Azacitidine

SCOPE: the published dose is the parenteral (subcutaneous/intravenous) MDS regimen, which is this page's primary route and regimen (the page's own route field and its 'typical: 75 mg/m2 days 1-7 every 28-day cycle' text). The oral regimen is a different product, route, indication and dose and is quoted in full below but is NOT published in the dose field. VERBATIM (US injection label §2.2, First Treatment Cycle for Adults): 'The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m 2 subcutaneously or intravenously, daily for 7 days. Premedicate patients for nausea and vomiting. Obtain complete blood counts, liver chemistries and serum creatinine prior to the first dose.' VERBATIM (§2.3, Subsequent Treatment Cycles for Adults): 'Repeat cycles every 4 weeks. The dose may be increased to 100 mg/m 2 if no beneficial effect is seen after 2 treatment cycles and if no toxicity other than nausea and vomiting has occurred. It is recommended that patients be treated for a minimum of 4 to 6 cycles. However, complete or partial response may require additional treatment cycles. Treatment may be continued as long as the patient continues to benefit.' MAXDOSE LEFT EMPTY: no figure anywhere in either fetched label is labelled a maximum dose; the highest parenteral figure is the escalation to 100 mg/m2, which is a per-body-surface-area escalation and not a stated ceiling. DOSE ADJUSTMENT BY NADIR COUNTS (§2.5): for adults with baseline WBC >=3x10^9/L, ANC >=1.5x10^9/L and platelets >=75x10^9/L, the percentage dose in the next course is 50% for a nadir ANC <0.5x10^9/L or platelets <25x10^9/L, 67% for ANC 0.5-1.5 or platelets 25-50x10^9/L, and 100% for ANC >1.5 and platelets >50x10^9/L; for patients with lower baseline counts the next-course percentage (100/50/33%) is read off a table of percentage decrease from baseline against bone marrow biopsy cellularity at nadir. 'If a nadir as defined in the table above has occurred, give the next course 28 days after the start of the preceding course, provided that both the WBC and the platelet counts are greater than 25% above the nadir and rising. If a greater than 25% increase above the nadir is not seen by day 28, reassess counts every 7 days. If a 25% increase is not seen by day 42, reduce the scheduled dose by 50%.' SUBCUTANEOUS ADMINISTRATION (§2.9, verbatim): 'Reconstitute Azacitidine for injection aseptically with 4 mL Sterile Water for Injection, USP to obtain a concentration of 25 mg/mL... For doses requiring more than 1 vial, divide the dose equally between the syringes (e.g., dose 150 mg = 6 mL, 2 syringes with 3 mL in each syringe) and inject into two separate sites.' Azacitidine for injection is a hazardous drug; vials are single-dose and preservative-free — discard unused portions. ORAL ROUTE, NOT PUBLISHED ABOVE (UK SPC §4.2 for Azacitidine 200 mg film-coated tablets, verbatim): 'The recommended dose is 300 mg azacitidine orally once daily. Each repeated cycle consists of a treatment period of 14 days followed by a treatment free period of 14 days (28-day treatment cycle). Azacitidine treatment should be continued until no more than 15% blasts are observed in peripheral blood or bone marrow or until unacceptable toxicity.' Patients are to be treated with an anti-emetic 30 minutes prior to each dose for the first 2 treatment cycles. On AML relapse with 5% to 15% blasts an extension of the dosing schedule from 14 to 21 days of repeated 28-day cycles should be considered, and 'Dosing should not exceed 21 days during any 28-day period'; azacitidine should be discontinued if more than 15% blasts are seen. The oral toxicity dose reduction step is to 200 mg, then a 7-day reduction in treatment duration, then discontinuation. Tablets 'should be swallowed whole with a glass of water at about the same time each day. They should not be split, crushed, dissolved or chewed', with or without food. NON-INTERCHANGEABILITY (both labels): US §2.1 'Do not substitute Azacitidine for injection for oral azacitidine. The indications and dosing regimen for Azacitidine for injection differ from that of oral azacitidine'; US §5.1 'Treatment of patients using Azacitidine for Injection at the recommended dosage of oral azacitidine may result in a fatal adverse reaction.'; UK SPC 'Azacitidine should not be used interchangeably with injectable azacitidine due to differences in the exposure, dose and schedule of treatment. Healthcare professionals are recommended to verify the name of the medicinal product, dose and administration route.' ELDERLY: UK SPC 'No dose adjustments are recommended for patients over 65 years of age'; US §2.7/§8.5 advise careful dose selection and renal monitoring because elderly patients are more likely to have decreased renal function. SPECIALIST USE: 'Azacitidine treatment should be initiated and monitored under the supervision of a physician experienced in the use of chemotherapeutic medicinal products' (UK SPC §4.2). TRUNCATION: the US §2.9 text ends at the source-fetch limit, so any regimen beyond that point was not retrieved.