Medicinal Products

ARZERRA 1,000 mg

Generic drug of the therapeutic class: Oncology and Hematology
Active ingredients: Ofatumumab
laboratory: Glaxo Group Ltd

Solution for solution for IV infusion
Box of 1 bottle of 50 ml
All forms

Indication

Chronic Leukemelymphoid (CLL) not previously treated:

Arzerra is indicated in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior treatment and who are not eligible for fludarabine therapy.

See section Pharmacodynamic properties for more information.

Refractory LLC:

Arzerra is indicated for the treatment of CLL in patients refractory to fludarabine and alemtuzumab.

Dosage ARZERRA 1000 mg concentrate for solution for infusion IV Box of 1 bottle of 50 ml

Arzerra should be administered under the supervision of a physician experienced in the use of cancer treatment and in an environment where all means of resuscitation are immediately available.

Premedication

Patients should be premedicated between 30 minutes and 2 hours prior to infusion of Arzerra, according to the following regimens:

LLC not previously treated:

• paracetamol (acetaminophen) orally at a dose of 1000 mg (or equivalent), and

• anti-histamine oral or intravenous (50 mg diphenhydramine or 10 mg cetirizine or equivalent), as well as,

• intravenous corticosteroid (50 mg prednisolone or equivalent).

If no serious adverse effects (AEs) are observed after the first and second infusions, the physician may decide to reduce or discontinue premedication with corticosteroids for subsequent infusions.

Refractory LLC:

• paracetamol (acetaminophen) orally at a dose of 1000 mg (or equivalent), and

• anti-histamine oral or intravenous (50 mg diphenhydramine or 10 mg cetirizine or equivalent), as well as,

• intravenous corticosteroid (100 mg prednisolone or equivalent).

If no serious AE is observed at the end of the second weekly infusion, the doctor may decide to reduce the dose of corticosteroid from the third to the eighth infusion. Prior to the ninth infusion (first monthly infusion), patients should receive the full dose of premedication therapy, according to the dosing regimen described above. If no serious AE is observed after the ninth infusion, the physician may decide to reduce the dose of corticosteroids to 50 mg prednisolone, or equivalent, for subsequent infusions.

Dosage

LLC not previously treated:

The recommended regimen is 300 mg on the first day, followed by 1000 mg one week later, on the eighth day (cycle 1), then 1000 mg on the first day of each subsequent cycle, for a minimum of 3 cycles, until 'to obtain the best response to treatment, or a maximum of 12 cycles (every 28 days).

The best response is the clinical response that has not improved after 3 additional cycles of treatment.

First infusion

The first infusion of Arzerra should be initiated at a rate of 12 ml / h. During the infusion, the flow rate should be increased every 30 minutes to a maximum of 400 ml / h (see section Instructions for use, handling and disposal ).

Following infusions

If the first infusion has not been accompanied by any serious infusion-related AE, subsequent infusions may be initiated at a flow rate of 25 ml / h. The flow rate should then be increased every 30 minutes to a maximum of 400 ml / h (see section Instructions for use, handling and disposal ).

Refractory LLC:

The recommended dose is 300 mg for the first infusion and 2000 mg for all subsequent infusions. The infusions are given as a weekly infusion for 8 consecutive weeks, followed 4 to 5 weeks later, by one infusion per month for 4 consecutive months (i.e., every 4 weeks).

First and second infusions

The first and second infusions of Arzerra should be initiated at a rate of 12 ml / hr. During the infusion, the flow rate should be increased every 30 minutes to a maximum of 200 ml / h (see section Instructions for use, handling and disposal ).

Following infusions

If the second infusion was not accompanied by any serious infusion-related AE, the following infusions can be initiated at a flow rate of 25 ml / h. The flow rate should then be increased every 30 minutes to a maximum of 400 ml / h (see section Instructions for use, handling and disposal ).

Dose Modification and Treatment Reinitialization for Infusion-Related AEs - in patients with previously untreated CLL and refractory CLL

Discontinue infusion for infusion-related AE, regardless of severity. The attending physician may decide to resume treatment. The infusion rate changes described below may be used as a guide:

• In mild to moderate AE, infusion should be interrupted and resumed at a rate that is halved relative to the time of discontinuation, when the patient's condition is stable. If the initial infusion rate of 12 ml / h has not been increased prior to an AE arrest, the infusion should be restarted at a rate of 12 ml / h, the standard rate of initial infusion rate. The infusion rate may continue to be increased according to standard procedures, at the discretion of the physician and depending on the patient's tolerance (without increasing this rate more frequently than every 30 minutes).

• In case of severe AE, infusion should be stopped and restarted at a rate of 12 ml / h, when the patient's condition is stable. The infusion rate may continue to be increased according to standard procedures, at the discretion of the physician and depending on the patient's tolerance (without increasing this rate more frequently than every 30 minutes).

Pediatric population

Due to insufficient safety and / or efficacy data, the use of Arzerra is not recommended for children under 18 years of age.

Elderly

No significant differences in safety and efficacy have been reported according to the age of the patient (see section 5.1 Pharmacodynamic properties ). Based on available safety and efficacy data in the elderly, no dose adjustment is necessary (see section 5.2 ).

Renal failure

No specific studies have been conducted with Arzerra in patients with renal impairment. No dose adjustment is recommended in patients with mild to moderate renal impairment (creatinine clearance> 30 ml / min) (see section 5.2 ).

Hepatic insufficiency

No specific studies have been conducted with Arzerra in patients with hepatic impairment. However, it is unlikely that a dose modification will be necessary in these patients (see section Pharmacokinetic properties ).

Administration mode

Arzerra is administered by intravenous infusion and should be diluted before administration. For instructions on drug dilution before administration, see Instructions for Use, Handling and Disposal .

Against indications

Hypersensitivity to ofatumumab or to any of the excipients listed under Composition .

Arzerra side effects

Summary of the security profile

The overall safety profile of ofatumumab in CLL (previously untreated, relapsed, or refractory) is based on data collected from 511 patients in clinical trials (see section 5.1 Pharmacodynamic properties ). Of these patients, 250 were treated with ofatumumab alone (patients with relapsed or refractory CLL) and 261 with ofatumumab in combination with an alkylating agent (patients with previously untreated CLL not eligible for fludarabine treatment). .

Tabulated summary of adverse effects

Adverse reactions reported with ofatumumab, alone or in combination with an alkylating agent, are listed by organ class (MedDRA classification) and by frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1/10 000) at <1/1000), very rare (<1 / 10, 000) and frequency not known (can not be estimated from the available data). Within each frequency group, adverse effects are presented in descending order of severity.

convention

MedDRA

Very common

Frequent

Rare

Rare

Infections and infestations Infection of the lower respiratory tract, including pneumonia, upper respiratory tract infection Sepsis, including neutropenic sepsis and septic shock, herpesvirus infection, urinary tract infection HBV infection and reactivation of HBV
Blood and lymphatic system disorders Neutropenia, anemia Febrile neutropenia, thrombocytopenia, leukopenia Agranulocytosis, disorders of coagulation, erythroblastopenia, lymphopenia
Immune system disorders Anaphylactoid reactions *, hypersensitivity * Anaphylactic shock*
Metabolism and nutrition disorders Tumor lysis syndrome
Heart conditions tachycardia *
Vascular disorders Hypotension *, hypertension *
Respiratory, thoracic and mediastinal disorders Bronchospasm *, hypoxia *, dyspnea e *, chest discomfort *, pharyngolaryngeal pain *, cough *, nasal congestion *
Gastrointestinal disorders Nausea * Diarrhea* Occlusion of the small intestine
Skin and subcutaneous tissue disorders rash * Urticaria *, pruritus *, redness *
Musculoskeletal and systemic disorders Back pain *
General disorders and administration site conditions Fever *

Cytokine release syndrome *, tremor *, chills *, hyperhidrosis *,
tired*

* These events may be attributable to ofatumumab as part of an infusion-related reaction, typically occurring after the start of the infusion and within 24 hours of completion of the infusion (see Warnings and Precautions section). employment ).

Description of some adverse effects

Infusion-related reactions

The most common adverse events observed in patients treated with ofatumumab in clinical trials were infusion-related reactions in 68% (348/511) of patients at any time during treatment. The majority of infusion-related reactions were grade 1 or grade 2. Eight percent of patients experienced a grade ≥3 infusion reaction at any time during treatment. Two percent of the infusion-related reactions required discontinuation of treatment. No reaction related to the perfusion of fatal outcome has been reported (see Warnings and Precautions ).

infections

Of the 511 patients treated with ofatumumab in clinical trials, 300 (59%) had an infection, including bacterial, viral, or fungal infections. One hundred and four (20%) of the 511 patients had grade ≥3 infections. Twenty-eight (5%) of the 511 patients had a life-threatening infection.

neutropenia

Of the 511 patients treated with ofatumumab in clinical trials, 139 (27%) experienced an adverse event associated with decreased neutrophils; 118 (23%) of the 511 patients experienced grade ≥3 adverse events associated with decreased neutrophils. Forty-two (8%) experienced a serious adverse event associated with decreased neutrophils.

In a pivotal study in patients with previously untreated CLL (OMB110911), prolonged neutropenia (defined as unresolved Grade 3 or 4 neutropenia between 24 and 42 days after the last dose) was reported in 41 patients ( 23 patients treated with ofatumumab in combination with chlorambucil, and 18 patients treated with chlorambucil alone). Late neutropenia, defined as grade 3 or 4 neutropenia occurring at least 42 days after the last dose, was reported in nine patients treated with ofatumumab in combination with chlorambucil, and three patients treated with chlorambucil alone.

Cardiovascular effects

The effect of multiple dose administration of Arzerra on the QTc interval was evaluated in a pooled analysis of three open-label clinical studies in patients with CLL (N = 85). In this pooled analysis, median / mean QT / QTc interval prolongations of more than 5 msec were observed. No significant changes in the mean QTc interval (ie> 20 milliseconds) were observed. No patients had QTc prolongation> 500 msec. No prolongation of the QTc dependent concentration was detected.

Reporting of suspected adverse reactions

The reporting of suspected adverse reactions after authorization of the drug is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the national reporting system - see Annex V.

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