Company: Sanofi-Aventis Ireland Ltd.
Legal category: Prescription. Hospital. Sport permitted.
Active ingredient: Aflibercept 100mg/4ml, 200mg/8ml.
Description: Concentrate for solution for infusion.
Presentation: Price available on request.
Indications: In combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) chemotherapy in adults with metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing regimen.
Pharmacology: Aflibercept is a recombinant fusion protein. It acts as a soluble decoy receptor that binds to VEGF-A. By acting as a ligand trap, it prevents binding of endogenous ligands to their cognate receptors and thereby blocks receptor mediated signaling. It blocks the activation of VEGF receptors and the proliferation of endothelial cells, thereby inhibiting the growth of new vessels that supply tumours with oxygen and nutrients.
Dosage: Adult: Treatment cycle: 4mg/kg body weight administered by intravenous infusion over 1 hour, followed by the FOLFIRI regimen (see SPC). Repeat cycle every 2 weeks. Continue until disease progression or unacceptable toxicity occurs. Elderly: As per adults. Children: No relevant use.
Contraindications: Hypersensitivity to the active ingredient or to any of the excipients. Ophthalmic/intravitreal use. Pregnancy (unless benefit outweighs risk). Female and male patients should use effective contraception during and up to a minimum of 6 months after the last dose of treatment.
Special precautions: Do not administer by intravenous push/bolus. Do not use in patients with severe haemorrhage (discontinue if occurs) or NYHA class III or IV congestive heart failure. Caution: Severe renal impairment, history of cardiovascular disease (such as coronary artery disease, or congestive heart failure), retreating patients with prior hypersensitivity reactions. Monitor complete blood count with differential at baseline, prior to initiation of each treatment cycle and as clinically necessary; delay treatment until platelet count ≥75 x 109/L and neutrophil count ≥1.5 x 109/L; modify dose if febrile neutropenia or neutropenic sepsis occur. Control hypertension before initiation; monitor blood pressure every two weeks (including before each administration or as clinically indicated) and regularly if hypertension develops; suspend treatment until controlled if recurrent (reduce dose for subsequent cycles); permanently discontinue if cannot be managed or if hypertensive crisis or hypertensive encephalopathy occurs. Monitor for worsening of proteinuria (or development of) before each administration; discontinue if nephrotic syndrome or thrombotic microangiopathy develops. Monitor for gastrointestinal (GI) perforation (discontinue if occurs). Carefully monitor for diarrhoea and dehydration (≥65 years); modify FOLFIRI regimen if severe (discontinue if persists). Carefully monitor patients with ECOG performance status ≥2 or with significant co-morbidities for early clinical deterioration. Increased risk of haemorrhage (including severe and sometimes fatal) reported; monitor for GI bleeding and other severe bleeding. Suspend treatment for at least 4 weeks prior to elective surgery; do not initiate until surgical wound is fully healed (for at least 4 weeks following major surgery); discontinue if healing requires medical intervention. Discontinue if fistula, arterial thromboembolic events or posterior reversible encephalopathy syndrome develops. Venous thromboembolic events reported; grade 4 including pulmonary embolism (discontinue); grade 3 DVT (discontinue if recurs despite anticoagulation treatment); ≤grade 3 (closely monitor). Hypersensitivity reactions may occur; mild to moderate (suspend until resolved); discontinue if severe (including bronchospasm, dyspnoea, angioedema, anaphylaxis). Modify dose if severe stomatitis and Palmar-Plantar Erythrodysaesthesia syndrome occur. See SPCs of FOLFIRI components. Likely to affect fertility during treatment. Driving/using machines (if vision or concentration affected). Lactation (assess risk/benefit).
Drug interactions: None known.
Adverse drug reactions: Infection, neutropenic infection/sepsis, urinary tract infection, nasopharyngitis, leucopenia, neutropenia (including febrile), thrombocytopenia, hypersensitivity, decreased appetite, weight loss, dehydration, headache, hypertension, haemorrhage, arterial thromboembolism, venous thromboembolism, dyspnoea, epistaxis, dysphonia, oropharyngeal pain, rhinorrhoea, gastrointestinal disorders, increased AST, increased ALT, Palmar-Plantar Erythrodysaesthesia syndrome, skin hyperpigmentation, proteinuria, increased serum creatinine, asthenic conditions.
Full prescribing information and references available from Sanofi-Aventis Ireland Ltd. Telephone: (01) 4035600. E-mail: IEmedinfo@sanofi.com.
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