HCP section – Avastin Roche Abbreviated Prescribing Information
Avastin Roche Injection 100 mg/4 ml (bevacizumab)
Indications: Metastatic colorectal cancer (mCRC) – in combination with fluoropyrimidine-based chemotherapy. Metastatic breast cancer (mBC) – in combination with paclitaxel for 1st line mBC. Non-small cell lung cancer (NSCLC) – in addition to platinum-based chemotherapy for 1st line treatment of unresectable, advanced, metastatic or recurrent NSCLC other than predominantly squamous cell histology; in combination with erlotinib, is indicated for first-line treatment of adult patients with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) activating mutations. Advanced and/or metastatic renal cell carcinoma (mRCC) – in combination with interferon alfa-2a. Glioblastoma – for the treatment of glioblastoma with progressive disease following prior therapy as a single agent. Epithelial ovarian, fallopian tube or primary peritoneal cancer – in combination with carboplatin and paclitaxel for front-line treatment of advanced (FIGO stage III B, III C & IV) cancer; in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel for 1st recurrence of platinum-sensitive cancer who have not received prior bevacizumab therapy/other VEGF inhibitors / receptor-targeted agents; in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin is indicated for the treatment of adult patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. Cervical Cancer – in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in patients who cannot receive platinum therapy, is indicated for the treatment of adult patients with persistent, recurrent, or metastatic carcinoma of the cervix.
Dosage & Administration: Physicians experienced in antineoplastic medicines should supervise Avastin Roche administration. Continue treatment until progression of underlying disease or unacceptable toxicity (except for Glioblastoma). mCRC – 5mg/kg or 10mg/kg every 2 weeks; or 7.5mg/kg or 15mg/kg Q3wks. mBC – 10mg/kg Q2 wks; or 15mg/kg Q3 wks. NSCLC (First-line treatment of non-squamous NSCLC in combination with platinum-based chemotherapy) – 7.5mg/kg or 15mg/kg Q3wks in addition to platinum-based chemotherapy for up to 6 cycles, then as monotherapy. mRCC/Glioblastoma – 10mg/kg once Q2wks; NSCLC (First-line treatment of non-squamous NSCLC with EGFR activating mutations in combination with erlotinib) – 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion in addition to erlotinib. Epithelial ovarian/Fallopian tube/Primary peritoneal cancer – front-line: 15mg/kg once Q3wks in addition to carboplatin and paclitaxel for up to 6 cycles, then as monotherapy; platinum-sensitive recurrent disease: 15mg/kg once Q3wks in combination with either carboplatin and gemcitabine for 6 cycles and up to 10 cycles or in combination with carboplatin and paclitaxel for 6 cycles and up to 8 cycles, then as monotherapy; platinum-resistant recurrent disease: 10mg/kg once every 2 weeks in combination with paclitaxel or pegylated liposomal doxorubicin or 15mg/kg with topotecan (given on days 1-5, every 3 weeks) once every 3 weeks. Cervical cancer – 15mg/kg once every 3 weeks in combination with one of the following regime: paclitaxel and cisplatin or paclitaxel and topotecan. Method of administration: initial dose: IV infusion over 90 mins; if well tolerated, second dose: IV infusion over 60 mins; if well tolerated, subsequent doses: IV infusion over 30 mins. Do not administer as IV push or bolus or mix with glucose. Dose reduction for adverse events not recommended. If indicated, discontinue or temporarily suspend therapy. No recommendations for use in children (<18 years old). No dose adjustment in the elderly.
Contraindications: Hypersensitivity to bevacizumab or any of the excipients, Chinese hamster ovary cell products and other recombinant human or humanised antibodies. Pregnancy.
Warnings & Precautions: Trade name of administered product should be clearly recorded to improve traceability. Gastrointestinal (GI) perforation: increased risk for development of GI and gall bladder perforation; intra-abdominal inflammatory process may be a risk factor in patients with metastatic carcinoma of the colon or rectum; discontinue therapy permanently in patients who develop GI perforation. Fistulae: permanently discontinue in tracheoesophageal or any Grade 4 fistula, consider discontinuation in non-GI fistula. Patients treated for persistent, recurrent, or metastatic cervical cancer are at increased risk of fistulae between the vagina and any part of the GI tract. Wound healing: do not initiate for at least 28 days following major surgery or until surgical wound is fully healed; withhold for elective surgery. Necrotizing Fasciitis: cases including fatality have been reported, discontinue therapy and initiate appropriate treatment. Hypertension: control pre-existing hypertension prior to treatment. Monitor blood pressure during therapy and control hypertension with standard antihypertensive therapy; the use of diuretics is not advised in patients on cisplatin-based chemotherapy. Permanently discontinue if hypertension remains uncontrolled or for hypertensive crisis/encephalopathy. Posterior Reversible Encephalopathy Syndrome (PRES): signs include: seizures, headache, altered mental status, visual disturbance or cortical blindness with/without associated hypertension. Confirm by brain imaging, treat symptoms and discontinue Avastin Roche once developed. Proteinuria: Patients with a history of hypertension may be at increased risk; monitoring of proteinuria by dipstick urinalysis is recommended prior to and during therapy. Permanently discontinue therapy if Grade 4 proteinuria develops. Arterial thromboembolism: including cerebrovascular accidents, transient ischaemic attacks and myocardial infarctions, especially if with prior history, diabetes or in elderly. Permanently discontinue therapy if arterial thromboembolic events develop. Venous thromboembolism: including pulmonary embolism; discontinue in Grade 4 pulmonary embolism and closely monitor where ≤Grade 3. Patients treated for persistent, recurrent, or metastatic cervical cancer in combination with paclitaxel and cisplatin may be at increased risk of venous thromboembolic events. Haemorrhage, especially tumour-associated haemorrhage: discontinue permanently if Grade 3/4. Risk of CNS haemorrhage in patients with untreated CNS metastases has not been prospectively evaluated. Monitor for signs and symptoms of CNS bleeding and discontinue Avastin Roche in cases of intracranial bleeding. Caution in patients with congenital bleeding diathesis, acquired coagulopathy or during anticoagulant therapy. Serious/fatal pulmonary haemorrhage/haemoptysis in NSCLC: do not use where recent significant pulmonary haemorrhage/haemoptysis (>1/2 teaspoon of red blood). Aneurysms and artery dissections: The use of VEGF pathway inhibitors in patients with or without hypertension may promote the formation of aneurysms and/or artery dissections, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm Congestive Heart Failure (CHF): caution in patients with clinically significant cardiovascular disease or pre-existing CHF; 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. Neutropenia and infections: fatal infection with or without severe neutropenia in combination with myelotoxic chemotherapy, mainly seen in platinum- or taxane-based therapies for NSCLC and mBC. Hypersensitivity: Close observation during and following drug administration. Infusion should be discontinued and appropriate medical therapies should be administered if a reaction occurs. Osteonecrosis of the jaw (ONJ): concomitant treatment with i.v. bisphosphonates and invasive dental procedures are identified risk factors to ONJ; patients who have previously received or are receiving i.v. bisphosphonates should avoid invasive dental procedures. Intravitreal use: Avastin Roche is not formulated for intravitreal use. Eye disorders: including endophthalmitis, intraocular inflammation, retinal detachment, retinal pigment epithelial tear, intraocular pressure increased and intraocular haemorrhage have been reported following unapproved intravitreal use of Avastin Roche compounded from vials approved for cancer patients, some reactions results in visual loss. Systemic effect following intravitreal use: reduction of VEGF conc. has been demonstrated, non-ocular haemorrhages and ATE has been reported. Ovarian Failure / Fertility: Fertility preservation strategies should be discussed with women of child-bearing potential prior to treatment.
Drug Interactions: No clinically relevant pharmacokinetic interaction between co-administered chemotherapy and Avastin Roche. Safety and efficacy with concomitant radiotherapy has not been established. Microangiopathic haemolytic anaemia has been reported when Avastin Roche was used with sunitinib malate; hypertension, elevated creatinine and neurological symptoms were also observed. Increased rates of severe neutropenia, febrile neutropenia, or infection with or without severe neutropenia have been observed in patients on platinum- or taxane-based therapies in the treatment of NSCLC and mBC. No interaction studies have been performed between EGFR monoclonal antibody and bevacizumab chemotherapy regimens, decreased PFS/OS and increased toxicity was observed in phase III studies. Use in Pregnancy & Lactation: Avastin Roche should not be used during pregnancy because no adequate & well-controlled data. Inhibition of foetal angiogenesis is anticipated. Avastin Roche may have temporary adverse effect on female fertility and cause ovarian failure. Women with childbearing potential must use effective contraception during and for up to 6 months after treatment. Discontinue breast-feeding during treatment and for at least 6 months after last dose.
Undesirable Effects: For full listings please refer to the Avastin Roche package insert. Most serious reactions: GI perforation; haemorrhage including pulmonary haemorrhage/haemoptysis and arterial thromboembolism. Serious reactions, very common: Febrile neutropenia, leucopenia, thrombocytopenia, neutropenia, peripheral sensory neuropathy, hypertension, diarrhoea, nausea, vomiting, asthenia and fatigue. Serious reactions, common: Sepsis, abscess, infection, anaemia, hyponatremia, dehydration, cerebrovascular accident, syncope, somnolence, headache, congestive cardiac failure, supraventricular tachycardia, arterial thromboembolism, deep vein thrombosis, haemorrhage, pulmonary embolism, dyspnoea, hypoxia, epistaxis, intestinal perforation and obstruction, ileus, abdominal pain, GI disorder, stomatitis, palmar-plantar erythrodysaesthesia syndrome, muscular weakness, myalgia, arthralgia, proteinuria, urinary tract infection pain, lethargy and mucosal inflammation. All grades, very common: Anorexia, hypomagnesaemia, hyponatremia, dysgeusia, headache, dysarthria, eye disorder, lacrimation increased, hypertension, dyspnoea, epistaxis, cough, rhinitis. constipation, stomatitis, rectal haemorrhage, diarrhoea, ovarian failure, exfoliative dermatitis, dry skin, skin discolouration, arthralgia, myalgia, proteinuria, pyrexia, asthenia, pain and mucosal inflammation. Other reactions: Hypertensive encephalopathy. PRES (rare). Renal thrombotic Microangiopathy manifested as proteinuria. Nasal septum perforation. Pulmonary hypertension. Dysphonia. GI ulcer. Gall bladder perforation. Hypersensitivity. Necrotizing fasciitis. ONJ, Non-mandibular osteonecrosis. Laboratory abnormalities and Post Marketing – refer to package insert.
Date of Preparation: December 2021
Full prescribing information should be viewed prior to prescribing.
