Adverse reactions are listed below by MedDRA body system organ class and by frequency. 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, undesirable effects are presented in order of decreasing seriousness.

MedDRA System Organ Class
 Very common
 Common
 Uncommon
 
Infections and Infestations
 Lower respiratory tract infection, including pneumonia, upper respiratory tract infection
 Sepsis, including neutropenic sepsis and septic shock, herpes virus infection, urinary tract infection
  
Blood and lymphatic system disorders
 Neutropenia, anaemia
 Febrile neutropenia, thrombocytopenia, leukopenia
 Agranulocytosis, coagulopathy, red cell aplasia, lymphopenia
 
Immune system disorders
   Anaphylactoid reactions, hypersensitivity
  
Metabolism and nutrition disorders
     Tumour lysis syndrome
 
Cardiac disorders
   Tachycardia
  
Vascular disorders
   Hypotension, hypertension
  
Respiratory, thoracic and mediastinal disorders
   Bronchospasm, hypoxia, dyspnoea, chest discomfort, pharyngolaryngeal pain, cough, nasal congestion
  
Gastrointestinal disorders
   Small bowel obstruction, diarrhoea, nausea
  
Skin and subcutaneous tissue disorders
 Rash
 Urticaria, pruritus, flushing
  
Musculoskeletal and connective tissue disorders
   Back pain
  
General disorders and administration site conditions
   Cytokine release syndrome, pyrexia, rigors, chills, hyperhidrosis, fatigue

Infusion reactions: In the pivotal study (Hx-CD20-406), infusion reactions occurred in 44% of patients on the day of the first infusion (300 mg), 29% on the day of the second infusion (2,000 mg), and less frequently during subsequent infusions (see section 4.4).

Infections: In the pivotal study, a total of 108 patients (70%) experienced bacterial, viral, or fungal infections. A total of 45 patients (29%) experienced  Grade 3 infections, of which 19 (12%) were fatal. The proportion of fatal infections in the indicated fludarabine- and alemtuzumab-refractory group was 17%.

Neutropenia: Of 108 patients with normal neutrophil counts at baseline who were part of the pivotal study, 45 (42%) developed  Grade 3 neutropenia. Nineteen (18%) developed Grade 4 neutropenia. Some patients experienced new onset Grade 4 neutropenia > 2 weeks in duration.

4.9 Overdose

 No case of overdose has been reported.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

 Pharmacotherapeutic group: monoclonal antibodies, ATC code: L01XC10

This medicinal product has been authorised under a so-called 'conditional approval' scheme.

This means that further evidence on this medi