Medicinal Products

DACOGEN 50 mg

Generic drug of the therapeutic class: Oncology and Hematology
active ingredients: Decitabine
laboratory: Janssen Cilag Internat NV

Powder for concentrate for solution for infusion IV
Box of 1 vial of 50 mg
All forms

Indication

Dacogen is indicated for the treatment of adult patients 65 years of age and older with acute myeloid leukemia (AML) as defined by the World Health Organization (WHO), newly diagnosed, de novo or secondary, and not candidates for standard induction chemotherapy.

Dosage DACOGEN 50 mg Powder for concentrate for solution for infusion IV Box of 1 vial of 50 mg

Administration of Dacogen should be initiated under the supervision of a physician experienced in the use of chemotherapeutic agents.


Dosage

During a treatment cycle, Dacogen is administered at a dose of 20 mg / m 2 of body surface area per 1 hour intravenous infusion repeated daily for 5 consecutive days (i.e., a total of 5 doses per treatment cycle). The total daily dose should not exceed 20 mg / m 2 and the total dose per treatment cycle should not exceed 100 mg / m 2 . If a dose is missed, treatment should be resumed as soon as possible. The cycle should be repeated every 4 weeks depending on the clinical response of the patient and the observed toxicity. It is recommended that patients be treated with a minimum of 4 cycles; however, obtaining complete or partial remission may take more than 4 cycles. The treatment can be continued as long as the patient shows a response, a benefit or has a stable disease, that is to say without clear progression.

If after 4 cycles, the hematological values ​​of the patient (such as platelet count or neutrophil counts) have not returned to pre-treatment values ​​or if the disease progresses (increased number of peripheral blasts or increased blasts in the bone marrow), the patient may be considered non-responders and alternative therapeutic options to Dacogen should be considered.

Premedication to prevent nausea and vomiting is not recommended routinely but can be given if needed.

Management of myelosuppression and related complications

Myelosuppression and adverse events related to myelosuppression (thrombocytopenia, anemia, neutropenia, and febrile neutropenia) are common in patients with AML treated or untreated. Complications of myelosuppression include infections and bleeding. The attending physician may decide to delay treatment if the patient has complications related to myelosuppression, such as those described below:

• Febrile neutropenia (temperature ≥ 38.5 ° C and neutrophils count

<1000 / μL)

• Active viral, bacterial, or fungal infection (that is, requiring intravenous anti-infectives or significant symptomatic treatment)

• Haemorrhage (gastrointestinal, genitourinary, pulmonary with a number of platelets

<25, 000 / μL or any hemorrhage from the central nervous system)

Treatment with Dacogen may be resumed once these conditions have improved or been stabilized by appropriate treatment (anti-infective therapy, transfusions, or growth factors).

In clinical studies, approximately one third of patients receiving Dacogen required a dose delay. A decrease in the dose is not recommended.

Pediatric population

The safety and efficacy of Dacogen in children under 18 years of age have not been established. No data available.

Hepatic insufficiency

No studies have been conducted in patients with hepatic impairment. The need for dose adjustment in patients with hepatic impairment has not been evaluated. If hepatic function worsens, patients should be closely monitored (see Warnings and Precautions and Pharmacokinetic Properties sections).

Renal failure

No studies have been conducted in patients with renal impairment. The need for dose adjustment in patients with renal impairment has not been evaluated (see sections Warnings and Precautions and Pharmacokinetic Properties ).


Administration mode

Dacogen is given as an intravenous infusion. A central venous catheter is not required. For instructions on reconstitution and dilution of the drug before administration, see Instructions for Use, Handling and Disposal .

Against indications

Hypersensitivity to decitabine or to any of the excipients listed under section.
Breast-feeding (see section Pregnancy and breast-feeding ).

Dacogen side effects

Tolerance Profile Summary

The most common (≥35%) adverse reactions reported during treatment with Dacogen are: pyrexia, anemia and thrombocytopenia.

The most common Grade 3/4 adverse events (≥ 20%) included pneumonia, thrombocytopenia, neutropenia, febrile neutropenia and anemia.

In clinical studies, 30% of patients treated with Dacogen and 25% of patients treated in the comparator arm had adverse effects with a fatal outcome during treatment or within 30 days after the last dose of experimental drug.

In the Dacogen arm, there was a greater incidence of treatment discontinuation due to adverse effects in women than in men (43% versus 32%).


Table listing adverse effects

The adverse reactions reported in 293 AML patients treated with Dacogen are summarized in Table 1. The table below reflects data from clinical studies conducted in AML. Adverse effects are presented by frequency category. Frequency categories are defined as follows: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1 / 10, 000 to 1 <1, 000), very rare (<1 / 10, 000).

Within each frequency category, adverse effects are presented in order of decreasing severity.

Table 1: Adverse Reactions Identified with Dacogen

Body Systems Class

Frequency

(all grades)

Undesirable effect

Frequency

All grades

(%)

Grades 3-4 to (%)

Infections and infestations

Very common

pneumonia*

24

20

urinary tract infection *

15

7

Frequent

septic shock*

6

4

sepsis *

9

8

sinusitis

3

1

affections

hematologic and lymphatic system

Very common

febrile neutropenia *

34

32

neutropenia *

32

30

thrombocytopenia b *

41

38

anemia

38

31

leukopenia

20

18

Rare

pancytopenia *

<1

<1

Immune system disorders

Frequent

hypersensitivity including anaphylactic reaction c

1

<1

Nervous system disorders

Very common

cephalalgia

16

1

Respiratory, thoracic and mediastinal disorders

Very common

epistaxis

14

2

Gastrointestinal disorders

Very common

diarrhea

31

2

vomiting

18

1

nausea

33

<1

Frequent

stomatitis

7

1

Skin and subcutaneous tissue disorders

Rare

acute febrile neutrophilic dermatosis (Sweet's syndrome)

<1

N / A

General disorders and administration site conditions

Very common

pyrexia

48

9

a Grades the most severe according to the classification "National Cancer Institute Common Criteria Terminology for Adverse Events"

b Including hemorrhage associated with thrombocytopenia, including fatal outcome

c Including "preferred tarnished" hypersensitivity, hypersensitivity to the drug, anaphylactic reaction, anaphylactic shock, anaphylactoid reaction, anaphylactoid shock

* Includes events with a fatal outcome

NA = Not applicable


Description of particular adverse effects


Hematologic side effects

The most commonly reported hematologic adverse events associated with Dacogen therapy included febrile neutropenia, thrombocytopenia, neutropenia, anemia, and leukopenia.


Serious adverse events related to infection such as septic shock, sepsis and pneumonia have been reported in patients receiving Dacogen.


Serious bleeding-related adverse events, some of which led to death, such as central nervous system (CNS) haemorrhage (2%) and gastrointestinal bleeding (GI) (2%), in the context of thrombocytopenia severe, have been reported in patients receiving Dacogen.


Hematologic adverse reactions should be managed by routine monitoring of the blood count and early administration of symptomatic treatment as needed. Symptomatic treatments include administration of prophylactic antibiotics and / or growth factors (eg G-CSF) for neutropenia and transfusions for anemia or thrombocytopenia in accordance with institutional recommendations. For situations where the administration of decitabine should be delayed, see section Dosage and method of administration .

Popular Posts

Category Medicinal Products, Next Article