4.7 Effects on ability to drive and use machines

 No studies on the effects on the ability to drive and use machines have been performed. However, there is no evidence that Avastin treatment results in an increase in adverse events that might lead to impairment of the ability to drive or operate machinery or impairment of mental ability.

4.8 Undesirable effects
 The overall safety profile of Avastin is based on data from over 3,500 patients with various malignancies, predominantly treated with Avastin in combination with chemotherapy in clinical trials.

The most serious adverse reactions were:

• Gastrointestinal perforations (see section 4.4).

• Haemorrhage, including pulmonary haemorrhage/haemoptysis, which is more common in non-small cell lung cancer patients (see section 4.4).

• Arterial thromboembolism (see section 4.4).

The most frequently observed adverse reactions across clinical trials in patients receiving Avastin were hypertension, fatigue or asthenia, diarrhoea and abdominal pain.

Analyses of the clinical safety data suggest that the occurrence of hypertension and proteinuria with Avastin therapy are likely to be dose-dependent.

Table 1 lists adverse reactions associated with the use of Avastin in combination with different chemotherapy regimens in multiple indications. These reactions had occurred either with at least a 2% difference compared to the control arm (NCI-CTC grade 3-5 reactions) or with at least a 10% difference compared to the control arm (NCI-CTC grade 1-5 reactions), in at least one of the major clinical trials.

The adverse reactions listed in this table fall into the following categories: Very Common ( 1/10) and Common ( 1/100 - < 1/10). Adverse reactions are added to the appropriate category in the table below according to the highest incidence seen in any of the major clinical trials.

Within each frequency grouping adverse reactions are presented in the order of decreasing seriousness. Some of the adverse reactions are reactions commonly seen with chemotherapy, (e.g. palmar-plantar erythrodysaesthesia syndrome with capecitabine and peripheral sensory neuropathy with paclitaxel or oxaliplatin); however, an exacerbation by Avastin therapy can not be excluded.
Table 1 Very common and common adverse reactions

System organ class (SOC)
 NCI-CTC grade 3-5 reactions

( 2% difference between the trial arms in at least one clinical trial)
 All grade reactions

( 10% difference between the trial arms in at least one clinical trial)
 

Very common

 
Common

 
Very common

 
Infections and infestations
   Sepsis

Abscess

Infection
  
Blood and the lymphatic systems disorders
 Febrile neutropenia

Leucopenia

Thrombocytopenia

Neutropenia
 Anaemia
  
Metabolism and nutrition disorders
   Dehydration
 Anorexia
 
Nervous system disorders
 Peripheral sensory neuropathy
 Cerebrovascular accident

Syncope

Somnolence

Headache
 Dysgeusia

Headache
 
Eye disorders
     Ey