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Arzerra is a brand name for Ofatumumab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Previously untreated chronic lymphocytic leukaemia (CLL) Arzerra in combination with chlorambucil or bendamustine is indicated for the treatment of adult 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. Relapsed CLL…
Verbatim from this product's EMA label. Tap a section to expand.
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. Monitoring Patients should be closely monitored during administration of ofatumumab for the onset of infusion- related reactions, including cytokine release syndrome, particularly during the first infusion.
Pre-medication Patients should receive the following pre-medication medicinal products 30 minutes to 2 hours prior to each Arzerra infusion according to the following dosing schedules: Premedication schedule for Arzerra Previously untreated CLL or relapsed CLL Refractory CLL Infusion number 1 and 2 3 to n* 1 and 2 3 to 8 9 10 to 12 Intravenous corticosteroid (prednisolone or equivalent) 50 mg 0 to 50 mg** 100 mg 0 to 100 mg** 100 mg 50 to 100 mg*** Oral paracetamol (acetaminophen) 1000 mg Oral or intravenous antihistamine Diphenhydramine 50 mg or cetirizine 10 mg (or equivalent) *Up to 13 infusions in previously untreated CLL; up to 7 infusions in relapsed CLL **Corticosteroid may be either reduced or omitted for subsequent infusions at the discretion of the physician, if a severe infusion-related adverse drug reaction (ADR) did not occur with the preceding infusion(s).
***Corticosteroid may be reduced for subsequent infusions at the discretion of the physician, if a severe infusion-related ADR did not occur with the preceding infusion(s). Posology Previously untreated CLL For previously untreated CLL, the recommended dosage and schedule is: Cycle 1: 300 mg on day 1 followed 1 week later by 1000 mg on day 8 Subsequent cycles (until best response or a maximum of 12 cycles): 1000 mg on day 1 every 28 days.
Each cycle lasts 28 days and is counted from day 1 of the cycle. Medicinal product no longer authorised 4 Relapsed CLL For relapsed CLL, the recommended dosage and schedule is: Cycle 1: 300 mg on day 1 followed 1 week later by 1000 mg on day 8 Subsequent cycles (up to a maximum of 6 cycles in total): 1000 mg on day 1 every 28 days.
Each cycle lasts 28 days and is counted from day 1 of the cycle. Previously untreated CLL and relapsed CLL First infusion The initial rate of the first infusion of Arzerra should be 12 ml/h. 6). If an infusion-related ADR is observed during infusion, see below section “Dose modification and reinitiation of therapy after infusion-related ADRs”.
1). Medicinal product no longer authorised 9 Tabulated list of adverse reactions Adverse reactions reported in patients treated with ofatumumab as monotherapy and with ofatumumab in combination with chemotherapy, are listed below by MedDRA body system organ class and by frequency, using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (< 1/10,000); not known (cannot be estimated from available data).
Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness. Medicinal product no longer authorised 10 Description of selected adverse reactions Infusion-related reactions Of the 1,168 patients receiving ofatumumab in clinical trials for CLL, the most frequently observed ADRs were infusion-related reactions which occurred in 711 patients (61%) at any time during treatment.
The majority of infusion-related reactions were Grade 1 or Grade 2 in severity. Seven percent of patients had ≥Grade 3 infusion-related reactions at any time during treatment. Two percent of the infusion-related reactions led to discontinuation of treatment.
4). Infections Of the 1,168 patients receiving ofatumumab in clinical trials for CLL, 682 patients (58%) experienced an infection. These included bacterial, viral and fungal infections. 268 (23%) of the 1,168 patients experienced ≥Grade 3 infections.
65 (6%) of the 1,168 patients experienced a fatal infection. Neutropenia Of the 1,168 patients receiving ofatumumab in clinical trials, 420 patients (36%) experienced an adverse event associated with a decreased neutrophil count; 129 (11%) experienced a serious adverse event associated with a decreased neutrophil count.
In the pivotal study for untreated CLL (OMB110911; ofatumumab plus chlorambucil 217 patients, chlorambucil alone 227 patients), prolonged neutropenia (defined as Grade 3 or 4 neutropenia not resolved between 24 and 42 days after last dose of study treatment) was reported in 41 patients (9%) (23 patients [11%] treated with ofatumumab and chlorambucil, 18 patients [8%] treated with chlorambucil alone).
Infusion-related reactions Intravenous ofatumumab has been associated with infusion-related reactions. These reactions may result in temporary interruption or withdrawal of treatment. Pre-medication attenuates infusion-related reactions but these may still occur, predominantly during the first infusion.
g. myocardial ischaemia/infarction, bradycardia), chills/rigors, cough, cytokine release syndrome, diarrhoea, dyspnoea, fatigue, flushing, hypertension, hypotension, nausea, pain, pulmonary oedema, pruritus, pyrexia, rash, and urticaria.
In rare cases, these reactions may lead to death. Even with pre- medication, severe reactions, including cytokine release syndrome, have been reported following use of ofatumumab. Medicinal product no longer authorised 6 If an anaphylactic reaction occurs, Arzerra should be immediately and permanently discontinued and appropriate medical treatment should be initiated.
Infusion-related reactions occur predominantly during the first 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 Arzerra.
Tumour lysis syndrome In patients with CLL, tumour lysis syndrome (TLS) may occur with use of Arzerra. 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 Cases of progressive multifocal leukoencephalopathy (PML) resulting in death have been reported in CLL patients receiving cytotoxic pharmacotherapy, including ofatumumab.
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6). If an infusion-related ADR is observed during infusion, see below section “Dose modification and reinitiation of therapy after infusion-related ADRs”. Dose modification and reinitiation of therapy after infusion-related ADRs In the event of a mild or moderate ADR, the infusion should be interrupted and restarted at half of the infusion rate at the time of interruption once the patient’s condition is stable.
If the infusion rate had not been increased from the starting rate of 12 ml/hour prior to interrupting due to an ADR, the infusion should be restarted at 12 ml/hour, the standard starting infusion rate. The infusion rate can continue to be increased according to standard procedures, to physician discretion and to patient tolerance (not to exceed doubling the rate every 30 minutes).
In the event of a severe ADR, the infusion should be interrupted and restarted at 12 ml/hour when the patient’s condition is stable. The infusion rate can continue to be increased according to standard procedures, to physician discretion and to patient tolerance (not to exceed increasing the rate every 30 minutes).
Arzerra should be permanently discontinued in patients who develop an anaphylactic reaction to the medicinal product. Refractory CLL The recommended dose and schedule is 12 doses administered as follows: 300 mg on day 1 followed 1 week later by 2000 mg weekly for 7 doses (infusions 2 to 8) followed 4-5 weeks later by 2000 mg every 28 days for 4 doses (infusions 9 to 12) First and second infusions The initial rate of the first and second infusion of Arzerra should be 12 ml/hour.
6). If an infusion-related ADR is observed during an infusion, see below section “Dose modification and reinitiation of therapy after infusion-related ADRs”. 6). Medicinal product no longer authorised 5 Dose modification and reinitiation of therapy after infusion-related ADRs In the event of a mild or moderate ADR, the infusion should be interrupted and restarted at half of the infusion rate at the time of interruption, once the patient’s condition is stable.
If the infusion rate had not been increased from the starting rate of 12 ml/hour prior to interrupting due to an ADR, the infusion should be restarted at 12 ml/hour, the standard starting infusion rate. The infusion rate can continue to be increased according to standard procedures, to physician discretion and to patient tolerance (not to exceed doubling the rate every 30 minutes).
In the event of a severe ADR, the infusion should be interrupted and restarted at 12 ml/hour, once the patient’s condition is stable. The infusion rate can […]
Nine patients (4%) treated with ofatumumab and chlorambucil, and three patients treated with chlorambucil alone had late-onset neutropenia (defined as Grade 3 or 4 neutropenia starting at least 42 days after the last treatment). In the pivotal study (OMB110913, ofatumumab plus fludarabine and cyclophosphamide 181 patients; fludarabine and cyclophosphamide 178 patients) in relapsed CLL patients, prolonged neutropenia was reported in 38 (11%) patients (18 patients [10%] treated with ofatumumab in combination with fludarabine and cyclophosphamide compared to 20 patients [11%] in the fludarabine and cyclophosphamide arm).
Thirteen (7%) patients treated with ofatumumab in combination with fludarabine and cyclophosphamide, and 5 (3%) patients treated with fludarabine and cyclophosphamide had late-onset neutropenia. Cardiovascular The effect of multiple doses of Arzerra on the QTc interval was evaluated in a pooled analysis of three open-label studies in patients with CLL (N=85).
Increases above 5 msec were observed in the median/mean QT/QTc intervals in the pooled analysis. e. >20 milliseconds) were detected. None of the patients had an increase of QTc to >500 msec. A concentration dependent increase in QTc was not detected.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
A diagnosis of PML should be considered in any Arzerra patient who reports the new onset of or changes in pre-existing neurological 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 Arzerra therapy should be considered.
Hepatitis B Hepatitis B virus (HBV) infection and reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, has occurred in patients treated with medicinal products classified as CD20- directed cytolytic antibodies, including Arzerra.
Cases have been reported in patients who are hepatitis B surface antigen (HBsAg) positive and also in those who are hepatitis B core antibody (anti-HBc) positive but HBsAg negative. e. HBsAg negative, anti-HBc positive, and hepatitis B surface antibody [anti- HBs] positive).
HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive. e. increase in transaminase levels and, in severe cases, increase in bilirubin levels, liver failure, and death.
All patients should be screened for HBV infection by measuring HBsAg and anti-HBc before initiation of Arzerra treatment. For patients who show evidence of prior (HBsAg negative, anti-HBc positive) hepatitis B infection, physicians with expertise in managing hepatitis B should be consulted regarding monitoring and initiation of HBV antiviral therapy.
Medicinal product no longer authorised 7 Patients with evidence of prior HBV infection should be monitored for clinical and laboratory signs of hepatitis or HBV reactivation during treatment with and for 6-12 months following the last infusion of Arzerra.
HBV reactivation has been reported up to 12 months following completion of therapy. Discontinuation of HBV antiviral therapy should be discussed with physicians with expertise in managing hepatitis B. In patients who develop reactivation of HBV while receiving Arzerra, Arzerra and any concomitant chemotherapy should be interrupted immediately, and appropriate treatment instituted.
Insufficient data exist regarding the safety of resuming Arzerra in patients who develop HBV reactivation. Resumption of Arzerra in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing hepatitis B.
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. The effect of multiple doses of Arzerra on the QTc interval was evaluated in a pooled analysis of three open-label studies in patients with CLL (N=85).
Increases above 5 msec were observed in the median/mean QT/QTc intervals in the pooled analysis. e. >20 milliseconds) were detected. None of the patients had an […]