Dacogen

Dacogen

Manufacturer:

Janssen

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Decitabine.
Description
Each 20 mL single dose vial contains 50 mg of decitabine.
After aseptic reconstitution with 10 mL of Sterile Water for Injection, each mL of the concentrate of solution for infusion contains 5 mg of decitabine.
Excipients/Inactive Ingredients: Monobasic potassium phosphate, Sodium hydroxide, Hydrochloric acid, Nitrogen, Water for injection.
Action
Pharmacotherapeutic Group: Antineoplastic and Immunomodulating Agent, Pyrimidine Analogues. ATC Code: L01BC08.
Pharmacology: Pharmacodynamics: Mechanism of Action: Decitabine (5-aza-2'-deoxycytidine) is a cytosine nucleoside analogue that selectively inhibits DNA methyltransferases at low doses, 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.
Clinical Studies: Clinical studies in MDS: Phase 2 Study (DACO-020): 5-Day Dosing Regimen: An open-label, single arm, multicenter study (DACO-20) was conducted to evaluate the efficacy of DACOGEN in MDS patients with any of the FAB subtypes. In this study, 99 patients with IPSS Intermediate-1, Intermediate-2, or high risk prognostic scores received DACOGEN by the 5-Day dosing regimen of 20 mg/m2 intravenous infusion over 1-hour daily, on Days 1 to 5 every 4 weeks (1 cycle). The results were consistent with the results of the Phase 3 study and summarized in Table 1. (See Table 1.)

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Phase 3 Study (D-0007): 3-Day Dosing Regimen: A randomized, open-label multicenter, controlled study (D-0007) evaluated DACOGEN in 170 subjects with MDS meeting FAB classification criteria and IPSS High Risk, Intermediate-2, and Intermediate-1 prognostic scores. DACOGEN was administered as the 3-Day dosing regimen of 15 mg/m2, by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 consecutive days of every 6-weeks cycle.
In the Phase 3 clinical study, CRs and PRs were seen across all IPSS subgroups. However, a greater beneficial effect was evident in the subgroups of patients classified as Int-2 and High Risk, see Table 2.

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Clinical studies in AML: The use of DACOGEN was studied in an open-label, randomized, multicenter Phase 3 study (DACO-016) in subjects with newly diagnosed de novo or secondary AML according to the WHO classification. DACOGEN (n=242) was compared to treatment choice (TC, n=243) which consisted of patient's choice with physician's advice of either supportive care alone (n=28, 11.5%) or 20 mg/m2 cytarabine subcutaneously once daily for 10 consecutive days repeated every 4 weeks (n=215, 88.5%). DACOGEN was administered as a 1-hour intravenous infusion of 20 mg/m2 once daily for 5 consecutive days repeated every 4 weeks. The median age for the intent-to-treat (ITT) population was 73 years (range 64 to 91 years). Thirty-six percent of subjects had poor-risk cytogenetics at baseline. The remainder of the subjects had intermediate-risk cytogenetics. The primary endpoint of the study was overall survival. The secondary endpoint was complete remission rate that was assessed by independent expert review. Progression-free survival and event-free survival were tertiary endpoints.
The median overall survival in the intent-to-treat population was 7.7 months in subjects treated with DACOGEN compared to 5.0 months for subjects in the TC arm (hazard ratio [HR] 0.85; 95% CI: 0.69, 1.04, p=0.1079). The difference did not reach statistical significance, however, there was a trend for improvement in survival with a 15% reduction in the risk of death for subjects in the DACOGEN arm (Figure 1). When censored for potentially disease modifying subsequent therapy (i.e., induction chemotherapy or hypomethylating agent) the analysis for overall survival showed a 20% reduction in the risk of death for subjects in the DACOGEN arm (HR=0.80; 95% CI: 0.64; 0.99, p-value=0.0437). (See Figure 1.)

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In an analysis with an additional 1 year of mature survival data, the effect of DACOGEN on overall survival demonstrated a clinically meaningful improvement compared to the TC arm (7.7 months versus 5.0 months, respectively, HR=0.82; 95% CI: 0.68, 0.99, nominal p-value=0.0373, Figure 2). (See Figure 2.)

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Based on the initial analysis in the intent-to-treat population, a statistically significant difference in complete remission rate (CR+CRp) was achieved in favor of subjects in the DACOGEN arm, 17.8% (43/242) compared to the TC arm, 7.8% (19/243); treatment difference 9.9% (95% CI: 4.07; 15.83), p=0.0011. The median time to best response and median duration of best response in patients who achieved a CR or CRp were 4.3 months and 8.3 months, respectively. Progression-free survival was significantly longer for subjects in the DACOGEN arm, 3.7 months (95% CI: 2.7; 4.6) compared with subjects in the TC arm, 2.1 months (95% CI: 1.9; 3.1); HR=0.75; 95% CI: 0.62; 0.91, p=0.0031. These results as well as other endpoints are shown in Table 3. (See Table 3.)

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Overall survival and complete remission rates in pre-specified disease-related sub-groups (i.e., cytogenetic risk, Eastern Cooperative Oncology Group [ECOG] score, age, type of AML, and baseline bone marrow blast count) were consistent with results for the overall study population.
The use of DACOGEN as initial therapy was also evaluated in an open-label, single-arm, Phase 2 study (DACO-017) in 55 subjects >60 years with AML according to the WHO classification. The primary endpoint was CR rate assessed by independent expert review. The secondary endpoint of the study was overall survival. DACOGEN was administered as a 1-hour intravenous infusion of 20 mg/m2 once daily for 5 consecutive days repeated every 4 weeks. In the ITT analysis, a CR rate of 23.6% (95% CI: 13.2% to 37%) was observed in 13/55 subjects treated with DACOGEN. The median time to CR was 4.1 months, and the median duration of CR was 18.2 months. The median overall survival in the intent-to-treat population was 7.6 months (95% CI: 5.7, 11.5).
Pharmacokinetics: The population pharmacokinetic (PK) parameters of decitabine were pooled from 3 clinical studies [DACO-017 (n=11), DACO-020 (n=11) and DACO-016 (n=23)] utilizing the 5-Day regimen (20 mg/m2 x 1-hour x 5 days every 4 weeks) and 1 study, DACO-018 (n=12), utilizing the 3-Day regimen (15 mg/m2 x 3-hours every 8 hours x 3 days every 6 weeks) in MDS or AML patients. In the 5-Day regimen, decitabine PK was evaluated on the fifth day of the first treatment cycle. Total dose per cycle was 100 mg/m2. In the 3-Day regimen, decitabine PK was evaluated after the first dose of each dosing day of the first treatment cycle. Total dose per cycle was 135 mg/m2.
Distribution: The pharmacokinetics of decitabine following intravenous administration as a 1-hour (5-Day regimen) or 3-hour (3-Day regimen) infusion was described by a linear two-compartment model, characterized by rapid elimination of the drug from the central compartment and by relatively slow distribution from the peripheral compartment. For a typical patient (weight 70 kg/body surface area 1.73 m2) the decitabine PK parameters are listed in Table 4 as follows. (See Table 4.)

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Decitabine exhibits linear PK and following the intravenous infusion, steady-state concentrations are reached within 0.5 hour. Based on model simulation, PK parameters were independent of time (i.e., did not change from cycle to cycle) and no accumulation was observed with this dosing regimen. Plasma protein binding of decitabine is negligible (<1%). Decitabine Vdss in cancer patients is large indicating distribution of the drug into peripheral tissues. There was no evidence of dependencies on age, creatinine clearance, total bilirubin, or disease.
Metabolism: Intracellularly, decitabine is activated through sequential phosphorylation via phosphokinase activities to the corresponding triphosphate, which is then incorporated by the DNA polymerase. In light of in vitro metabolism data, the human mass balance study results indicated that the cytochrome P450 system is not involved in the metabolism of decitabine. The primary route of metabolism is likely through deamination by cytidine deaminase in the liver, kidney, intestinal epithelium, and blood. Results from the human mass-balance study showed that unchanged decitabine in plasma accounted for approximately 2.4% of total radioactivity in plasma. The major circulating metabolites are not believed to be pharmacologically active. The presence of these metabolites in urine together with the high total body clearance and low urinary excretion of unchanged drug in the urine (~4% of the dose) indicate that decitabine is appreciably metabolized in vivo. In addition, in vitro data show that decitabine is a poor P-gp substrate.
Elimination: Mean plasma clearance following intravenous administration in cancer subjects was >200 L/h with moderate inter-subject variability (Coefficient of Variation [CV] is approximately 50%). Excretion of unchanged drug appears to play only a minor role in the elimination of decitabine.
Results from a mass balance study with radioactive 14C-decitabine in cancer patients showed that 90% of the administered dose of decitabine (4% unchanged drug) is excreted in the urine.
Special Populations: The effects of renal or hepatic impairment, gender, age or race on the pharmacokinetics of decitabine have not been formally studied. Information on special populations was derived from pharmacokinetic data from the 4 studies noted previously.
Elderly: Population pharmacokinetic analysis showed that decitabine PK are not dependent on age (range studied 40 to 87 years; median 70 years).
Hepatic impairment: The PK of decitabine have not been formally studied in patients with hepatic impairment. Results from a human mass-balance study and in vitro experiments mentioned previously indicated that the CYP enzymes are unlikely to be involved in the metabolism of decitabine. In addition, the limited data from the population PK analysis indicated no significant PK parameter dependencies on total bilirubin concentration despite a wide range of total bilirubin levels. Thus, decitabine exposure is not likely to be affected in patients with impaired hepatic function.
Renal impairment: The PK of decitabine have not been formally studied in patients with renal insufficiency. The population PK analysis on the limited decitabine data indicated no significant PK parameter dependencies on normalized creatinine clearance, an indicator of renal function. Thus, decitabine exposure is not likely to be affected in patients with impaired renal function.
Other Populations: Gender: Population PK analysis of decitabine did not show any clinically relevant different between men and women.
Race: Most of the patients studied were Caucasian. However, the population PK analysis of decitabine indicated that race had no apparent effect on the exposure to decitabine.
Toxicology: Non-Clinical Information: Formal carcinogenicity studies have not been performed with decitabine. Evidence from the literature indicates that decitabine has carcinogenic potential. The available data from in vitro and in vivo studies provide sufficient evidence that decitabine has genotoxic potential. Data from the literature also indicate that decitabine has adverse effects on all aspects of the reproductive cycle, including fertility, embryo-fetal development and post-natal development. Multi-cycle repeat-dose toxicity studies in rats and rabbits indicated that the primary toxicity was myelosuppression, including effects on bone marrow, which was reversible on cessation of treatment. Gastrointestinal toxicity was also observed and in males, testicular atrophy which did not reverse over the scheduled recovery periods. Decitabine administration to neonatal/juvenile rats showed a comparable general toxicity profile as in older rats. Neurobehavioral development and reproductive capacity were unaffected when neonatal/juvenile rats were treated at dose levels inducing myelosuppression.
Indications/Uses
DACOGEN is indicated for treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British (FAB) subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and Intermediate-1, Intermediate-2, and High-Risk International Prognostic Scoring System (IPSS) groups.
For the treatment of adult patients aged 65 and above with newly diagnosed de novo or secondary acute myeloid leukemia (AML), according to the World Health Organization (WHO) classification, who are not candidates for standard induction chemotherapy.
Dosage/Direction for Use
Treatment Regimen in Myelodysplastic Syndromes (MDS): There are two regimens for DACOGEN administration. With either regimen, it is recommended that patients be treated for a minimum of 4 cycles; however, a complete or partial response may take longer than 4 cycles.
Complete blood counts and platelet counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each cycle. Liver chemistries and serum creatinine should be obtained prior to initiation of treatment.
Treatment Regimen - Option 1: DACOGEN is administered at a dose of 15 mg/m2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days. This cycle should be repeated every 6 weeks. Patients may be premedicated with standard anti-emetic therapy.
If hematologic recovery (ANC ≥ 1,000/μL and platelets ≥ 50,000/μL) from a previous DACOGEN treatment cycle requires more than 6 weeks, then the next cycle of DACOGEN therapy should be delayed and dosing temporarily reduced by following this algorithm: Recovery requiring more than 6, but less than 8 weeks - DACOGEN dosing to be delayed for up to 2 weeks and the dose temporarily reduced to 11 mg/m2 every 8 hours (33 mg/m2/day, 99 mg/m2/cycle) upon restarting therapy.
Recovery requiring more than 8, but less than 10 weeks - Patient should be assessed for disease progression (by bone marrow aspirates); in the absence of progression, the DACOGEN dose should be delayed up to 2 more weeks and the dose reduced to 11 mg/m2 every 8 hours (33 mg/m2/day, 99 mg/m2/cycle) upon restarting therapy, then maintained or increased in subsequent cycles as clinically indicated.
Treatment Regimen - Option 2: DACOGEN is administered at a dose of 20 mg/m2 by continuous intravenous infusion over 1 hour repeated daily for 5 days. This cycle should be repeated every 4 weeks. Patients may be premedicated with standard anti-emetic therapy.
If myelosuppression is present, subsequent treatment cycles of DACOGEN should be delayed until there is hematologic recovery (ANC ≥ 1,000/μL platelets ≥ 50,000/μL ).
Patients with Non-hematologic Toxicity: Following the first cycle of DACOGEN treatment, if any of the following non-hematologic toxicities are present, DACOGEN treatment should not be restarted until the toxicity is resolved: serum creatinine ≥ 2 mg/dL; SGPT, total bilirubin ≥ 2 times ULN; and active or uncontrolled infection.
Treatment Regimen in Acute Myeloid Leukemia: In a treatment cycle, DACOGEN is administered at a dose of 20 mg/m2 body surface area by intravenous infusion over 1 hour repeated daily for 5 consecutive days (i.e., a total of 5 doses per treatment cycle). The total daily dose must not exceed 20 mg/m2 and the total dose per treatment cycle must not exceed 100 mg/m2. If a dose is missed, treatment should be resumed as soon as possible. The cycle should be repeated every 4 weeks depending on the patient's clinical response and observed toxicity. It is recommended that patients be treated for a minimum of 4 cycles; however, a complete or partial remission may take longer than 4 cycles to be obtained. Treatment may be continued as long as the patient shows response, continues to benefit or exhibits stable disease, i.e., in the absence of overt progression.
If after 4 cycles, the patient's hematological values (e.g., platelet count or absolute neutrophil count), have not returned to pre-treatment levels or if disease progression occurs (peripheral blast counts are increasing or bone marrow blast counts are worsening), the patient may be considered to be a non-responder and alternative therapeutic options to DACOGEN should be considered.
Pre-medication for the prevention of nausea and vomiting is not routinely recommended but may be administered if required.
Management of Myelosuppression and Associated Complications In AML: Myelosuppression and adverse events related to myelosuppression (thrombocytopenia, anemia, neutropenia, and febrile neutropenia) are common in both treated and untreated patients with AML. Complications of myelosuppression include infections and bleeding. Treatment may be delayed at the discretion of the treating physician, if the patient experiences myelosuppression-associated complications, such as those described as follows: Febrile neutropenia (temperature ≥ 38.5ºC and absolute neutrophil count < 1,000/μL).
Active viral, bacterial or fungal infection (i.e., requiring intravenous anti-infectives or extensive supportive care).
Hemorrhage (gastrointestinal, genito-urinary, pulmonary with platelets < 25,000/μL or any central nervous system hemorrhage).
Treatment with DACOGEN may be resumed once these conditions have improved or have been stabilized with adequate treatment (anti-infective therapy, transfusions, or growth factors).
In clinical studies, approximately one-third of patients receiving DACOGEN required a dose-delay. Dose reduction is not recommended.
Special Populations: Pediatrics: The safety and effectiveness in pediatric patients have not been established.
Hepatic impairment: Studies in patients with hepatic impairment have not been conducted. The need for dosage adjustment in patients with hepatic impairment has not been evaluated. If worsening hepatic function occurs, patients should be carefully monitored (see Precautions, Pharmacology: Pharmacokinetics under Actions).
Renal impairment: Studies in patients with renal impairment have not been conducted; however, data from clinical trials that included patients with mild-moderate impairment indicated no need for dosage adjustment. Patients with severe renal impairment were excluded from these trials (see Pharmacology: Pharmacokinetics under Actions).
Administration: DACOGEN is administered by intravenous infusion. A central venous catheter is not required. For instructions on reconstitution and dilution of the medicinal product before administration, see Instructions for Use and Handling and Disposal under Cautions for Usage.
Overdosage
There is no direct experience of human overdose and no specific antidote. However, early clinical study data in published literature at doses greater than 20 times higher than the current therapeutic doses, reported increased myelosuppression including prolonged neutropenia and thrombocytopenia. Toxicity is likely to manifest as exacerbations of adverse reactions, primarily myelosuppression (see Adverse Reactions). Treatment for overdose should be supportive.
Contraindications
Known hypersensitivity to decitabine or any of the excipients (see Excipients/Inactive Ingredients under Description).
Lactation (see Pregnancy, Breast-feeding and Fertility under Use in Pregnancy & Lactation).
Special Precautions
Myelosuppression: Myelosuppression and complications of myelosuppression, including infections and bleeding that occur in patients with MDS or AML may be exacerbated with DACOGEN treatment. Myelosuppression caused by DACOGEN is reversible. Complete blood and platelet counts should be performed regularly, as clinically indicated and prior to each treatment cycle. In the presence of myelosuppression or its complications, treatment with DACOGEN may be interrupted, the dose reduced or supportive measures instituted as recommended in Dosage & Administration, Adverse Reactions.
Hepatic Impairment: The use of DACOGEN in patients with hepatic impairment has not been established. Caution should be exercised in the administration of DACOGEN to patients with hepatic impairment or in patients who develop signs or symptoms of hepatic impairment. Patients should be monitored closely (see Dosage and Administration, Pharmacology: Pharmacokinetics under Actions).
Renal Impairment: The use of DACOGEN in patients with severe renal impairment has not been studied. Caution should be exercised in the administration of DACOGEN to patients with severe renal impairment (Creatinine Clearance [CrCl] <30 mL/min) and these patients should be monitored closely (see Dosage & Administration).
Cardiac Disease: Patients with a history of severe congestive heart failure or clinically unstable cardiac disease were excluded from clinical studies and therefore the safety and efficacy of DACOGEN in these patients has not been established.
Effects on Ability to Drive and Use Machines: No studies of the effects on the ability to drive or use machines with DACOGEN have been performed. Patients should be advised that they may experience undesirable effects, such as anemia, during treatment. Therefore, caution should be recommended when driving a car or operating machines.
Use In Pregnancy & Lactation
Pregnancy: Women of childbearing potential should be advised to use effective contraceptive measures and avoid becoming pregnant while being treated with DACOGEN. The time period following treatment with DACOGEN where it is safe to become pregnant is unknown. There are no adequate data on the use of DACOGEN in pregnant women. Studies have shown that decitabine is teratogenic in rats and mice (See Pharmacology: Toxicology: Non-clinical Information under Actions). The potential risk for humans is unknown. Based on results from animal studies and its mechanism of action, DACOGEN should not be used during pregnancy, unless clearly necessary. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving DACOGEN, the patient should be apprised of the potential hazard to the fetus.
Use in Males: Men should be advised to not father a child while receiving DACOGEN, and for 3 months following completion of treatment (see Pharmacology: Toxicology: Non-clinical Information under Actions).
Fertility: Female patients of childbearing potential should be advised to seek consultation regarding oocyte cryopreservation prior to initiation of treatment with DACOGEN. Because of the possibility of infertility as a consequence of DACOGEN therapy, men should be advised to seek advice on conservation of sperm prior to any treatment.
Breast-feeding: It is not known whether decitabine or its metabolites are excreted in breast milk. DACOGEN is contraindicated during lactation; therefore if treatment with DACOGEN is required, breast-feeding must be discontinued (see Contraindications).
Adverse Reactions
Clinical Study Data: Throughout this section, adverse reactions are presented. Adverse reactions are adverse events that were considered to be reasonably associated with the use of DACOGEN based on the comprehensive assessment of the available adverse event information. A causal relationship with DACOGEN cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The most important and frequently occurring adverse reactions in both the 5-Day and 3-Day regimens are myelosuppression and those occurring as a consequence of myelosuppression.
Adverse Reactions: The safety of DACOGEN was evaluated in 682 subjects from AML and MDS clinical studies (D-0007, DACO-016, DACO-017, DACO-020, EORTC-06011 and ID03-0180). In these clinical studies, DACOGEN was administered with the 5-Day or 3-Day dosing regimen. Adverse reactions reported during these clinical studies are summarized as follows in Table 5. The adverse reactions are listed by frequency category. Frequency categories are defined as follows: Very common (≥1/10), Common (≥1/100 to <1/10) and Uncommon (≥1/1,000 to <1/100).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 5.)

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Description of selected adverse reactions: Hematologic adverse reactions: The most commonly reported hematologic adverse reactions associated with DACOGEN treatment included febrile neutropenia, thrombocytopenia, neutropenia, anemia and leucopenia.
Serious infection-related adverse reactions such as septic shock, sepsis, and pneumonia were reported in patients receiving DACOGEN.
Serious bleeding-related adverse reactions such as CNS hemorrhage (1%) and gastrointestinal hemorrhage (2%), in the context of severe thrombocytopenia, were reported in patients receiving DACOGEN.
Hematological adverse reactions should be managed by routine monitoring of complete blood counts and supportive treatments as required. Supportive treatments include, administration of prophylactic antibiotics and/or growth factor support (e.g. G-CSF) for neutropenia and transfusions for anaemia or thrombocytopenia according to institutional guidelines. For situations where decitabine administration should be delayed, see Dosage & Administration.
Postmarketing Data: In addition to the adverse reactions reported during clinical studies and listed previously, the following adverse reactions have been reported during postmarketing experience. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In the table, the frequencies are provided according to the following convention: Very common ≥ 1/10, Common ≥ 1/100 and < 1/10, Uncommon ≥ 1/ 1000 and < 1/100, Rare ≥ 1/10000 and < 1/1000, Very rare < 1/10000, including isolated reports. (See Table 6.)

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Drug Interactions
No formal clinical drug interaction studies with decitabine have been conducted.
There is the potential for a drug-drug interaction with other agents which are also activated by sequential phosphorylation (via intracellular phosphokinase activities) and/or metabolized by enzymes implicated in the inactivation of decitabine (e.g., cytidine deaminase). Therefore, caution should be exercised if these drugs are combined with DACOGEN.
Impact of Co-administered Drugs on Decitabine: CYP450-mediated metabolic drug interactions are not anticipated as decitabine metabolism is not mediated by this system but by oxidative deamination. Displacement of decitabine from its plasma protein binding by co-administered drugs is unlikely given the negligible in vitro plasma protein binding (<1%) of decitabine. In vitro data indicated that decitabine is a poor P-glycoprotein (P-gp) substrate and is therefore not prone to interaction with P-gp inhibitors.
Impact of Decitabine on Co-administered Drugs: Given its low in vitro plasma protein binding (<1%), decitabine is unlikely to displace co-administered drugs from their plasma protein binding. In vitro studies show that decitabine does not inhibit nor induce CYP 450 enzymes up to more than 20-fold of the therapeutic maximum observed plasma concentration (Cmax). Thus, CYP-mediated metabolic drug interactions are not anticipated and is unlikely to interact with agents metabolized through these pathways. Decitabine has been shown to be a weak inhibitor of P-gp mediated transport in vitro and is therefore also not expected to affect P-gp mediated transport of co-administered drugs (See Pharmacology: Pharmacokinetics under Actions).
Caution For Usage
Instructions for Use and Handling and Disposal: This medicinal product is for single use only. Skin contact with the solution should be avoided and protective gloves must be worn. Standard procedures for dealing with anticancer agents should be adopted. DACOGEN should be aseptically reconstituted with 10 mL of Sterile Water for Injection. Upon reconstitution, each mL contains approximately 5.0 mg of decitabine at pH 6.7 to 7.3. Immediately after reconstitution, the solution should be further diluted with 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a final drug concentration of 0.15 to 1.0 mg/mL. Unless used within 15 minutes of reconstitution, the diluted solution must be prepared using cold (2°C to 8°C) infusion fluids and stored at 2°C to 8°C for up to a maximum of 4 hours until administration. Any unused product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. DACOGEN should not be infused through the same intravenous access/line with other medicinal products.
Storage
Unopened vial: Do not store above 25°C. For storage conditions of the reconstituted medical products see Instructions for Use, Handling and Disposal under Cautions for Usage.
Shelf-Life: 36 months.
Unopened vial: 3 years. Do not store above 25°C. After reconstitution: Unless used within 15 minutes of reconstitution, the diluted solution must be prepared using cold (2°C to 8°C) infusion fluids and stored at 2°C to 8°C for up to a maximum of 4 hours until administration.
ATC Classification
L01BC08 - decitabine ; Belongs to the class of antimetabolites, pyrimidine analogues. Used in the treatment of cancer.
Presentation/Packing
Powd for inj 50 mg (white to almost white sterile lyophilized powder in a vial) x 1's.
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