Table 3.
Monitoring and management of hypertension, hepatotoxicity, neutropenia, and diarrhea associated with fostamatinib [8]
| How should BP be monitored and managed? | ||
| Monitoring | Assess at baseline; monitor every 2 weeks until a stable dosage is established, then monthly | |
| Stage 1 hypertension (SBP 130–139 or DBP 80–89 mmHg) | Initiate or ↑ dosage of antihypertensive in patients with ↑cardiovascular risk; adjust as needed until BP is controlled | |
| BP target is not met after 8 weeks: ↓ fostamatinib dosage | ||
| Stage 2 hypertension (SBP ≥ 140 or DBP ≥ 90 mmHg) | Initiate or ↑ dosage of antihypertensive; adjust as needed until BP is controlled | |
| BP remains ≥ 140/90 mmHg for > 8 weeks: ↓ fostamatinib dosage | ||
| BP remains ≥ 160/100 mmHg for > 4 weeks despite aggressive antihypertensive therapy: interrupt or discontinue fostamatinib | ||
| Hypertensive crisis (SBP > 180 and/or DBP > 120 mmHg) | ||
| How should hepatotoxicity be monitored and managed? | ||
| Monitoring | Perform LFTs, including ALT, AST and BL,at baseline, then monthly during treatment | |
| AST/ALT ≥ 3 × ULN and < 5 × ULN | Symptomatic patients (e.g. nausea, vomiting, abdominal pain): interrupt fostamatinib; check LFTs every 72 h until ALT/AST < 1.5 × ULN and total BL < 2 × ULN; resume fostamatinib at next lower daily dose | |
| Asymptomatic patients: check LFTs every 72 h until ALT/AST < 1.5 × ULN and total BL < 2 × ULN; consider dose interruption (or ↓) if ALT/AST remains 3–5 × ULN and total BL remains < 2 × ULN; resume fostamatinib at next lower daily dose when ALT/AST no longer ↑ (< 1.5 × ULN) and total BL remains < 2 × ULN | ||
| AST/ALT ≥ 5 × ULN and total BL < 2 × ULN | Interrupt fostamatinib; check LFTs every 72 h until AST/ALT no longer ↑ (< 1.5 × ULN) and total BL remains < 2 × ULN; resume fostamatinib at next lower daily dose | |
| Discontinue fostamatinib if AST/ALT remain ≥ 5 × ULN for ≥ 2 weeks | ||
| AST/ALT ≥ 3 × ULN and total BL > 2 × ULN | Discontinue fostamatinib | |
| ↑ Unconjugated (indirect) BL in absence of other LFT abnormalities | Continue fostamatinib with frequent monitoring (isolated ↑in unconjugated BL may be due to UGT1A1 inhibition) | |
| How should neutropenia be monitored and managed? | ||
| Monitoring | Perform complete blood counts, including neutrophils, at baseline, and regularly during treatment | |
| ANC < 1.0 × 109/L and remains low after 72 h | Interrupt fostamatinib | |
| ANC > 1.5 × 109/L | Resume fostamatinib at next lower daily dosage | |
| How should diarrhea be managed? | ||
| Onset of symptoms | Provide supportive measures (e.g. dietary changes, hydration and/or antidiarrheal medication) until symptoms resolve | |
| Severe (≥ grade 3) | Interrupt fostamatinib; resume treatment at next lower daily dosage if diarrhea improves to mild (grade 1) | |
ANC absolute neutrophil count, BP blood pressure, BL bilirubin, DBP diastolic BP, LFT liver function test, SBP systolic BP, UGT glucuronosyltransferase, ULN upper limit of normal, ↑ increase(d)/elevated, ↓ decrease