Common Side Effects of Azacitidine
Azacitidine commonly causes hematologic toxicities (cytopenias), gastrointestinal disturbances, and injection site reactions, with most side effects being manageable with supportive care and dose adjustments when necessary. 1
Hematologic Toxicities
Hematologic toxicities are the most common and significant side effects of azacitidine:
- Neutropenia: Can lead to increased risk of infections
- Thrombocytopenia: May cause bleeding complications
- Anemia: Results in fatigue and reduced quality of life
These cytopenias typically occur during early treatment cycles and tend to decrease in frequency during subsequent cycles 2. Management includes:
- Dose delays (required in 23-29% of patients)
- Growth factor support
- Blood transfusions as needed
Gastrointestinal Side Effects
Common gastrointestinal adverse events include:
- Nausea (occurring in up to 70% of patients)
- Vomiting
- Diarrhea
- Constipation
These can be managed with:
- Anti-emetics for nausea/vomiting
- Laxatives for constipation
- Appropriate hydration
Administration-Related Reactions
- Injection site reactions: Erythema, pain, bruising (more common with subcutaneous administration)
- These reactions tend to be more pronounced during the first 1-2 treatment cycles 1
Other Common Side Effects
- Fatigue
- Pyrexia (reported in 49.3% of patients) 3
- Insomnia
- Anxiety
- Dizziness
- Petechiae
- Pruritus/rash
- Hypokalemia
Serious Adverse Events
Though less common, serious adverse events can occur:
- Infections: Pneumonia and sepsis (each reported in about 10% of patients) 3
- Febrile neutropenia: Higher risk when combined with other agents 3
- Pneumonitis: Rare but potentially serious adverse reaction (reported in <0.1% of cases) 4
- Tumor lysis syndrome: Particularly in early treatment phases 5
- Cardiac failure: Rare but associated with high mortality 5
Timing of Side Effects
Most adverse events occur within the first month of treatment, with 90% of hematologic responses seen by cycle 6 3. Side effects that tend to be more pronounced during the first 1-2 cycles include:
- Thrombocytopenia
- Neutropenia
- Anemia
- Nausea/vomiting
- Injection site reactions
- Constipation
- Petechiae
- Dizziness
- Anxiety
- Hypokalemia
- Insomnia 1
Management Considerations
- Hematologic monitoring: Regular complete blood counts, especially during early cycles
- Infection prevention: Consider prophylactic antibiotics and antifungals in high-risk patients 3
- Dose modifications: May be necessary based on blood counts and toxicity
- Administration technique: Proper subcutaneous injection technique can minimize injection site reactions
- Supportive care: Anti-emetics, growth factors, and transfusions as needed
Special Considerations
- Most adverse events (>83%) are transient and resolve during ongoing therapy 2
- Subcutaneous administration may have fewer systemic side effects compared to intravenous administration 5
- Elderly patients and those with renal impairment require closer monitoring 1
- Drug interactions: Azacitidine is metabolized by cytidine deaminase, not through CYP450 enzymes 1
The key to successful azacitidine therapy is aggressive prevention and management of side effects to maintain adequate dose intensity for treatment effectiveness 6.