Therapy | Hydroxyurea (1998) (Siklos, Hydrea) | L-glutamine (2017) (Endari) | Voxelotor (2019, 2021) (Oxbryta) | Crizanlizumab (2019) (Adakveo) |
Age | All ages including infants | 5 years and older* | 4 years and older* | 16 years and older* |
Route | Oral (pill or liquid; liquid used for young children requires formulary preparation) | Oral (powder added to food or beverages) | Oral (tablet) | Intravenous |
Frequency | Once daily | Twice daily | Once daily | Once every 4 weeks (after initial dose week 0, 2, and 4) |
Monitoring | Frequent monitoring of CBC and dose titration, especially during drug initiation | None | None | None |
Benefits | - Improved life expectancy
- Reduced acute pain episodes (4.5 versus 2.5)¶
- Reduced vaso-occlusive complications including acute chest syndrome and stroke (selected individuals)
- Reduced transfusion requirement
- 25 years of safety and efficacy data
| - Reduced acute pain episodes (4 versus 3)¶
- Can be combined with hydroxyurea
- Good safety profile
| - Non-statistically significant trend towards reduced acute pain episodes (3.2 versus 2.8)¶
- Can be combined with hydroxyurea
- Increased hemoglobin and decreased hemolysis
- Improved global functioning
- May improve fatigue
| - Reduced in acute pain episodes (3 versus 1.6)¶
- Can be combined with hydroxyurea
- Good choice for severe and frequent pain episodes
|
Caveats | - Hair loss
- Gastrointestinal symptoms
- Generally avoid prior to conception (males and females) and during first trimester of pregnancy
| - Use pharmacologic grade (not over-the-counter) L-glutamine
- Mild gastrointestinal symptoms
- Long-term efficacy data are lacking
| - Dose adjustments for CYP3A4 interactions
- Gastrointestinal symptoms
- Monitor hemoglobin in individuals with higher baseline hemoglobin (eg, HbSC disease)
| - Requires intravenous access and hospital infusions
- Infusion reactions (rare)
- Arthralgias and back pain
- Nausea
- May cause platelet clumping in samples collected in EDTA
|