Dacogen decitabine dose, indications, adverse effects. Daunorubicin hydrochloride injection must be given into a rapidly flowing intravenous infusion. Decitabine is also being studied in the treatment of other conditions and types of cancer. In preclinical studies in mice and rats, decitabine was teratogenic, fetotoxic, and embryotoxic. In the fda approved prescribing information of dacogen for. Dacogen decitabine for injection product package insert.
Symptomatic patients often receive either azacitidine or decitabine, but which of these agents is the better choice. Decitabine definition of decitabine by medical dictionary. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions. Low doses of decitabine incorporated into dna lead to trapping and depletion of the. It hypomethylates dna by inhibiting dna methyltransferase it functions in a similar manner to azacitidine, although decitabine can only be incorporated into dna strands while azacitidine can be incorporated into both dna and rna chains it incorporates into dna strands upon replication, and then when dna methyltransferases dnmts such as dnmt1, are. Action inhibits dna methyltransferase, causing apoptosis. Decitabine has shown activity in some hematologic disorders including myelodysplastic syndromes mds, acute myelogenous. Highlights of prescribing information these highlights do. There are no adequate and wellcontrolled studies of dacogen in pregnant women. Decitabine is the deoxyderivative of azacitidine and hence is an analog of deoxycytidine. Unless used within 15 minutes of reconstitution, the diluted. Along with its needed effects, decitabine may cause some unwanted effects.
Therapeutic effects improved hematologic and clinical. Decitabineinduced changes in human myelodysplastic syndrome. Severe local tissue necrosis will occur if there is extravasation during administration. Our dacogen decitabine for injection side effects drug center provides a comprehensive view of available drug information on the potential side effects when taking this. Supplemental tables and figures pdf, 873 kb pdf file. Based on its mechanism of action, decitabine alters dna synthesis and is expected to result in adverse reproductive effects see clinical pharmacology 12. The calculated dose of the resulting solution is drawn into a syringe and administered only intravenously.
We investigated the effects of dac treatment on the myeloid mds cell line skm1. Dacogen decitabine for injection description e 59 66. Each singleuse vial of dacogen 50 mg contains decitabine as. Addition of lowdose decitabine to antipd1 antibody. Treatment of newly diagnosed acute myeloid leukaemia in patients over 65 years of age who are not candidates for standard induction chemotherapy. Decitabine is available as a singleuse 50mg lyophilized powder vial from multiple manufacturers. A retrospective pooled analysis of 2 decitabine clinical trials in patients with mds conducted cox regression analyses of red blood cell or platelet dependence, myelosuppression, dose modification, cycle delay or dose reduction, and survival effects. A favorable inductive remission rate for decitabine combined with. It must neverbe given by the intramuscular or subcutaneous route. Dacogen decitabine forinjection, for intravenous use initial u. Plerixafor can be safely added to decitabine in poorprognosis, elderly acute.
Breastfeeding while receiving dacogen is not recommended. Highlights of prescribing information these highlights do not. A healthcare provider will give you this injection. D indications treatment of various myelodysplastic syndromes mds. Dacogen has been approved in the 2006 for the treatment of usa since odysplastic may myel syndrome. Dailymed dacarbazine injection, powder, for solution. A small proportion of orally administered drug undergoes bacterial degradation with each cycle of enterohepatic circulation. Dacogen decitabine for injection description dacogen decitabine for injection contains decitabine 5aza2deoxycytidine, an analogue of the natural nucleoside 2deoxycytidine.
Complete blood counts and platelet counts should be performed as needed to monitor response. Beyond conjugation, ursodiol is not altered or catabolized appreciably by the liver or intestinal mucosa. Discard any unused portion of the reconstituted solution. Aug 11, 2017 the management of patients with low or intermediaterisk myelodysplastic syndrome mds includes supportive care, azacitidine, decitabine, lenalidomide, and immunosuppressive agents such as antithymocyte globulin and cyclosporine. Recommended vial diluent, dilution solutions, and storage following reconstitution and dilution differ among products. Dacogen was studied in 3 singlearm studies n 66, n 98, n 99 and 1 controlled supportive care study n 83 dacogen, n 81 supportive care. Word will convert the pdf to editable text and you can then copy and paste that text into your office document. The reconstituted solution may be further diluted with 5% dextrose injection or sodium chloride injection and administered as an intravenous infusion. Decitabine trade name dacogen, or 5aza2deoxycytidine, acts as an nucleic acid synthesis inhibitor. Pdf myelodysplastic syndromes mds are clonal bone marrow malignancies characterized by. Decitabine was approved by the us food and drug admin. Pdf decitabine in the treatment of myelodysplastic syndromesj.
The developmental toxicity of 99 decitabine was examined in mice exposed to single ip intraperitoneal injections 0, 0. Decitabine is an antineoplastic cancer medicine this medicine is available only with your doctors prescription. Dacogen decitabine for injection contains decitabine 5aza2deoxycitidine, an analogue of the natural nucleoside 2deoxycytidine. Side effects requiring immediate medical attention. This 3day treatment is usually repeated every 6 weeks at least 4 times. Discussion of clinically important adverse reactions. Tracking decitabine incorporation into malignant myeloid cell dna. Stability indicating rphplc method for the estimation of. As in any fire, wear selfcontained breathing apparatus pressuredemand niosh approved or. Oct 18, 2019 azacitidine or decitabine can also be dose reduced. Fasligand, and propidium iodide pi were purchased from sigmaaldrich, rpmi. Once diluted into an intravenous bag or bottle as described above, dalvance may be stored either refrigerated at 2 to 8 c 36 to 46 f or at a controlled room temperature of 20 to 25 c 68 to 77 f. Side effects of dacogen decitabine injection, warnings, uses. We present a case of cardiomyopathy associated with decitabine used.
In most cases, a decitabine injection is given every 8 hours for 3 days. Decitabine is a fine, white to almost white powder with the molecular formula of c 8 h 12 n 4 o 4 and a molecular weight of 228. Based on its mechanism of action, dacogen is expected to result in adverse reproductive effects. The median duration of treatment for patients on decitabine arm was 4. Decitabine injection is used to treat myelodysplastic syndromes, a group of cancers in which immature blood cells in the bone marrow do not mature and do not become healthy blood cells. Decitabine induced delayed cardiomyopathy in hematologic. Pdf an update on the safety and efficacy of decitabine in the. Immediately after reconstitution, the solution should be further diluted with 0. Dacogen decitabine for injection description e 59 66 57 70. Decitabine fda prescribing information, side effects and uses. Actigall ursodiol, usp capsules rx only special note.
Dacogen decitabine chemotherapy, side effects navigating care. Decitabine fda prescribing information, side effects and. Adverse drug reactions reported in 293 aml patients treated with dacogen are summarised in. No information is available on the pharmacokinetics of decitabine at the indicated dosage of 15 mgm. Methylation inhibitor therapy in the treattment of myelodysplastic syndrome. Patients treated with decitabine received a 1hour infusion, once daily for 5 consecutive days every 4 weeks. Decitabine inhibits dnmt1 after incorporating into dna during s phase. Decitabine can cause fetal harm when administered to a pregnant woman. Grade 12 adverse events observed in over 20% of subjects, regardless of drug attribution. Decitabine is a cytosine nucleoside analogue which inhibits dna methyltransferase and is intended for the treatment of acute myeloid leukaemia aml. Decitabine side effects, dosage, interactions drugs. This medicine is available only with your doctors prescription. In the trial, patients received 15 mgm 2 intravenously every 8 hours for 3 days every 6 weeks. For more information, go to edit pdf content in word.
The cell cycle stages of the skm1 cells were assessed using a pi staining. As decitabine is known to boost tcell function, we assessed the safety and efficacy of antipd1 camrelizumab alone versus decitabineprimed. Decitabine is a prodrug that has to be converted into a nucleoside triphosphate to become an active drug. Intravenous iv decitabine and oral bexarotene for acute. Intravenous iv decitabine and oral bexarotene for acute myelogenous leukemia aml aml the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. The following data is based on the product molecular weight 228. Although its mechanism of action is similar to azacitidine, the key difference lies in azacitidines ability to incorporate into rna, while decitabine does not 53.
Aug, 2019 commonly reported side effects of decitabine include. Nov 01, 2014 the calculated dose of the resulting solution is drawn into a syringe and administered only intravenously. Myelosuppression in myelodysplastic syndromes mds is associated with the hypomethylating agent decitabine. Decitabine in the treatment of myelodysplastic syndromes.
In the controlled trial using decitabine dosed at 15 mgm2, administered by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days, the highest incidence of grade 3 or grade 4 adverse events in the decitabine arm were neutropenia 87%, thrombocytopenia 85%, febrile neutropenia 23% and leukopenia 22%. It is a drug for the treatment of myelodysplastic syndromes, a class of conditions where certain blood cells are dysfunctional, and for acute myeloid leukemia aml. The data described below reflect exposure to dacogen in 83 patients in the mds trial. Medlineplus information on decitabine a lay language summary. Decitabine comes as a powder to be to be added to fluid and injected slowly over 3 hours intravenously into a vein by a doctor or nurse in a medical office or hospital outpatient clinic. Decitabine in the treatment of myelodysplastic syndromesj.
Physicochemical stability of reconstituted decitabine dacogen. Targets dna methyltransferase hl60 dna methyltransferase kg1a ic50 100 ngml 1 ngml 1 in vitro decitabine inhibits cell growth in a dose and timedependent manner with ic50 of approximately 438. Some clinicians prefer decitabine because it is given intravenously over acute myeloid leukemia. Nov 09, 2018 decitabine is injected into a vein through an iv. See below for a comprehensive list of adverse effects. Study of pdr001 andor mbg453 in combination with decitabine. Mar 01, 2020 decitabine for injection contains decitabine 5aza2deoxycitidine, an analogue of the natural nucleoside 2deoxycytidine. Methylation is a process in which methyl ch3 groups are added to dna. In vitro studies demonstrated dosage and timedependent incorporation of decitabine into myeloid leukemia cell dna that correlated with.
As a consequence, tumor suppressor genes aberrantly silenced after methylation can be reactivated and expressed. Although its mechanism of action is similar to azacitidine, the key difference lies in azacitidines ability to incorporate into. Dacogen can cause fetal harm when administered to a pregnant woman. Decitabine supplier cas 2353335 2deoxy5azacytidine. Easy to read fda package insert, drug facts, dosage and administration, and adverse effects for buspar buspirone. Azacitidine or decitabine can also be dose reduced. Mar 06, 2020 dacogen decitabine for injection contains decitabine 5aza2deoxycitidine, an analogue of the natural nucleoside 2deoxycytidine.
In a treatment cycle, dacogen is administered at a dose of 20 mgm2 bodysurface area by. Mar 06, 2020 it is unknown if this drug passes into breast milk or if it could harm a nursing baby. Dacogen decitabine showed an overall survival advantage. Decitabine incorporates into dna and inhibits dna methyltransferase, resulting in hypomethylation of dna and intrasphase arrest of dna replication. Decitabine was administered as an intravenous infusion of 20 mgm2 over 1 hour h on.
Simply put, a high enough dose of the drug is required for intracellular. Decitabine dosing for mds is 15 mgm 2 via a 3hour continu ous infusion three times a day for 3 days for the. Decitabine is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into dna and inhibition of dna methyltransferase, causing hypomethylation of dna and cellular differentiation or apoptosis. The sites of the drugs therapeutic actions are in the liver, bile, and gut lumen.
Patients treated with cytarabine received 20 mgm 2 subcutaneously once daily 10 consecutive days every 4 weeks. About dacogen decitabine for injection dacogen is a hypomethylating agent that is believed to exert its antineoplastic effects by incorporation into dna and inhibition of an enzyme called dna methyltransferase. Decitabine dosing for mds is 15 mgm 2 via a 3hour continuous. In particular, the combinations including dac did not add extra. Feb 06, 2020 decitabine is given as an infusion into a vein. Definition from the nci drug dictionary detailed scientific definition and other names for this drug. This treatment period is called a cycle, and the cycle may be repeated every 6 weeks for as long as your. Listing a study does not mean it has been evaluated by the u. If youre looking to insert the contents of your pdf file into an office file, as opposed to simply inserting the pdf as an attachment, then your best bet is to open that pdf with word 20 or 2016. Phase i trial of plerixafor combined with decitabine in newly.
The mechanism of action of decitabine is as a nucleic acid. Pdf decitabine in the treatment of acute myeloid leukemia. Nonproliferating cells are relatively insensitive to decitabine. Decitabine is a fine, white to almost white powder with the. Decitabine is a potent inhibitor of dna methylation with ic50 of 438 nm and 4.
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