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Indications and Dosage
Parenteral
Myelodysplastic disease Adult: Initially, 75 mg/m2 daily via SC inj or IV infusion over 10-40 min for 7 days, followed by a rest period of 21 days (28-day cycle), may be increased to 100 mg/m2 daily if there is no benefit after 2 cycles, and no toxicity other than nausea and vomiting has occurred. Recommended treatment duration: Min of 4 to 6 cycles; continued as long as the patient benefits, or until disease progression. Dose adjustment may be needed for haematological toxicity.
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Renal Impairment
Reduce dose by 50% on the next cycle if serum bicarbonate falls to <20 mmol/L. Delay next treatment cycle if serum creatinine or BUN is >2 times the baseline value and above the upper limit of normal (ULN) until values return to normal or baseline, and then reduce dose by 50% on the next cycle.
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Reconstitution
IV: Add 10 mL of sterile water for inj to a vial containing 100 mg to obtain a final concentration of 10 mg/mL. Shake vigorously until soln is dissolved and clear. Further dilute reconstituted soln w/ 50-100 mL of NaCl 0.9% or lactated Ringer's inj for IV infusion. SC: Slowly add 4 mL of sterile water for inj to a vial containing 100 mg to obtain a final concentration of 25 mg/mL. Shake vigorously until a susp is formed (susp will be cloudy).
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Incompatibility
Incompatible w/ dextrose 5% soln, hetastarch, glucose- or bicarbonate-containing soln.
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Contraindications
Advanced malignant hepatic tumour. Pregnancy and lactation.
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Special Precautions
Patient w/ high tumour burden, history of severe CHF, clinically unstable cardiac disease or pulmonary disease. Renal and severe hepatic impairment.
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Adverse Reactions
Significant: Nausea and vomiting, anaemia, neutropenia, thrombocytopenia, GI or intracranial haemorrhage, hepatotoxicity, renal tubular acidosis, elevated serum creatinine, inj site reactions (e.g. erythema, pain).
Nervous: Insomnia, headache, fatigue, dizziness, anxiety. GI: Abdominal pain, anorexia, constipation, diarrhoea, dyspepsia, mucositis. Resp: Dyspnoea. Hepatic: Elevated LFT. Endocrine: Hypokalaemia. Haematologic: Bruising, petechiae. Dermatologic: Rash, itch, alopecia. Immunologic: Infection, hypersensitivity reactions. Others: Fever. Potentially Fatal: Progressive hepatic coma, renal failure, tumour lysis syndrome, necrotising fasciitis. |
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IV/Parenteral/SC: D
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Patient Counseling Information
This drug may cause fatigue, if affected, do not drive or operate machinery.
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Monitoring Parameters
Monitor LFT, CBC, electrolytes, serum creatinine and bicarbonate at baseline and before each treatment cycle, and as clinically indicated. Monitor for bleeding, nausea and vomiting, and inj site reactions. Consider cardiopulmonary assessment prior to and during treatment.
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Overdosage
Symptoms: Nausea, vomiting, diarrhoea. Management: Supportive treatment.
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Action
Description:
Mechanism of Action: Azacitidine, a synthetic pyrimidine nucleoside analog of cytidine, is believed to exert its antineoplastic effects by inhibiting DNA methyltransferase (the enzyme responsible for methylating newly synthesised DNA in mammalian cells) thereby causing hypomethylation of DNA and by direct toxicity on abnormal hematopoietic cells in the bone marrow. Pharmacokinetics: Absorption: Rapidly and completely absorbed (SC). Bioavailability: Approx 89% (SC). Time to peak plasma concentration: 30 min (SC). Distribution: Volume of distribution: 76 ± 26 L (IV). Metabolism: Metabolised in the liver via spontaneous hydrolysis and deamination by cytidine deaminase into several metabolites. Excretion: Mainly via urine, approx 50% (SC) and 85% (IV), as metabolites; faeces (<1%). Elimination half-life: Approx 4 hr. |
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Chemical Structure
 Source: National Center for Biotechnology Information. PubChem Database. Azacitidine, CID=9444, https://pubchem.ncbi.nlm.nih.gov/compound/Azacitidine (accessed on Jan. 21, 2020) |
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Storage
Store at 25°C.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, admin, and disposal. |
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MIMS Class
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ATC Classification
L01BC07 - azacitidine ; Belongs to the class of antimetabolites, pyrimidine analogues. Used in the treatment of cancer.
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References
Anon. Azacitidine . Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 14/06/2017. Azacitidine for Injection, Powder, Lyophilized, for Solution (Seton Pharmaceuticals). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 14/06/2017. Buckingham R (ed). Azacitidine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 14/06/2017. Joint Formulary Committee. Azacitidine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 14/06/2017. McEvoy GK, Snow EK, Miller J et al (eds). Azacitidine . AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 14/06/2017.
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