Infusion reactions occur more frequently on the first day of infusion and tend to decrease with subsequent infusions. Patients with a history of decreased pulmonary function may be at a greater risk for pulmonary complications from severe reactions and should be monitored closely during infusion of ofatumumab.

Tumour lysis syndrome

In patients with CLL, tumour lysis syndrome (TLS) may occur with use of ofatumumab. Risk factors for TLS include a high tumour burden, high concentrations of circulating cells ( 25,000/mm3), hypovolaemia, renal insufficiency, elevated pre-treatment uric acid levels and elevated lactate dehydrogenase levels. Management of TLS includes correction of electrolyte abnormalities, monitoring of renal function, maintenance of fluid balance and supportive care.

Progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) and death has been reported in CLL patients receiving cytotoxic pharmacotherapy, including ofatumumab. A diagnosis of PML should be considered in any Arzerra patient who reports the new onset of or changes in pre-existing neurologic signs and symptoms. If a diagnosis of PML is suspected Arzerra should be discontinued and referral to a neurologist should be considered.

Immunisations

The safety of, and ability to generate a primary or anamnestic response to, immunisation with live attenuated or inactivated vaccines during treatment with ofatumumab has not been studied. The response to vaccination could be impaired when B cells are depleted. Due to the risk of infection, administration of live attenuated vaccines should be avoided during and after treatment with ofatumumab, until B cell counts are normalised. The risks and benefits of vaccinating patients during therapy with ofatumumab should be considered.

Hepatitis B

Hepatitis B infection (HBV), including fatal infection, can occur in patients taking ofatumumab. Hepatitis B reactivation including fulminant hepatitis and death occurs with other monoclonal antibodies directed against CD20. Patients at high risk of HBV infection should be screened before initiation of Arzerra. Carriers of hepatitis B should be closely monitored for clinical and laboratory signs of active HBV infection during treatment with ofatumumab and for 6-12 months following the last infusion of Arzerra. Arzerra should be discontinued in patients who develop viral hepatitis, and appropriate treatment should be instituted. Insufficient data exist regarding the safety of administration of ofatumumab in patients with active hepatitis.

Cardiovascular

Patients with a history of cardiac disease should be monitored closely. Arzerra should be discontinued in patients who experience serious or life-threatening cardiac arrhythmias.

Bowel obstruction

Bowel obstruction has been reported in patients receiving anti-CD20 monoclonal antibody therapy, including ofatumumab. Patients who present with abdominal pain, especially early in the course of ofatumumab therapy, should be eva luated and appropriate treatment instituted.

Laboratory monitoring

Since