Sign Out
GENERAL: In order to improve traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded (or stated) in the patient file.
Gastrointestinal Perforations and Fistulae: Patients may be at increased risk for the development of gastrointestinal perforation (see also CLINICAL TRIALS under Adverse Reactions) and gallbladder perforation (see also POSTMARKETING EXPERIENCE under Adverse Reactions) when treated with Avastin. Avastin should be permanently discontinued in patients who develop gastrointestinal perforation. Patients treated for persistent, recurrent, or metastatic cervical cancer with Avastin may be at increased risk of fistulae between the vagina and any part of the GI tract (Gastrointestinal-vaginal fistulae) (see CLINICAL TRIALS: Description of selected adverse drug reactions from clinical trials: Gastrointestinal Perforation and fistulae under Adverse Reactions).
Non-GI Fistulae (see CLINICAL TRIALS under Adverse Reactions): Patients may be at increased risk for the development of fistulae when treated with Avastin (see CLINICAL TRIALS under Adverse Reactions).
Permanently discontinue Avastin in patients with tracheoesophageal (TE) fistula or any Grade 4 fistula. Limited information is available on the continued use of Avastin in patients with other fistulae. In cases of internal fistula not arising in the GI tract, discontinuation of Avastin should be considered.
Haemorrhage (see CLINICAL TRIALS under Adverse Reactions): Patients treated with Avastin have an increased risk of haemorrhage, especially tumour-associated haemorrhage (see CLINICAL TRIALS: Description of selected adverse drug reactions from clinical trials: Haemorrhage under Adverse Reactions). Avastin should be permanently discontinued in patients who experience Grade 3 or 4 bleeding during Avastin therapy.
Patients with untreated CNS metastases were routinely excluded from clinical trials with Avastin, based on imaging procedures or signs and symptoms. Therefore, the risk of CNS haemorrhage in such patient has not been prospectively evaluated in randomised clinical studies (see CLINICAL TRIALS: Description of selected adverse drug reactions from clinical trials: Haemorrhage under Adverse Reactions). Patients should be monitored for signs and symptoms of CNS bleeding, and Avastin treatment discontinued in cases of intracranial bleeding.
There is no information on the safety profile of Avastin in patients with congenital bleeding diathesis, acquired coagulopathy or in patients receiving full dose of anticoagulants for the treatment of thromboembolism prior to starting Avastin treatment, as such patients were excluded from clinical trials. Therefore, caution should be exercised before initiating Avastin therapy in these patients. However, patients who developed venous thrombosis while receiving Avastin therapy did not appear to have an increased rate of Grade 3 or above bleeding when treated with full dose of warfarin and Avastin concomitantly.
Severe Eye Infections Following Compounding for Unapproved Intravitreal Use (see POSTMARKETING EXPERIENCE under Adverse Reactions): Individual cases and clusters of serious ocular adverse events have been reported (including infectious endophthalmitis and other ocular inflammatory conditions) following unapproved intravitreal use of Avastin compounded from vials approved for intravenous administration in cancer patients. Some of these events have resulted in various degrees of visual loss, including permanent blindness.
Pulmonary Haemorrhage/Haemoptysis (see Adverse Reactions): Patients with non-small cell lung cancer treated with Avastin may be at risk for serious, and in some cases fatal, pulmonary haemorrhage/haemoptysis (see CLINICAL TRIALS: Description of selected adverse drug reactions from clinical trials: Haemorrhage under Adverse Reactions). Patients with recent pulmonary haemorrhage/haemoptysis (>½ teaspoon red blood) should not be treated with Avastin.
Hypertension: An increased incidence of hypertension was observed in patients treated with Avastin. Clinical safety data suggest that the incidence of hypertension is likely to be dose-dependent. Pre-existing hypertension should be adequately controlled before starting Avastin treatment. There is no information on the effect of Avastin in patients with uncontrolled hypertension at the time of initiating Avastin therapy. Monitoring of blood pressure is recommended during Avastin therapy (see CLINICAL TRIALS under Adverse Reactions).
In most cases hypertension was controlled adequately using standard antihypertensive treatment appropriate for the individual situation of the affected patient. Avastin should be permanently discontinued if medically significant hypertension cannot be adequately controlled with antihypertensive therapy, or if, the patient develops hypertensive crisis or hypertensive encephalopathy (see CLINICAL TRIALS and POSTMARKETING EXPERIENCE under Adverse Reactions).
Posterior Reversible Encephalopathy Syndrome (PRES): There have been rare reports of Avastin-treated patients developing signs and symptoms that are consistent with Posterior Reversible Encephalopathy Syndrome (PRES), a rare neurological disorder, which can present with the following signs and symptoms among others: seizures, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). In patients developing PRES, treatment of specific symptoms including control of hypertension is recommended along with discontinuation of Avastin. The safety of reinitiating Avastin therapy in patients previously experiencing PRES is not known (see CLINICAL TRIALS and POSTMARKETING EXPERIENCE under Adverse Reactions).
Arterial Thromboembolism: In clinical trials, the incidence of arterial thromboembolism events including cerebrovascular accidents, transient ischaemic attack (TIA) and myocardial infarction (MI) was higher in patients receiving Avastin in combination with chemotherapy compared to those who received chemotherapy alone.
Avastin should be permanently discontinued in patients who develop arterial thromboembolic events.
Patients receiving Avastin plus chemotherapy with a history of arterial thromboembolism, diabetes or age greater than 65 years have an increased risk of developing arterial thromboembolic events during Avastin therapy. Caution should be taken when treating such patients with Avastin.
Venous Thromboembolism (see Adverse Reactions): Patients may be at risk of developing venous thromboembolic events, including pulmonary embolism under Avastin treatment.
Patients treated for persistent, recurrent, or metastatic cervical cancer with Avastin may be at increased risk of venous thromboembolic events (see CLINICAL TRIALS: Description of selected adverse drug reactions from clinical trials: Thromboembolism: Venous thromboembolism under Adverse Reactions).
Avastin should be discontinued in patients with life-threatening (Grade 4) venous thromboembolic events, including pulmonary embolism. Patients with thromboembolic events ≤ Grade 3 need to be closely monitored.
Congestive Heart Failure (see Adverse Reactions): Events consistent with congestive heart failure (CHF) were reported in clinical trials. The findings ranged from asymptomatic declines in left ventricular ejection fraction to symptomatic CHF, requiring treatment or hospitalisation.
Caution should be exercised when treating patients with clinically significant cardiovascular disease such as pre-existing coronary artery disease, or congestive heart failure with Avastin.
Most of the patients who experienced CHF had metastatic breast cancer and had received previous treatment with anthracyclines, prior radiotherapy to the left chest wall or other risk factors for CHF were present.
In patients in AVF3694g who received treatment with anthracyclines and who had not received anthracyclines before, no increased incidence of all grade CHF was observed in the anthracycline + bevacizumab group compared to the treatment with anthracyclines only. In both AVF3694g and AVF3693g, CHF grade 3 or higher events were somewhat more frequent among patients receiving bevacizumab in combination with chemotherapy than in patients receiving chemotherapy alone. This is consistent with results in patients in other studies of metastatic breast cancer who did not receive concurrent anthracycline treatment (see CLINICAL TRIALS under Adverse Reactions).
Neutropenia: Increased rates of severe neutropenia, febrile neutropenia, or infection with severe neutropenia (including some fatalities) have been observed in patients treated with some myelotoxic chemotherapy regimens plus Avastin in comparison to chemotherapy alone.
Wound Healing: Avastin may adversely affect the wound healing process. Serious wound healing complications with a fatal outcome have been reported.
Avastin therapy should not be initiated for at least 28 days following major surgery or until the surgical wound is fully healed. In patients who experience wound healing complications during Avastin treatment, Avastin should be withheld until the wound is fully healed. Avastin therapy should be withheld for elective surgery (see CLINICAL TRIALS under Adverse Reactions).
Necrotising fasciitis including fatal cases, has rarely been reported in patients treated with Avastin; usually secondary to wound healing complications, gastrointestinal perforation or fistula formation. Avastin therapy should be discontinued in patients who develop necrotising fasciitis, and appropriate treatment should be promptly initiated (see also POSTMARKETING EXPERIENCE under Adverse Reactions).
Proteinuria (see Adverse Reactions): In clinical trials, the incidence of proteinuria was higher in patients receiving Avastin in combination with chemotherapy compared to those who received chemotherapy alone. Grade 4 proteinuria (nephrotic syndrome) was seen in up to 1.4% of patients treated with Avastin. In the event of nephrotic syndrome, Avastin treatment should be permanently discontinued.
Hypersensitivity reactions, anaphylactic reactions (including anaphylactic shock), infusion reactions (see CLINICAL TRIALS and POSTMARKETING EXPERIENCE under Adverse Reactions): Patients may be at risk of developing hypersensitivity reactions, anaphylactic reactions (including anaphylactic shock), and infusion-related reactions. Close observation of the patient during and following the administration of bevacizumab is recommended. If an anaphylactic reaction occurs, the infusion should be permanently discontinued and appropriate medical therapies should be administered.
If an infusion-related reactions occurs, treatment should be temporarily interrupted until resolution of symptoms. Permanently discontinue Avastin for severe (Grade ≥3) infusion related-reaction. A systematic premedication is not warranted.
Ovarian Failure/Fertility (see FEMALES AND MALES OF REPRODUCTIVE POTENTIAL under Use in Pregnancy & Lactation and CLINICAL TRIALS under Adverse Reactions): Avastin may impair female fertility. Therefore, fertility preservation strategies should be discussed with women of child-bearing potential prior to starting treatment with Avastin.
DRUG ABUSE AND DEPENDENCE: Not applicable.
RENAL IMPAIRMENT: The safety and efficacy of Avastin has not been studied in patients with renal impairment.
HEPATIC IMPAIRMENT: The safety and efficacy of Avastin has not been studied in patients with hepatic impairment.
ABILITY TO DRIVE AND USE MACHINES: No studies on the effects on the ability to drive and use machine 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.
USE IN CHILDREN: Avastin is not approved for use in patients under the age of 18 years. The safety and efficacy of Avastin in this population have not been established. Addition of Avastin to standard of care did not demonstrate clinical benefit in pediatric patients in two phase II clinical trials: one in pediatric high grade glioma and one in pediatric metastatic rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma.
In published reports, cases of osteonecrosis at sites other than the jaw have been observed in patients under the age of 18 years exposed to Avastin (see POSTMARKETING EXPERIENCE under Adverse Reactions and Pharmacology: Toxicology: Nonclinical Safety: Other: Physeal Development under Actions).
USE IN THE ELDERLY: Refer to General: Arterial Thromboembolism as previously mentioned.
