Dacogen

[Drug name]

Common name: Decitabine for Injection

English name: Decitabine for Injection

Trade name: Dacogen®

[Ingredients]

Active ingredient: decitabine (5-aza-2'-deoxycytidylic acid)

Chemical name: 4-amino-1-(2-deoxy-β-D-erythro-ribofuranose)-1,3,5-triazine-2(1 H)-ketone

Molecular formula: C8H12N4O4

Molecular weight: 228.21

Excipients: potassium phosphate (potassium dihydrogen phosphate), sodium hydroxide

[Properties]

This product is a sterile, freeze-dried white powder and loose block.

[Indications]

Applicable to initially treated and re-treated patients with myelodysplastic syndrome (MDS) at intermediate risk -1, intermediate risk -2 and high risk in the IPSS scoring system, including primary and secondary MDS, all subtypes classified according to FAB : Refractory anemia, refractory anemia with ring sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts-transformed, chronic myelomonocytic leukemia.

[Specifications]

50mg

[Usage and Dosage]

First dosing cycle

The recommended dose of this product is 15mg/m2, continuous intravenous infusion for more than 3 hours, once every 8 hours, for 3 consecutive days. Patients can take conventional antiemetics beforehand.

Subsequent dosing cycles

A cycle is repeated every 6 weeks. It is recommended to repeat at least 4 cycles. However, patients who achieve complete or partial remission can be treated for more than 4 cycles. If the patient continues to benefit, the medication can be continued.

Dose adjustment or delayed administration based on hematological laboratory test values

If hematological recovery (ANC ≥ 1,000/μL, platelets ≥ 50,000/μL) requires more than 6 weeks after the previous cycle of treatment with this product, the treatment for the next cycle should be delayed, and the dose should be temporarily adjusted according to the following principles:

· Recovery time is more than 6 weeks but less than 8 weeks - the dosing of this product should be delayed by 2 weeks and treatment should be restarted at a dose reduced to 11 mg/m2 every 8 hours (33 mg/m2/day, 99 mg/m2/cycle):

Recovery time more than 8 weeks but less than 10 weeks - the patient should be evaluated for disease progression (by bone marrow aspiration). If no progression occurs, the dosing of this product should be delayed by more than 2 weeks and the dose should be reduced to 11 when restarted. mg/m2 every 8 hours (33 mg/m2/day, 99 mg/m2/cycle), then maintain or increase dose as clinically appropriate in subsequent cycles.

If any of the following non-hematological toxicities occur, suspend treatment with this product until the toxicity recovers: 1) Serum muscle tincture ≥ 2 mg/dL: 2) SGPT, total bilirubin ≥ 2 times ULN; 3) Active or uncontrolled infection.

Dose for elderly patients

The dosage for elderly patients is usually the same as that for adults. If toxicity occurs, the dosage should be adjusted according to the principles of the general population.

[Adverse reactions]

The following safety data mainly come from foreign clinical studies. Racial differences cannot yet be assessed because non-whites were not represented in sufficient numbers.

The most common adverse reactions

Neutropenia, thrombocytopenia, anemia, weakness, fever, nausea, cough, petechiae, constipation, diarrhea, and hyperglycemia.

In the Phase III clinical trial (D-0007), the most common (≥1%) adverse reactions requiring clinical intervention in the treatment group of this product

Withdrawal: thrombocytopenia, neutropenia, pneumonia, Mycobacterium avium complex infection, cardio-respiratory arrest, elevated blood bilirubin, intracranial hemorrhage, abnormal liver function.

Delayed administration: neutropenia, pulmonary edema, atrial fibrillation, central system infection, febrile neutropenia;

Dose reduction: neutropenia, thrombocytopenia, anemia, lethargy, edema, tachycardia, depression, pharyngitis.

[Contraindications]

This product is contraindicated in patients known to be allergic to decitabine.

[Precautions]

During the treatment of this product, neutropenia and thrombocytopenia will occur. Whole blood and platelet counts must be performed to monitor reactions and toxicity to ensure that at least the minimum limit is reached before each dosing cycle. After administration of the recommended dose in the first cycle, the dose administered in subsequent cycles should be adjusted as described in "Dosage and Administration." Physicians should consider early administration of growth factors and/or antimicrobials to prevent and treat infection.

Myelosuppression and neutropenia are more common in the first or second cycle of medication, but they do not necessarily mean the progression of the underlying disease MDS.

There is a lack of data on the use of this product in patients with liver and kidney dysfunction, so these people should use it with caution. Although metabolism is extensive, the cytochrome P450 enzyme system is not involved in metabolism. In clinical trials, this product is not used in patients with serum creatinine >2.0 mg/dL, transaminase exceeding 2 times the normal value, or serum bilirubin >1.5 mg/dL.

Information for patients

Patients should inform their physician of any underlying liver or kidney disease.

Women of childbearing age should be advised to avoid pregnancy during treatment with this product.

Male patients should also avoid giving birth during treatment with this product and within 2 months after treatment.

Laboratory Testing

Complete blood cell and platelet counts should be performed to monitor response and toxicity and ensure that at least minimum levels are achieved before each dosing cycle. Liver biochemistry and serum creatinine should be tested before initiating treatment.

Warning

Pregnancy-teratogenic effects: Pregnancy drug classification D

Male use

Male patients should be advised not to have children during treatment with this product and within 2 months after use.

[Drugs for pregnant and lactating women]

Pregnant women

Injection of this product into pregnant women may cause potential harm to the fetus. The developmental toxicity of decitabine was studied in mice, administered as a single intraperitoneal dose on days 8, 9, 10, or 11 of gestation. 0, 0.9 and 3.0 mg/m2], which are approximately 2% and 7% of the clinically recommended dose, respectively. No maternal toxicity was observed, but a decrease in embryonic survival rate was observed in the 3 mg/m2 dose group, and a decrease in fetal weight occurred at both dose levels. The 3 mg/m2 dose can cause fetal defects, including rib hyperplasia, fusion of vertebrae and ribs, cleft palate, spinal defects, hind limb defects, and lack of front and rear limbs (two dose levels). No maternal toxicity was observed when rats were given a single intraperitoneal dose of 2.4, 3.6 or 6 mg/m2 (approximately 5, 8 or 13% of the recommended clinical dose, respectively) on gestation days 9-12. No live fetuses were observed in either dose group after injection of decitabine on day 9 of gestation. On the 10th day of pregnancy, when doses of decitabine above 3.6 mg/m2 were given, the embryo survival rate or fetal weight decreased significantly. Vertebral and rib abnormalities occurred at all dose levels, and malformations such as exophthalmos, exencephaly, and cleft palate occurred at the 6.0 mg/m2 dose level. An increased incidence of embryonic predigital defects was observed at doses above 3.6 mg/m2. Shortening of the long bones and reduced ossification of the forelimbs was observed at the 6.0 mg/m2 dose.

Adequate and well-controlled clinical studies of this product have not been conducted in pregnant women. Women of childbearing potential should use contraceptive measures during treatment with this product. If treated with this product during pregnancy or if the patient becomes pregnant while taking this product, the patient should be informed of the potential harm to the fetus.

Lactating women

It is not known whether decitabine and its metabolites are excreted in breast milk. Because many drugs are excreted in breast milk, and because decitabine may cause serious side effects in a nursing infant, the decision to discontinue the drug should be weighed against its importance to the mother.

[Pediatric Medication]

The safety and effectiveness of the medication in pediatric patients have not been established.

[Drug for the Elderly]

In the Phase III clinical trial, 61 of the 83 patients treated with this product were 65 years old and above, and 21 were 75 years old and above. No differences in safety and efficacy were observed in these subjects compared with younger subjects, and other clinical uses have not confirmed different response rates between the elderly and young people, but the possibility of greater sensitivity in some older people cannot be ruled out.

[Drug Interactions]

Interactions between decitabine and other drugs have not been studied. In vitro studies using human liver microsomes suggest that decitabine is unlikely to inhibit or induce CYP450 enzymes. In vitro metabolism studies also suggest that decitabine is not a substrate for hepatic CYP450 enzymes. Because decitabine has negligible plasma protein binding (<1%), interactions due to highly protein-bound drugs displacing decitabine from plasma proteins are unlikely.

[Drug Overdose]

There is no known specific antidote for overdose of this product. High doses often exacerbate myelosuppression including neutropenia and thrombocytopenia. Appropriate supportive care should be taken in case of overdose.

[Storage]

Storage at 25℃ (77˚F): The allowable range is 15-30℃ (59-86˚F).

[Packaging]

Glass bottle, 1 bottle/box.

[Validity period]

36 months