Lacrimation increased
 
Cardiac disorders
   Cardiac failure congestive

Supraventricular tachycardia
  
Vascular disorders
 Hypertension
 Thromboembolism (arterial)*

Deep vein thrombosis

Haemorrhage
 Hypertension
 
Respiratory, thoracic and mediastinal disorders
   Pulmonary embolism

Dyspnoea

Hypoxia

Epistaxis
 Dyspnoea

Epistaxis

Rhinitis
 
Gastrointestinal disorders
 Diarrhoea

Nausea

Vomiting
 Intestinal Perforation

Ileus

Intestinal obstruction

Abdominal pain

Gastrointestinal disorder

Stomatitis
 Constipation

Stomatitis

Rectal haemorrhage
 
Endocrine disorders
     Ovarian failure**
 
Skin and subcutaneous tissue disorders
   Palmar-plantar erythrodysaesthesia syndrome
 Exfoliative dermatitis

Dry skin

Skin discolouration
 
Musculoskeletal, connective tissue and bone disorders
   Muscular weakness

Myalgia
 Arthralgia
 
Renal and urinary disorders
   Proteinuria

Urinary Tract Infection
 Proteinuria
 
General disorders and administration site conditions
 Asthenia

Fatigue
 Pain

Lethargy

Mucosal inflammation
 Pyrexia

Asthenia

Pain

Mucosal inflammation

* Pooled arterial thromboembolic events including cerebrovascular accident, myocardial infarction, transient ischaemic attack and other arterial thromboembolic events.

Data are unadjusted for the differential time on treatment.

** Based on a substudy from NSABP C-08 with 295 patients

Further information on selected serious adverse reactions

Gastrointestinal perforations (see section 4.4)

Avastin has been associated with serious cases of gastrointestinal perforation.

Gastrointestinal perforations have been reported in clinical trials with an incidence of less than 1% in patients with metastatic breast cancer or non-squamous non-small cell lung cancer, and up to 2.0% in metastatic colorectal cancer patients. Fatal outcome was reported in approximately a third of serious cases of gastrointestinal perforations, which represents between 0.2%-1% of all Avastin treated patients.

The presentation of these events varied in type and severity, ranging from free air seen on the plain abdominal X-ray, which resolved without treatment, to intestinal perforation with abdominal abscess and fatal outcome. In some cases underlying intra-abdominal inflammation was present, either from gastric ulcer disease, tumour necrosis, diverticulitis, or chemotherapy-associated colitis.

Fistulae (see section 4.4)

Avastin use has been associated with serious cases of fistulae including events resulting in death.

In clinical trials, gastrointestinal fistulae have been reported with an incidence of up to 2% in patients with metastatic colorectal cancer, but were also reported less commonly in patients with other types of cancers. Uncommon ( 0.1% to < 1%) reports of other types of fistulae that involve areas of the body other than the gastrointestinal tract (e.g. bronchopleural, urogenital and biliary fistula