Enoxaparin: OD vs BD dosing regimen in Cancer Patients

• Two enoxaparin dosing schemes are FDA-approved for the treatment of DVT with or without PE in hospitalizedpatients:
• enoxaparin 1 mg/kg SC every 12 hours
• enoxaparin 1.5 mg/kg SC every 24 hours

Rationale in Cancer Patient

• Currently, no study has directly compared enoxaparin 1.5 mg/kg SC once daily versus 1 mg/kg SC twice daily as the primary outcome for the long-term treatment of VTE in cancer patients
• Based on the results of the Merli trial, the ONCENOX trial, and the CANTHANOX trial which showed higher rates of major bleeding from using 1.5 mg/kg SC once daily versus 1 mg/kg SC twice daily, we recommend that in patients at a higher risk of bleeding that 1 mg/kg SC twice daily dosing of enoxaparin be used. 
• (patients at a higher risk of bleeding, thrombocytopenia, brain metastases, young female during menstruation with or without thrombocytopenia)
• We hypothesize that the seemingly higher bleeding rate may be due to achieving higher peak plasma anti-Xa concentrations.
• One meta-analysis evaluated 1522 cancer and non-cancer patients from five studies who received either once- or twice-daily LMWH and concluded that once daily dosing appears to be as safe and effective as twice daily dosing; however, the possibility of a higher frequency of fatal bleeding with once daily therapy could not be excluded
• several patient-specific factors that may be used to help balance efficacy, bleeding risk, cost, and convenience for cancer patients being treated with enoxaparin for VTE
• Factors which indicate higher-risk for both recurrent VTE and bleeding among cancer patients and which may suggest an advantage for twice daily enoxaparin therapy include prior VTE, certain concomitant medications (hormonal or chemotherapy), chemotherapy-induced thrombocytopenia, poor performance status, obesity, large ileofemoral DVT, and massive PE
• In addition, patients with brain tumors or metastases have a particularly higher risk of hemorrhage with anticoagulation therapy, which carries up to a 45% incidence of mortality in the event of a bleed.
• Therefore, we recommend enoxaparin 1 mg/kg SC twice daily dosing for these high-risk patients in order to minimize risk of intracranial hemorrhage
• In contrast, patients without these high-risk factors or patients with renal dysfunction in whom higher
• total-dose LMWH (twice daily enoxaparin) may increase bleeding risk may benefit from once-daily dosing
• patients with severe renal dysfunction (creatinine clearance <30 mL/min) require lower doses such as enoxaparin 1 mg/kg SC once daily.

Recommendation