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DEMYLOCAN is a brand name for Decitabine, supplied as a powder. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: DemylocanTM is indicated for the treatment of adult patients with: Myelodysplastic Syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts,…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations Patients may be premedicated with standard anti-emetic therapy. See WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests. 2 Recommended Dose and Dosage Adjustment There are two regimens for DemylocanTM administration.
For either regimen, it is recommended that patients be treated for a minimum of 4 cycles unless unacceptable toxicities occur after dose delays/adjustments or standard supportive care. A complete or partial response may take longer than 4 cycles.
Treatment should be continued as long as the patient continues to benefit or until disease progression. Treatment Regimen – Option 1 DemylocanTM 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. If hematologic recovery (ANC ≥ 1,000/mcL and platelets ≥ 50,000/mcL) from a previous DemylocanTM treatment cycle requires more than 6 weeks, then the next cycle of therapy should be delayed and dosing temporarily reduced by following this algorithm: Recovery requiring more than 6, but less than 8 weeks − DemylocanTM 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 DemylocanTM 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.
DemylocanTM Product Monograph PENDOPHARM, Division of Pharmascience Inc. Page 6 of 38 Treatment Regimen – Option 2 DemylocanTM 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. If myelosuppression is present, subsequent treatment cycles of DemylocanTM should be delayed until there is hematologic recovery (ANC ≥ 1,000/mcL platelets ≥ 50,000/mcL). Dose Adjustment Non-hematologic Toxicity (Both Treatment Regimens) Following the first cycle of DemylocanTM treatment, if any of the following non-hematologic toxicities are present, treatment should not be restarted until the toxicity is resolved: 1) serum creatinine ≥ 2 mg/dL; 2) SGPT, total bilirubin ≥ 2 times ULN; 3) and active or uncontrolled infection.
1 Adverse Reaction Overview The decitabine safety database is comprised of available data from nine primary studies in 704 patients with MDS who received at least one dose of decitabine. In Study D-0007, the controlled study under the inpatient dosing regimen, AEs were reported by almost all patients (98%-100%).
The most common AEs (> 30%) were neutropenia, thrombocytopenia, anemia, fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, and hyperglycemia. In general, the incidence of most AEs decreased after the first 3 cycles.
Neutropenia, thrombocytopenia and anemia, however, continued to be common during the first 6 cycles. At least one SAE was reported in 69% and 56% of patients in the decitabine arm and supportive care (SC) arm, respectively. The highest incidence of Grade 3 or 4 adverse events in the decitabine arm were neutropenia (87%), thrombocytopenia (85%), febrile neutropenia (23%) and leukopenia (22%).
The SAE with the greatest difference between treatment arms was febrile neutropenia, 25% versus 5%, decitabine versus SC, respectively. More patients in the decitabine arm versus the SC arm (34% versus 21%) reported infections associated with SAEs; these ranged from pneumonia (17% versus 12%, decitabine versus SC, respectively) and catheter related infections (5% versus 0%), to a wide variety of bacterial and fungal infections reported in 1 or 2 patients each.
Bone marrow suppression was the most frequent cause of dose reduction, delay, and discontinuation. Six patients had fatal events associated with their underlying disease and myelosuppression that were considered at least possibly related to drug treatment.
Eight decitabine-treated patients permanently discontinued therapy for AEs, compared to 1 patient in the SC arm. Decitabine dose was temporarily decreased or delayed in 35%. Adverse events most frequently (≥ 1%) resulting in clinical intervention in the decitabine arm were as follows: DemylocanTM Product Monograph PENDOPHARM, Division of Pharmascience Inc.
Please see the Serious Warnings and Precautions Box at the beginning of Part 1:
Health Professional Information. Carcinogenesis and Mutagenesis Based on non-clinical findings, decitabine has carcinogenic and mutagenic potential (see NON- CLINICAL TOXICOLOGY). Cardiovascular 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 DemylocanTM in these patients has not been established.
Driving and Operating Machinery DemylocanTM may have a moderate influence on the ability to drive and use machines. Patients may experience fatigue, dizziness, confusional state, and blurred vision during treatment. Due caution should be exercised when driving or operating a vehicle or potentially dangerous machinery.
Hematologic Treatment with decitabine is associated with neutropenia and thrombocytopenia, including an increase in frequency and severity of these events compared to baseline (see ADVERSE Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Intravenous Lyophilized powder / 50 mg decitabine Potassium Dihydrogen Phosphate; Sodium Hydroxide DemylocanTM Product Monograph PENDOPHARM, Division of Pharmascience Inc.
Page 9 of 38 REACTIONS). In clinical trials, myelosuppression was the most frequent cause of dose adjustment and study drug discontinuation. Complete blood and platelet counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle (see Monitoring and Laboratory Tests).
After administration of the recommended dosage for the first cycle, treatment for subsequent cycles may require dose adjustment (see DOSAGE AND ADMINISTRATION). Complications of myelosuppression include infections and bleeding. Serious infection-related adverse events, such as pneumonia and sepsis, and serious bleeding-related adverse events, such as intracranial hemorrhage, some with fatal outcomes, have been reported in patients receiving decitabine in clinical trials (see ADVERSE REACTIONS).
Patients who are hypersensitive to DemylocanTM or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
Breastfeeding women (see WARNINGS AND PRECAUTIONS, Special Populations).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Other brands of Decitabine in Canada.
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Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Renal Impairment Decitabine has not been studied in patients with renal impairment and the need for dose adjustment in those patients is unknown. Patients with renal impairment should be closely monitored for toxicity including worsening renal function since decitabine and its metabolites are primarily excreted through the kidney (see WARNINGS AND PRECAUTIONS).
Hepatic Impairment Decitabine has not been studied in patients with hepatic impairment and the need for dose adjustment in those patients is unknown. Patients with hepatic impairment should be closely monitored for toxicities including worsening liver functions (see WARNINGS AND PRECAUTIONS).
3 Administration Treatment Regimen – Option 1 Administer DemylocanTM intravenously as a 3-hour infusion and repeat every 8 hours for 3 days. Repeat this cycle every 6 weeks. Treatment Regimen – Option 2 Administer DemylocanTM intravenously at a dose of 20 mg/m2 over 1 hour repeated daily for 5 days.
Repeat this cycle every 4 weeks. DemylocanTM Product Monograph PENDOPHARM, Division of Pharmascience Inc. 4 Reconstitution DemylocanTM is a cytotoxic drug and caution should be exercised when handling and preparing. See SPECIAL HANDLING.
3. 1 -1 mg/mL. Unless used within 15 minutes of reconstitution, the diluted solution must be prepared using cold (2 to 8°C) infusion fluids and stored at 2 to 8°C for up to a maximum of 4 hours until administration (see STORAGE, STABILITY and DISPOSAL).
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if there is evidence of particulate matter or discoloration.
Page 12 of 38 Discontinuation: thrombocytopenia, neutropenia, pneumonia, Mycobacterium avium complex infection, cardio-respiratory arrest, increased blood bilirubin, intracranial hemorrhage, abnormal liver function tests. Dose Delayed: neutropenia, pulmonary edema, atrial fibrillation, central line infection, febrile neutropenia.
Dose Reduced: neutropenia, thrombocytopenia, anemia, lethargy, edema, tachycardia, depression, pharyngitis. In the Alternative Dosing for Outpatient Treatment (ADOPT) Trial, the single arm study conducted in North America under the outpatient dosing regimen, the most common AEs (> 30%) were fatigue, nausea, neutropenia, pyrexia, and anemia.
The highest incidence of Grade 3 or 4 AEs were neutropenia (37%), thrombocytopenia (24%), and anemia (22%). The most common infections associated with SAEs were pneumonia, sepsis, and septic shock. Seventy-eight percent of patients had dose delays, the median duration of this delay was 7 days and the largest percentage of delays was due to hematologic toxicities.
Hematologic toxicities and infections were the most frequent causes of dose delays and discontinuation. Eight patients had fatal events due to infection and/or bleeding (seven of which occurred in the clinical setting of myelosuppression) that were considered at least possibly related to drug treatment.
Nineteen of 99 patients permanently discontinued therapy for adverse events. 2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
Study D-0007:
Controlled Clinical Trial in Patients with MDS - Inpatient Dosing Regimen The data described below reflect exposure to decitabine in 83 patients in Study D-0007 under the inpatient dosing regimen. Patients received 15 mg/m2 intravenously over 3 hours every 8 hours for 3 consecutive days every 6 weeks (1 cycle).
The median number of decitabine cycles was 3 (range 0 to 9). Patients with a history of severe congestive heart failure or clinically unstable cardiac disease, renal dysfunction, or hepatic dysfunction were excluded. DemylocanTM Product Monograph PENDOPHARM, Division of Pharmascience Inc.
Page 13 of 38 Table 3:
Adverse Events Reported in ≥ 5% of Patients in the Decitabine Group and at a Rate Greater than Supportive Care in Study D-0007 Decitabine N = 83 (%) Supportive Care N = 81 (%) Blood and lymphatic system disorders Neutropenia 75 (90) 58 (72) Thrombocytopenia 74 (89) 64 (79) Anemia NOS 68 (82) 60 (74) Febrile neutropenia 24 (29) 5 (6) Leukopenia NOS 23 (28) 11 (14) Lymphadenopathy 10 (12) 6 (7) Thrombocythemia 4 (5) 1 (1) Cardiac disorders Pulmonary edema NOS 5 (6) 0 (0) Eye disorders Vision blurred 5 (6) 0 (0) Gastrointestinal disorders Nausea 35 (42) 13 (16) Constipation 29 (35) 11 (14) Diarrhea NOS 28 (34) 13 (16) Vomiting NOS 21 (25) 7 (9) Abdominal pain NOS 12 (14) 5 (6) Oral mucosal petechiae 11 (13) 4 (5) Stomatitis 10 (12) 5 (6) Dyspepsia 10 (12) 1 (1) Ascites 8 (10) 2 (2) Gingival bleeding 7 (8) 5 (6) Hemorrhoids 7 (8) 3 (4) Loose stools 6 (7) 3 (4) Tongue ulceration 6 (7) 2 (2) Dysphagia 5 (6) 2 (2) Oral soft tissue disorder NOS 5 (6) 1 (1) Lip ulceration 4 (5) 3 (4) Abdominal distension 4 (5) 1 (1) Abdominal pain upper 4 (5) 1 (1) Gastro-esophageal reflux disease 4 (5) 0 (0) Glossodynia 4 (5) 0 (0) General disorders and administrative site disorders Pyrexia 44 (53) 23 (28) Edema peripheral 21 (25) 13 (16) Rigors 18 (22) 14 (17) Edema NOS 15 (18) 5 (6) Pain NOS 11 (13) 5 (6) Lethargy 10 (12) 3 (4) Tenderness NOS 9 (11) 0 (0) Fall 7 (8) 3 (4) Chest discomfort 6 (7) 3 (4) DemylocanTM Product Monograph PENDOPHARM, Division of Pharmascience Inc.
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Careful clinical surveillance for myelosuppression-related complications is recommended. Healthcare professionals should consider the need for early institution of growth factors and/or antimicrobial agents for the prevention or treatment of infections.
Blood product support, per institutional guidelines, may be required for thrombocytopenia and anemia. Patients should be advised to monitor and report any symptoms of neutropenia, thrombocytopenia, or fever to their healthcare professional as soon as possible.
Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles, and may not necessarily indicate progression of underlying MDS. Monitoring and Laboratory Tests Complete blood 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 (see Special Populations). Sexual Health Reproduction Women of childbearing potential should be advised to avoid becoming pregnant while receiving DemylocanTM.
The time period following treatment with DemylocanTM where it is safe to become pregnant is unknown. Women of childbearing potential should be counseled to use effective contraception during this time (see SPECIAL POPULATIONS). Men should be advised not to father a child while receiving treatment with DemylocanTM, and for 3 months following completion of treatment (see NON-CLINICAL TOXICOLOGY).
Men with female partners of childbearing potential should use effective contraception during this time. The use of decitabine with hormonal contraceptives has not been studied. DemylocanTM Product Monograph PENDOPHARM, Division of Pharmascience Inc.
Page 10 of 38 Fertility No human data on the effect of decitabine on fertility are available. In non-clinical animal studies, decitabine alters male fertility and is mutagenic. Because of the possibility of infertility as a consequence of DemylocanTM therapy, men should seek advice on conservation of sperm and female patients of childbearing potential should seek consultation regarding oocyte cryopreservation prior to initiation of treatment (see NON-CLINICAL TOXICOLOGY).
1 Pregnant Women There are no adequate data on the use of decitabine in pregnant women. Decitabine has been shown to cause teratogenicity and embryo-fetal toxicity when administered to pregnant rodents, in the absence of maternal toxicity (see NON-CLINICAL TOXICOLOGY).
Decitabine is expected to result in adverse reproductive effects when administered to a pregnant woman. DemylocanTM should not be used during pregnancy and in women of childbearing potential not using effective contraception. If DemylocanTM is used during pregnancy, or if a patient becomes pregnant while receiving DemylocanTM, the patient should be apprised of the potential hazard to the fetus.
2 Breastfeeding It is unknown if decitabine or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants who are exposed to decitabine, DemylocanTM is contraindicated during breastfeeding (see NON-CLINICAL TOXICOLOGY).
If treatment with DemylocanTM is required, breastfeeding must be discontinued. 3 Pediatrics Pediatrics (< 18 years of age): The safety of DemylocanTM in pediatric patients has not been established. Animal data in juvenile rodents have shown toxicity (see NON-CLINICAL TOXICOLOGY).
4 Geriatrics Geriatrics (≥ 65 years of age): Of the total number of patients exposed to decitabine in the controlled clinical trial under the inpatient dosing regimen, 61 of 83 patients were age 65 and over, while 21 of 83 patients were age 75 and over.
Of the total number of patients exposed to decitabine in the single-arm trial under the […]