hepaticGemcitabine,Neulasta,medullarycarcinoma)
neoplasmmalignantrecurrent,Carboplatin,Methotrexate,
hypokalaemia,Vinblastine,Doxorubicin
hypomagnesaemia,
hypophosphataemia,nausea,
nephropathytoxic,
neutropenia,thrombocytopenia
5126952Expedited
i4.5/MiHO,OT
pyrexia,febrileneutropenia,Neulasta,Ara-C,ChemotherapyI2.4mgonce
(15-Day)/USblastcells,blastcellspresent,Asparaginase,Miralax,(lymphocytic
shifttotheleftMorphine,Zantac,Zofran,leukemia)
Senna
541348315428044IExpedited
131MiOT
leukocytosisNeulasta,Temozolomide,Chemotherapy3mgIUNK
(15-Day)/USEtoposide,(medulloblastoma)
Cyclophosphamide,Mesna,
Vincristine,Filgrastim
2

12. 3