DESCRIPTION
Azacitidine
MECHANISM OF ACTION
• Cytidine analog.
• Cell cycle–specific with activity in the S-phase.
• Requires activation to the nucleotide metabolite azacitidine triphosphate.
• Incorporation of azacitidine triphosphate into RNA, resulting in inhibition of RNA processing and function.
• Incorporation of azacitidine triphosphate into DNA, resulting in inhibition of DNA methyltransferases, which then leads to loss of DNA methylation and gene reactivation. Aberrantly silenced genes, such as tumor
suppressor genes, are reactivated and expressed.
ABSORPTION
Not available for oral use and is administered via the SC and IV route. The bioavailability of SC azacitidine is 89% relative to IV azacitidine.
DISTRIBUTION
Distribution in humans has not been fully characterized. The drug is able to cross the blood-brain barrier.
INDICATIONS
FDA-approved for treatment of patients with myelodysplastic syndromes (MDS), including refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
DOSAGE RANGE
Recommended dose is 75 mg/m2 SC or IV daily for 7 days. Cycles should be repeated every 4 weeks.
DRUG INTERACTIONS
None characterized to date.
SPECIAL CONSIDERATIONS
1. Patients should be treated for a minimum of 4 cycles, as it may take longer than 4 cycles for clinical benefit.
2. Patients should be pretreated with effective antiemetics to prevent nausea/vomiting.
3. Monitor complete blood counts on a regular basis during therapy.
4. Use with caution in patients with underlying kidney dysfunction. If unexplained elevations in BUN or serum creatinine occur, the next cycle should be delayed, and the subsequent dose should be reduced by 50%. If unexplained reductions in serum bicarbonate levels to < 20 mEq/L occur, the subsequent dose should be reduced by 50%.
5. Pregnancy category D. Breastfeeding should be avoided.
TOXICITY 1
Myelosuppression with neutropenia and thrombocytopenia.
TOXICITY 2
Fatigue and anorexia.
TOXICITY 3
GI toxicity in the form of nausea/vomiting, constipation, and abdominal pain.
TOXICITY 4
Renal toxicity with elevations in serum creatinine, renal tubular acidosis, and hypokalemia.
TOXICITY 5
Peripheral edema.
SPECIFICATION
Login To Comment