Azacitidine - Vidaza®
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|NS, LR [Note: INCOMPATIBLE with dextrose]|
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|Instructions for Subcutaneous Administration|
|Stability / Miscellaneous|
Mechanism of Action
Published studies indicate that urinary excretion is the primary route of elimination of azacitidine and its metabolites. Following IV administration of radioactive azacitidine to 5 cancer patients, the cumulative urinary excretion was 85% of the radioactive dose. Fecal excretion accounted for <1% of administered radioactivity over 3 days. Mean excretion of radioactivity in urine following SC administration of 14C-azacitidine was 50%. The mean elimination half-lives of total radioactivity (azacitidine and its metabolites) were similar after IV and SC administrations, about 4 hours.
An in vitro study of azacitidine incubation in human liver fractions indicated that azacitidine may be metabolized by the liver. Whether azacitidine metabolism may be affected by known microsomal enzyme inhibitors or inducers has not been studied.
The potential of azacitidine to inhibit cytochrome P450 (CYP) enzymes is not known.
In vitro studies with human cultured hepatocytes indicate that azacitidine at concentrations of 1.0 µM to 100 µM does not induce CYP 1A2, 2C19, or 3A4/5.
1. INDICATIONS AND USAGE
1.1 Myelodysplastic Syndromes (MDS)
2.1 First Treatment Cycle
2.2 Subsequent Treatment Cycles
Patients should be monitored for hematologic response and renal toxicities [see Warnings and Precautions (5.3) PACKAGE INSERT ], and dosage delay or reduction as described below may be necessary.
2.3 Dosage Adjustment Based on Hematology Laboratory Values
For patients with baseline (start of treatment) WBC ≥3.0 x109/L, ANC ≥1.5 x109/L, and platelets ≥75.0 x109/L, adjust the dose as follows, based on nadir counts for any given cycle:
For patients whose baseline counts are WBC <3.0 x109/L, ANC<1.5 x109/L, or platelets <75.0 x109/L, dose adjustments should be based on nadir counts and bone marrow biopsy cellularity at the time of the nadir as noted below, unless there is clear improvement in differentiation (percentage of mature granulocytes is higher and ANC is higher than at onset of that course) at the time of the next cycle, in which case the dose of the current treatment should be continued.
If a nadir as defined in the table above has occurred, the next course of treatment should be given 28 days after the start of the preceding course, provided that both the WBC and the platelet counts are >25% above the nadir and rising. If a >25% increase above the nadir is not seen by day 28, counts should be reassessed every 7 days. If a 25% increase is not seen by day 42, then the patient should be treated with 50% of the scheduled dose.
2.4 Dosage Adjustment Based on Renal Function and Serum Electrolytes
2.5 Use in Geriatric Patients
2.6 Preparation of VIDAZA
If reconstituted VIDAZA comes into contact with the skin, immediately and thoroughly wash with soap and water. If it comes into contact with mucous membranes, flush thoroughly with water.
The VIDAZA vial is single-use and does not contain any preservatives. Unused portions of each vial should be discarded properly [see How Supplied/Storage and Handling]. Do not save any unused portions for later administration.
2.7 Instructions for Subcutaneous Administration
Preparation for Immediate Subcutaneous Administration: Doses greater than 4 mL should be divided equally into 2 syringes. The product may be held at room temperature for up to 1 hour, but must be administered within 1 hour after reconstitution.
Preparation for Delayed Subcutaneous Administration: The reconstituted product may be kept in the vial or drawn into a syringe. Doses greater than 4 mL should be divided equally into 2 syringes. The product must be refrigerated immediately, and may be held under refrigerated conditions (2ºC - 8ºC, 36ºF - 46ºF) for up to 8 hours. After removal from refrigerated conditions, the suspension may be allowed to equilibrate to room temperature for up to 30 minutes prior to administration.
VIDAZA suspension is administered subcutaneously. Doses greater than 4 mL should be divided equally into 2 syringes and injected into 2 separate sites. Rotate sites for each injection (thigh, abdomen, or upper arm). New injections should be given at least one inch from an old site and never into areas where the site is tender, bruised, red, or hard.
Suspension Stability: VIDAZA reconstituted for subcutaneous administration may be stored for up to 1 hour at 25°C (77°F) or for up to 8 hours between 2°C and 8°C (36°F and 46°F).
2.8 Instructions for Intravenous Administration
Withdraw the required amount of VIDAZA solution to deliver the desired dose and inject into a 50 -100 mL infusion bag of either 0.9% Sodium Chloride Injection or Lactated Ringer's Injection.
Intravenous Solution Incompatibility
Solution Stability: VIDAZA reconstituted for intravenous administration may be stored at 25°C (77°F), but administration must be completed within 1 hour of reconstitution.
3. DOSAGE FORMS AND STRENGTHS
4.1 Advanced Malignant Hepatic Tumors
4.2 Hypersensitivity to Azacitidine or Mannitol
HOW SUPPLIED/STORAGE AND HANDLING
Handling and Disposal
[PACKAGE INSERT DATA] : Celgene Corporation. Summit, NJ 07901. VIDAZA (azacitidine) injection Package insert. 09/2008.
1] Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings. NIOSH Alert 2004-165.
2] OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. https://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html
3] American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. (2006) 63:1172-1193.
4] Polovich, M., White, J. M., & Kelleher, L.O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd. ed.) Pittsburgh, PA: Oncology Nursing Society.
Azacitidine – Vidaza®