Choice for Myelodysplastic

Syndrome and Acute Myeloid

Leukemia
Product Information

Dacogen (decitabine) is a cytosine nucleoside analogue that

selectively inhibits DNA methyltransferases at low dose,
resulting in gene promoter hypomethylation that can result in
reactivation of tumor suppressor genes, induction of
cellular differentiation or cellular senescence followed by
programmed cell death.

Dacogen product information 2019

Indication of DACOGEN

MYELODYSPLAS ACUTE
TIC SYNDROME MYELOID
(MDS)
Previously treated and previously untreated
LEUKAEMIA
Adult patients aged 65 and above with
(AML)
newly diagnosed de novo or secondary
De novo MDS and Secondary MDS of all
FAB subtypes AML according to WHO classification
Intermediate -1, Intermediate- 2, and High (who are not candidates for standard
Risk International Prognostic Scoring
System groups induction chemotherapy)

Dacogen product information 2019

 DACOGEN GIVES LONGER TERM OUTCOME IN MDS TREATMENT AT MEDIAN
REMISSION DURATION 20 MONTHS AND MEDIAN SURVIVAL 22 MONTHS
Update of the Decitabine experience in higher risk Myelodysplastic Syndrome and analysis of prognostic factors associated with outcome

• One hundred fifteen patients with higher risk MDS who received treatment
with decitabine were reviewed.
• Patients received decitabine 100 mg/m2 per course every 4 weeks in 3
different schedules: 1) 20 mg/m2 intravenously daily x 5, 2) 20 mg/m2
subcutaneously daily x 5, and 3) 10 mg/m2 intravenously daily x 10.
Decitabine was given for a median of ≥7 courses (range, 1–23 courses).

Showed a favorable longer term outcome in patients with higher

risk MDS (median remission duration 20 months, median survival
22 months).

70%
Patient achieve
35%
Patient achieve
Overall Response Complete Response
Rate
Kantarjian, Hagop et al. 2007. Update of the Decitabine Experience in Higher Risk Myelodysplastic Syndrome and Analysis of Prognostic Factors Associated With Outcome.
 Extramedullary side effects in 115 patients included:
1. grade 1 and 2 fatigue in 5% of patients,

2. bone aches grade 1 and 2 in 10% of patients and grade 3 and 4 in 4% of

patients;

3. transient liver dysfunction grade 1 and 2 in 11% of patients and grade 3 and
4 in 4% of patients,

4. skin rashes grade 1 and 2 in 1% of patients,

5. nausea and emesis grade 1 and 2 in 17% of patients,

6. diarrhea grade 1 and 2 in 2% of patients,

7. other grade 1 and 2 side effects in 11% of patients

Myelosuppression- associated side effects in 967 courses were :

ADVERSE EVENTS 1. fever of unknown origin in 3% of courses,

OF 2. documented bacterial infections in 4% of courses,

3. pneumonias in 2.5% of courses,

DACOGEN
4. confirmed or suspected fungal infections in 0.7% of courses
IN MDS PATIENTS
5. grade 1 and 2 bleeding in 5% of courses, and

6. grade 3 and 4 bleeding in 1% of courses.

Hospitalization for complications was required in 14% of courses. With a

median of ≥ 7 courses, 39 of 115 patients (34%) never required any
hospitalization. Mortality was very low in the first 3 months and was
attributed mostly to myelosuppression-related complications or disease
progression.
Kantarjian, Hagop et al. 2007. Update of the Decitabine Experience in Higher Risk Myelodysplastic
Syndrome and Analysis of Prognostic Factors Associated With Outcome.
 DACOGEN GIVEN ON 5 DAY SCHEDULE PROVIDE LESS TOXICITY THAN 3
DAY SCHEDULE
Incidence and risk of hematologic toxicities with hypomethylating agents in the treatment of myelodysplastic syndromes and acute myeloid
leukopenia

• A total of 2337 MDS or AML patients from 14 studies were identified in this meta-
analysis. Relevant studies were identified from PubMed, Embase, Cochrane
Library, and Clinical Trials .gov bases incepted to February 2018.
• The overall incidence of high grade hematologic toxicities in patients who received
HMAs were: 27% of patients anemia, 45% with neutropenia, 38% with
thrombocytopenia, and 25% with febrile neutropenia respectively

Suggested that decitabine at 100 mg/m2/course dosing regimen had

a greater clinical benefit in treating MDS than decitabine at 60 to
75 mg/m2/course and 135 mg/m2/course regimens.

Gao,Chong et al. 2018. Incidence and Risk of Hematologic Toxicities with Hypomethylating Agents in the Treatment of Myelodysplastic Syndromes and Acute AML: A Systematic Review and
Meta Analysis. Medicine
 Hematological Benefits

Transfusion independence was After

cycle 3
found to increase progressively MDS
with each cycle of decitabine Regiments
treatment
3 Day Dosing

Little change was noted in the

transfusion requirements for
patients receiving supportive care.
44 (of 89 MDS patients) become independent
over red blood cell transfusion

Kantarjian et al., 2006. Decitabine Improves Patient Outcomes in Myelodysplastic Syndromes: Results of a Phase III Randomized Study. American Cancer Society
IMPROVED RESPONSE IN AML TREATMENT WITH DACOGEN (CR 15.7)%
COMPARED TO TREATMENT OF CHOICE (7.4%)

Randomized, open-label, phase 3 study to compare the efficacy and safety of decitabine with patient’s treatment
choice under physician’s advice, either supportive care (SC) or cytarabine, specifically in older AML patients.
TC
Supportive Cytarabine Total TC Decitabine
Care (n=28) (n=125) (n=243) (n=242)
Response no % no % no % no %
CR 1 3.6 17 7.9 18 7.4 38 15.7
Dacogen improves Cri 1 3.6 6 2.8 7 2.9 24 9.9
response rate
CRp 0 0 1 0.5 1 0.4 5 2.1
in elderly patients with
newly diagnosed AML CR+CRp 1 3.6 18 8.4 19 7.8 43 17.8
PR 1 3.6 8 3.7 9 3.7 6 2.5
Stable Disease 3 10.7 52 24.2 55 22.6 67 27.7
Progressive Disease 10 35.7 69 32.1 79 32.5 50 20.7
Not evaluable 12 42.9 63 29.3 75 30.9 57 23.6

Abbreviations: CR, complete remission; Cri, complete remission with incomplete blood count recovery; CRp,
complete remission with incomplete platelet recovery; TC, treatment choice

Kantarjian H, et al. J Clin Oncol 2012;30:2670-7

DACOGEN ALSO SHOWS COMPARABLE TOLERABILITY WITH
CYTARABINE

randomized, open-label, phase 3 study to compare the efficacy and safety of decitabine with patient’s treatment
choice under physician’s advice, either supportive care (SC) or cytarabine, specifically in older AML patients

Treatment-Emergent Adverse Events of Grades 3 or 4 in ≥10%

of Patients in Any Group (2009 clinical cutoff)

AE reports are similar Supportive Care Cytarabine Total TC Decitabine

between Decitabine and (n = 29) (n = 208) (n = 237) (n = 238)
Cytarabine, while Adverse Event No. % No. % No. % No. %
Decitabine patients
undergo median 4 cycles Any grade 3 or 4
16 65 188 90 204 88 221 93
vs 2 cycles of treatment adverse event
choice (TC) Thrombocytopenia 4 14 73 35 77 32 95 40
Anemia 4 14 56 27 60 25 80 34
Febrile neutropenia 0 0 51 25 51 22 76 32
Neutropenia 1 3 41 20 42 18 76 32
Leukopenia 0 0 20 10 20 8 47 20
Pneumonia 4 14 39 19 43 18 51 21
Bronchopneumonia 3 10 9 4 12 5 10 4
Disease progression 2 7 46 22 48 20 43 18
General physical
health 5 17 33 16 38 16 30 13
deterioration
* TC (treatment choice): supportive care (SC) or cytarabine(20mg/m2
SC for 10 consecutive days every 4 weeks)

Kantarjian H, et al. J Clin Oncol 2012;30:2670-7

 PRODUCT INFORMATION

Pharmaceutical Form
20 mL single dose vial contains 50 mg of decitabine.

Administration
Intravenously by infusion.

final drug
concentration of
0.15-1.0 mg/mL. 2-8oC

Aseptically reconstituted Immediately after it, solution Unless used within 15

with 10 mL of sterile should be diluted with 0.9% minutes, solution must be
water for injection. NaCl or 5% dextrose prepared and stored at 2-8oC
injection. up to 4 hours until
administration.

Dacogen product information 2019

DOSE CALCULATION AND RECONSTITUTION SCHEME

Dose: 20 mg/m2 BSA 50 mg of Dacogen is aseptically

Amount of reconstituted with 10 mL of sterile
Dacogen needed is water for injection in the bottle
For example, BSA= 1.5 30 mg
m2
Q. How many mL
should be loaded?
A. 30 mg : 5 mg/mL Final concentration in the bottle = 5 mg/mL,
Total volume in the bottle = 10 mL

6 mL (water + Dacogen) in the syringe

If reconstituted to 100 mL kolf NaCl or D5, Still within range 0.15-1.0

the final concentration is 0.3 mg/mL mg/mL

Adapted from PI Dacogen 2019

5 Days Dosing: MDS Treatment

Dose:
20 mg/m2 body surface area
by IV infusion

Total daily dose must not exceed 20 mg/m2 and total dose per treatment cycle must not
exceed 100 mg/m2

I hour I hour I hour I hour I hour

Day 1 Day 2 Day 3 Day 4 Day 5

Repeated every
4 weeks
depending on clinical response and toxicity

If a dose is missed, treatment should be resumed soon. It is

recommended that patients be treated for a minimum 4 cycles
however a response might take longer than 4 cycles.
Dacogen product information 2019
5 Days Dosing: AML Treatment

Dose:
20 mg/m2 body surface area
by IV infusion
Total daily dose must not exceed 100 mg/m2.

I hour I hour I hour I hour I hour

Day 1 Day 2 Day 3 Day 4 Day 5

Repeated every
4 weeks
depending on clinical response and toxicity

If a dose is missed, treatment should be resumed soon. It is

recommended that patients be treated for a minimum 4 cycles
however a response might take longer than 4 cycles.
Dacogen product information 2019
Toxicities Management

Manifestation of Myelosuppression
Thrombocytopenia, anemia, neutropenia, and febrile neutropenia
along with some complication (infections and bleeding).

In AML
Treatment may be delayed at discretion of the treating physician if the patient experience such as: febrile neutropenia
(temperature ≥ 38.5oC and absolute neutrophil count < 1000 µL), active viral/bacterial/fungal infection, hemorrhage
(GIT, genitourinary, pulmonary, with platelets < 25000 µL or any central nervous system). Treatment with Dacogen may
be resumed once these conditions have improved or stabilized with adequate treatment.

In 5 day dosing regiment for MDS

During the first 3 cycles, clinicians may administer concomitant antimicrobial prophylaxis until recovery of
granulocytes to above 500 µL. Consider also early administration of growth factors to prevent/treat infections. In the
setting of moderate thrombocytopenia, full dose treatment should be administered together with platelet transfusions in
case of bleeding events.

After 3 cycles, dose should be delayed if there is toxicities related to the treatment. If recovery requires more than 8
weeks, the patient should be discontinued from the treatment and assessed for disease progression within 7 days after
end of 8 weeks.

Dacogen product information 2019

Toxicities
Management
Non-Hematological
toxicity
Withheld Dacogen therapy until levels return to within normal range or baseline if patients
have these conditions.

Serum Liver Func Infection

tion
Creatinine Test

nine SGPT or Active viral or

Serum creati or total bilir ALT or bacterial infection
an
level more th /dL ub
than or eq in more that is not controlled
g
equal to 2 m u
times hig al to 2 by concomitant anti
he
upper lim r the infective therapy
it of
normal

Dacogen product information 2019

 WARNING AND PRECAUTIONS

Myelosupression
Myelosupression and its complication may exacerbated with
Dacogen treatment, however it is reversible. CBC and
platelet counts should be closely monitored and there will
be dose modification if needed.
Cardiac Disease
Safety and efficacy of Dacogen in severe congestive heart
failure and unstable cardiac disease has not been
established

Hepatic Impairment Pediatric

Hepatic function should also be monitored closely. Safety and effectiveness in pediatric patients
has not been studied

Renal Impairment
Has not been studied, so should be used cautiously in
patients with severe renal impairment

Dacogen product information 2019

 CONTRAINDICATION AND INTERACTION

CONTRAINDICATION
Hypersensitivity to decitabine or any excipients and
lactation
INTERACTION
No formal clinical drug interaction studies with
decitabine have been conducted.
There is a potential for interaction with other agents
that are activated by sequential phosphorylation and/or
metabolized by enzymes implicated in the inactivation
of decitabine. Decitabine and co-administered drug
shows no impact to each other on in-vitro data.

Dacogen product information 2019

 Handling Instructions
• Shelf life for unopened vial is 3 years
• Do not store above 25oC
• Unless used within 15 minutes of reconstitution, the diluted
solution must be prepared using cold infusion fluids (2-8 oC) and
stored at 2-8oC for up to maximum 4 hours until administration.
• Should not be infused through the same IV line with other
medicinal products

Dacogen product information 2019

HARUS DENGAN RESEP DOKTER
Please consult full product information before prescribing.
for adverse events (AE) reporting, please contact:
PT. Johnson and Johnson Indonesia
K-Link Tower
Jl. Jendral Gatot Subroto Kav. 59A – 12th floor
Jakarta Selatan 12950, INDONESIA
Telp (+62) 21 2935 3935
Email: drugsafety@jacid.jnj.com