Best Review For [500:<25,000 50% 500 1500 25,000 50,000 67%> 1500 >50,000 100% Dosage Modification for Hematologic Toxicity in Patients with Baseline (start of treatment) WBC of <3000/mm 3 , ANC of> <1500/mm 3 , or Platelet Count of> <75,000/mm 3 Sub-Q or IV Base dosage adjustments on nadir blood cell counts and bone marrow biopsy cellularity at the time of the nadir count (see Table 2), unless clear improvement in differentiation (increased percentage of mature granulocytes and higher ANC) is observed at the time of initiation of the subsequent cycle relative to the time of initiation of the previous cycle. 1 If such improvement in differentiation is observed, continue the current dosage. 1 The next 7-day course of azacitidine should be given 28 days after initiation of the previous course, provided that both the WBC and platelet counts at day 28 exceed the nadir counts by 25% and are increasing. 1 If an increase in WBC and platelet counts of 25% has not occurred by day 28, reassess these blood cell counts every 7 days; 1 if increases of 25% do not occur by day 42, patients should receive 50% of the scheduled dosage. 1 Table 2. Dosage Modification for Hematologic Toxicity if Baseline WBC is> <3000/mm3, ANC is> <1500/mm3, or Platelet Count is> <75,000/mm31 Nadir WBC or Platelet Count (expressed as % decrease from baseline count) Bone Marrow Biopsy Cellularity (%) at Time of Nadir Count Dosage in Next Cycle (expressed as % of dose in previous cycle) 50 75 30 60 100 15 30 50> <15 33> 75 30 60 75 15 30 50 <15 33 Dosage Modification for Renal Impairment Sub-Q or IV If unexplained elevations of BUN or S cr occur, delay the next cycle until such values return to normal or baseline levels and reduce the dosage of azacitidine in the next treatment cycle by 50%. 1 Dosage Modification for Serum Electrolyte Disturbances Sub-Q or IV If unexplained decreases in serum bicarbonate concentrations (to> <20 mEq/L) occur, reduce the dosage of azacitidine in the next treatment cycle by 50%. 1 Special Populations No special population dosage recommendations at this time. 1 9 Cautions for Azacitidine Contraindications Known hypersensitivity to azacitidine or mannitol. 1 Advanced malignant hepatic tumors. 1 Warnings/Precautions Hematologic Effects. Possible neutropenia, thrombocytopenia, or anemia. 1 Perform CBC and platelet counts prior to each treatment cycle and periodically thereafter as needed. 1 After administration of the recommended dosage for the first cycle, reduce or delay dosage for subsequent cycles based on nadir blood cell counts and hematologic response. 1 (See Dosage under Dosage and Administration.) Hepatotoxicity Progressive hepatic coma and death reported rarely in patients with extensive tumor burden secondary to metastatic disease, particularly in those with baseline serum albumin concentrations of> <3 g/dL. 1 Contraindicated in patients with advanced malignant hepatic tumors. 1 Perform liver function tests prior to initiation of therapy. 1 Renal Toxicity Renal abnormalities (e.g., elevated S cr , renal tubular acidosis), renal failure, and death reported rarely in patients treated with IV azacitidine in combination with other antineoplastic agents (e.g., etoposide) for conditions other than MDS (e.g., chronic myelogenous leukemia). 1 Determine S cr prior to initiation of therapy. 1 If unexplained reductions in serum bicarbonate concentrations to> <20 mEq/L or elevations of BUN or S cr occur, reduce the dosage or withhold therapy with the drug. 1 (See Dosage under Dosage and Administration.) Fetal/Neonatal Morbidity and Mortality May cause fetal harm; teratogenicity and embryolethality demonstrated in animals. 1 Avoid pregnancy during therapy. 1 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard. 1 Advise male patients to not father a child while receiving azacitidine. 1 Specific Populations Pregnancy Category D. 1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Lactation Not known whether azacitidine or its metabolites are distributed into milk. 1 Discontinue nursing or the drug. 1 Pediatric Use Safety and efficacy not established in children> <16 years of age. 13 Geriatric Use No substantial differences in safety and efficacy relative to younger adults. 1 Assess renal function periodically, since azacitidine and its metabolites are substantially eliminated by the kidneys and geriatric patients are more likely to have decreased renal function. 1 Hepatic Impairment Potentially hepatotoxic in patients with severe preexisting hepatic impairment; use with caution in patients with liver disease. 1 (See Hepatotoxicity under Cautions.) Safety and efficacy not established in patients with MDS and hepatic impairment. 1 Renal Impairment Close monitoring for toxicity is recommended. 1 Azacitidine and its metabolites are substantially eliminated by the kidneys. 1 Safety and efficacy not established in patients with MDS and renal impairment. 1 Common Adverse Effects Sub-Q or IV administration: Nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, fatigue, injection site erythema, constipation, neutropenia, ecchymosis. 1 With IV administration, petechiae, rigors, weakness, and hypokalemia also occur commonly. 1 Interactions for Azacitidine Not known whether metabolism of azacitidine is affected by known inhibitors or inducers of hepatic microsomal enzymes. 1 Not known whether azacitidine inhibits CYP isoenzymes. 1 Azacitidine does not induce CYP isoenzyme 1A2, 2C19, 3A4, or 3A5 in vitro. 1 No formal drug interaction studies to date. 1 Azacitidine Pharmacokinetics Absorption Bioavailability Rapidly absorbed after sub-Q administration, with peak plasma concentration attained in about 0.5 hour. 1 Bioavailability is 89% relative to an IV dose. 1 Elimination Metabolism In vitro study suggests that azacitidine may be metabolized in the liver. 1 Elimination Route Azacitidine and its metabolites are eliminated principally in urine. 1 Half-life Elimination half-life is about 4 hours. 1 Stability Storage Parenteral Powder for Injection Powder: 25 C (may be exposed to 15 30 C). 1 Reconstituted suspension for sub-Q injection (in vial or syringe): 25 C for up to 1 hour or 2 8 C for up to 8 hours. 1 Refrigerated suspensions may be allowed to equilibrate to room temperature for up to 30 minutes prior to administration. 1 Reconstituted solution for IV infusion: 25 C; complete IV administration within 1 hour of reconstitution. 1 Compatibility For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral Solution Compatibility 1 Compatible Ringer s injection, lactated Sodium chloride 0.9% Incompatible Dextrose in water Hetastarch Drug Compatibility Incompatible with solutions containing sodium bicarbonate. 1 Actions Exerts antineoplastic effect by inhibiting DNA methyltransferase, thereby causing hypomethylation of DNA, 6 7 and by direct cytotoxic effect on abnormal hematopoietic cells in the bone marrow. 1 9 Advice to Patients Importance of women informing clinicians immediately if they are or plan to become pregnant. 1 Advise women to avoid pregnancy and advise men not to father a child during therapy. 1 Importance of women informing clinicians if they plan to breast-feed. 1 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., underlying hepatic or renal disease). 1 Importance of informing patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. azaCITIDine Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral For injection, for IV or subcutaneous use 100 mg Vidaza Celgene AHFS DI Essentials. Copyright 2017, Selected Revisions May 23, 2011. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. Use is not currently included in the labeling approved by the US Food and Drug Administration. References 1. Celgene Corporation. Vidaza (azacitidine for injection) prescribing information. Summit, NJ; 2008 Aug. 2. Gryn J, Zeigler ZR, Shadduck RK et al. Treatment of myelodysplastic syndromes with 5-azacytidine. Leuk Res . 2002; 26:893-7. [PubMed 12163049] 3. Suwanawiboon B, Sumida KN. 5-Azacitidine: an alternative treatment of myelodysplastic syndromes in patients with refractory response to hematopoietic growth factor; a case report and review of literature. Hawaii Med J . 2004; 63:14-6, 25. [PubMed 15011897] 4. Leone G, Voso MT, Teofili L et al. Inhibitors of DNA methylation in the treatment of hematological malignancies and MDS. Clin Immunol . 2003; 109:89-102. [PubMed 14585280] 5. Food and Drug Administration. Orphan designation pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act. (P.L. 97-414). Rockville, MD; From FDA website. 6. Silverman LR, Demakos EP, Bercedis L et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol . 2002; 20:2429-40. [PubMed 12011120] 7. Silverman LR. Targeting hypomethylation of DNA to achieve cellular differentiation in myelodysplastic syndromes (MDS). Oncologist . 2001; 6(Suppl 5):8-14. [PubMed 11700387] 8. Kantarjian HM. Treatment of myelodysplastic syndrome: questions raised by the azacitidine experience. J Clin Oncol . 2002; 20:2415-6. [PubMed 12011118] 9. Pharmion. AHFS Product information form on Vidaza (azacitidine) for injectable suspension. Boulder, CO; undated. 10. Silverman LR, Holland JF, Davis RB et al. Azacitidine (Aza C) in myelodysplastic syndromes (MDS). Ann Hematol . 1994; 68:A12. 11. Silverman LR, Holland JF, Weinberg RS et al. Effect of treatment with 5-azacitidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes. Leukemia . 1993; 7(Suppl):21-9. [PubMed 7683352] 12. US Food and Drug Administration Center for Drug Evaluation and Research. Azacitidine medical officer s review. 2004 May 19. From FDA website. 13. Pharmion, Boulder, CO; Personal communication. 14. Pharmion. Vidaza (azacitidine for injectable suspension) prescribing information. Boulder, CO; 2004 Aug 31. 10001. Silverman L, McKenzie D, Peterson B et al. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol . 2006; 24: 3895-3903. [PubMed 16921040] 10002. Sudan N, Rossetti J, Shadduck R et al. Treatment of acute myelogenous leukemia with outpatient azacitidine. Cancer . 2006; 107:1839-43. [PubMed 16967444] 10003. Kaminskas E, Farrell A, Abraham S et al. Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res . 2005; 11: 3604-3608. [PubMed 15897554] 10004. Fenaux P, Mutfi G, Santini V et al. Azacitidine treatment prolongs overall survival in higher-risk MDS patients compared with conventional care regimens: Results of the AZA-001 Phase III study. Blood . 2007; 110: Abstract No. 817. 10005. List AF, Fenaux P, Mutfi GJ et al. Effect of azacitidine (AZA) on overall survival in higher-risk myelodysplastic syndromes (MDS) without complete remission. J Clin Oncol . 2008; 26: Abstract No. 7006. 10006. Mufti GJ, Fenaux P, Hellstrom-Lindberg E. et al. Treatment of high-risk MDS patients (pts) with -7/del(7q) with azacitidine (AZA) versus conventional care regimens (CCR): effects on overall survival. J Clin Oncol . 2008; 26: Abstract No. 7033. 10007. Fabre C, Gardin G, Mbida R et al. Treatment of AML with Azacytidine (AZA): Current results of the French ATU program. Blood . 2007; 110 (11): Abstract No. 1849. 10008. Al-Ali H, Schwind S, Becket C et al. 5-Azacitidine induces hematologic responses in a high proportion of patients with acute myeloid leukemia refractory to or not eligible for intensive chemotherapy. Blood . 2006; 108: Abstract No. 1953 10009. Goldberg S, Hsu J, Orr A et al. 5-Azacitidine therapy in elderly patients with acute myelogenous leukemia yields similar survival compared to 3+ 7 induction chemotherapy with less transfusional support, bacteremias and hospital days. Blood . 2006; 108: Abstract No. 4569. 10010. Jain N, Mattiuzzi G, Cortes J et al. Benefit of anti-infectious prophylaxis in patients with acute myeloid leukemia or high-risk myelodysplastic syndrome receiving frontline targeted therapy. Blood . 2007; 110: Abstract No. 2858. 10011. AHFS drug information off-label use determinations. McEvoy GK, ed. Azacitidine. Bethesda, MD: American Society of Health-System Pharmacists; 2008 Apr. From AHFS drug information website. 10012. Silverman LR, Demakos EP, Peterson BL et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol . 2002; 20:2429-40. [PubMed 12011120] 10013. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002; 100:2292-302. [PubMed 12239137] Next Interactions Print this page Add to My Med List More about azacitidine Side Effects During Pregnancy Dosage Information Drug Interactions Support Group Pricing & Coupons En Español 13 Reviews Add your own review/rating Drug class: miscellaneous antineoplastics Consumer resources Azacitidine Azacitidine Subcutaneous (Advanced Reading) Professional resources Azacitidine Injection (FDA) AzaCITIDine (Wolters Kluwer) Other brands: Vidaza Related treatment guides Myelodysplastic Syndrome> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only D Pregnancy Category Positive evidence of risk N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturers Dr. Reddy's Laboratories, Inc. Sandoz Inc. 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