Clofarabine

Dose-dependent, reversible myelosuppression (neutropenia, thrombocytopenia, and anemia) is common; may be severe and prolonged. Monitor blood counts and platelets. May be at increased risk for infection due to neutropenia. Monitor for signs and symptoms of infection and treat promptly if infection develops; may require discontinuation.

Cytokine release syndrome (eg, tachypnea, tachycardia, hypotension, pulmonary edema) may develop into capillary leak syndrome/SIRS, and organ dysfunction; immediately discontinue with signs/symptoms of SIRS or capillary leak syndrome (rapid-onset respiratory distress, hypotension, pleural/pericardial effusion, and multiorgan failure) and manage appropriately. Consider supportive treatment with diuretics, corticosteroids, and/or albumin. Prophylactic corticosteroids may prevent or diminish the signs/symptoms of cytokine release. May require dosage reduction.

Serious and fatal cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. Discontinue clofarabine for exfoliative or bullous rash, or if SJS or TEN are suspected.

Clofarabine is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016). Serious and fatal enterocolitis (including neutropenic colitis, cecitis, and C. difficile colitis) has been reported, usually occurring within 30 days of treatment, and when used in combination with other chemotherapy. May lead to necrosis, perforation, hemorrhage or sepsis complications. Monitor for signs/symptoms of enterocolitis and manage promptly.

Serious and fatal hemorrhages (including cerebral, gastrointestinal, and pulmonary hemorrhage) have occurred, usually associated with thrombocytopenia. Monitor and manage coagulation parameters.

Transaminases and bilirubin may be increased during treatment; hepatitis and hepatic failure have been reported. Transaminase elevations generally occur within 10 days of administration and persist for ≤15 days. In some cases, hepatotoxicity was severe and fatal. The risk for hepatotoxicity, including hepatic sinusoidal obstruction syndrome (SOS; formerly called veno-occlusive disease [VOD]), is increased in patients who have previously undergone a hematopoietic stem cell transplant; discontinue if SOS is suspected. Avoid the concomitant use of drugs that may cause hepatotoxicity. Monitor liver function closely; discontinue immediately for grade ≥ 3 elevations in hepatic enzymes and/or bilirubin.

Monitor blood pressure during 5 days of treatment; discontinue if hypotension develops. Monitor if on concurrent medications known to affect blood pressure.

The risk for infections, including opportunistic infection or sepsis (may be severe or fatal), is increased due to prolonged neutropenia and immunocompromised state. Monitor for signs and symptoms of infection and treat promptly if infection develops; may require therapy discontinuation.

Elevated creatinine, acute renal failure, and hematuria were observed in clinical studies. Infection, sepsis, or tumor lysis syndrome may cause an increased risk of renal toxicity in patients receiving clofarabine. Monitor renal function closely; may require dosage reduction or therapy discontinuation.

Tumor lysis syndrome may occur as a consequence of leukemia treatment, including treatment with clofarabine, usually occurring in the first treatment cycle. May lead to life-threatening acute renal failure; adequate hydration and prophylactic antihyperuricemic therapy throughout treatment will reduce the risk/effects of tumor lysis syndrome; monitor closely. Disease-related concerns:

A pharmacokinetic study demonstrated that systemic exposure increases as creatinine clearance decreases (CrCl Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.