1. Name of the medicinal product
Arzerra® 100 mg concentrate for solution for infusion.
Arzerra® 1,000 mg concentrate for solution for infusion.
2. Qualitative and quantitative composition
AND QUANTITATIVE COMPOSITION
One ml of concentrate contains 20 mg of ofatumumab.
Each vial contains 100 mg of ofatumumab in 5 ml.
Each vial contains 1,000 mg of ofatumumab in 50 ml.
Ofatumumab is a human monoclonal antibody produced in a recombinant murine cell line (NS0).
Excipient(s) with known effect:
This medicinal product contains 34.8 mg sodium per 300 mg dose, 116 mg sodium per 1,000 mg dose and 232 mg sodium per 2,000 mg dose.
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Concentrate for solution for infusion (sterile concentrate).
Clear to opalescent, colourless to pale yellow liquid.
4. Clinical particulars
4.1 Therapeutic indications
Previously untreated chronic lymphocytic leukaemia (CLL):
Arzerra in combination with chlorambucil or bendamustine is indicated for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.
See section 5.1 for further information.
Refractory CLL:
Arzerra is indicated for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab.
See section 5.1 for further information.
4.2 Posology and method of administration
Arzerra should be administered under the supervision of a physician experienced in the use of cancer therapy and in an environment where full resuscitation facilities are immediately available.
Pre-medication
Patients should be pre-medicated 30 minutes to 2 hours prior to Arzerra infusion according to the following dosing schedules:
Previously untreated CLL:
• oral paracetamol (acetaminophen) 1,000 mg (or equivalent), plus
• oral or intravenous antihistamine (diphenhydramine 50 mg or cetirizine 10 mg or equivalent), plus
• intravenous corticosteroid (prednisolone 50 mg or equivalent).
Following the first and second infusion, if the patient does not experience a severe adverse drug reaction (ADR), pre-medication with a corticosteroid for subsequent infusions may either be reduced or omitted, at the discretion of the physician.
Refractory CLL:
• oral paracetamol (acetaminophen) 1,000 mg (or equivalent), plus
• oral or intravenous antihistamine (diphenhydramine 50 mg or cetirizine 10 mg or equivalent), plus
• intravenous corticosteroid (prednisolone 100 mg or equivalent).
If the second weekly infusion is completed without a severe ADR, the dose of the corticosteroid may be reduced for infusion numbers 3 through 8, at the discretion of the physician.
Prior to the ninth infusion (first monthly infusion), patients should receive the full dose of premedication agents described above. If the ninth infusion is completed without a severe ADR, the dose may be reduced to the equivalent of 50 mg prednisolone for subsequent infusions at the discretion of the physician.
Posology
Previously untreated CLL:
The recommended dose and schedule is 300 mg on day 1 followed 1 week later by 1,000 mg on day 8 (cycle 1), followed by 1,000 mg on day 1 of subsequent cycles, for a minimum of 3 cycles, until best response or a maximum of 12 cycles (every 28 days).
Best response is a clinical response that did not improve with 3 additional cycles of treatment.
First infusion
The initial rate of the first infusion of Arzerra should be 12 ml/h. During infusion, the rate should be increased every 30 minutes to a maximum of 400 ml/h (see section 6.6).
Subsequent infusions
If the first infusion has been completed without severe infusion related ADRs, the subsequent infusions can start at a rate of 25 ml/h and should be increased every 30 minutes up to a maximum of 400 ml/h (see section 6.6).
Refractory CLL:
The recommended dose is 300 mg for the first infusion and 2,000 mg for all subsequent infusions. The infusion schedule is 8 consecutive weekly infusions, followed 4-5 weeks later by 4 consecutive monthly (i.e. every 4 weeks) infusions.
First and second infusions
The initial rate of the first and second infusion of Arzerra should be 12 ml/hour. During infusion, the rate should be increased every 30 minutes to a maximum of 200 ml/hour (see section 6.6).
Subsequent infusions
If the second infusion has been completed without severe infusion related ADRs, the remaining infusions can start at a rate of 25 ml/hour and should be increased every 30 minutes up to a maximum of 400 ml/hour (see section 6.6).
Dose modification and reinitiation of therapy for infusion related ADRs – in patients with previously untreated CLL and refractory CLL.
Interrupt infusion for infusion related ADRs of any severity. Treatment can be resumed at the discretion of the treating physician. The following infusion rate modifications can be used as a guide:
• In case of a mild or moderate ADR, the infusion should be interrupted and restarted at half of the infusion rate at the time of interruption, when th