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Aflibercept parenteral

Updated 2 Feb 2023 | Aflibercept


Infusions containing aflibercept

These products have been produced by recombinant technology using Chinese Hamster Ovary (CHO) cell lines.

Drugs List

  • aflibercept 100mg/4ml concentrate for solution for infusion
  • aflibercept 200mg/8ml concentrate for solution for infusion
  • ZALTRAP 100mg/4ml concentrate for solution for infusion
  • ZALTRAP 200mg/8ml concentrate for solution for infusion
  • Therapeutic Indications


    Treatment of advanced colorectal cancer combined with other cytotoxics

    To be used in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) chemotherapy in adults with metastatic colorectal cancer (mCRC) that is resistant to or has progressed after an oxaliplatin-containing regimen.


    Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.


    The recommended dose is 4 mg/kg of body weight. Followed by the FOLFIRI regimen.

    The treatment cycle is repeated every 2 weeks. Aflibercept treatment should be continued until disease progression or unacceptable toxicity occurs.

    Additional Dosage Information

    Recurrent febrile neutropenia or neutropenic sepsis
    Following dose reductions of the FOLFIRI products, a reduction of aflibercept to 2 mg/kg could be considered.

    Recurrent severe hypertension
    Suspend treatment until hypertension is controlled and reduce dose to 2 mg/kg for subsequent cycles.

    Proteinuria equal to or greater than 2 grams per 24 hours
    Suspend treatment until proteinuria is less than 2 grams per 24 hours.
    If proteinuria recurs treatment should be suspended until it drops below 2 grams per 24 hours and reduce to 2 mg/kg.


    Following dilution, to be administered as a slow intravenous infusion over 1 hour.


    Children under 18 years
    Severe haemorrhage
    New York Heart Association class III failure
    New York Heart Association class IV failure
    Uncontrolled hypertension

    Precautions and Warnings

    Performance status of ECOG greater than or equal to 2
    Tobacco smoking
    Within 4 weeks of surgery
    Behcet's disease
    Cerebrovascular disorder
    Diabetes mellitus
    Giant cell arteritis
    History of aneurysm
    History of severe cardiac disorder
    Ischaemic heart disease
    Marfan syndrome
    Occlusive peripheral arterial disease
    Severe hepatic impairment
    Severe renal impairment
    Takayasu arteritis
    Vascular Ehlers-Danlos syndrome

    Anti-diarrhoeals may be required during treatment
    Consider a dental exam & appropriate preventive dentistry before treatment
    Consider premedication with antihistamine and/or corticosteroid
    Ensure hypertension is controlled prior to treatment
    Prophylactic G-CSF should be considered
    Treatment to be initiated and supervised by a specialist
    Concentrate must be diluted and used as an infusion
    Consult local policy on the safe use of anti-cancer drugs
    Do not start therapy for 28 days post surgery, or until wound has healed
    For intravenous use only
    Interrupt treatment if infusion reaction occurs & monitor until resolution
    Staff: Not to be handled by pregnant staff
    Measurement of LV ejection fraction recommended before and during treatment
    Perform full blood count before each treatment cycle
    Monitor blood pressure every 2 weeks
    Monitor for bleeding during treatment
    Monitor for protein in urine
    Monitor for symptoms of gastrointestinal perforation or fistula
    Monitor patients for signs and symptoms of cardiac failure
    Advise patient to report headaches, seizures, confusion, visual disturbance
    Elderly patients may be more susceptible to local and systemic effects
    Discontinue 4 weeks prior to major elective surgery
    Discontinue at first signs of thrombotic microangiopathy
    Discontinue at the first signs of cardiac failure
    Discontinue if arterial thromboembolism develops
    Discontinue if fistulae develop during treatment
    Discontinue if grade 4 thromboembolic event occurs
    Discontinue if hypertensive encephalopathy occurs
    Discontinue if nephrotic syndrome occurs
    Discontinue if persistent hypertension unresponsive to therapy occurs
    Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
    Discontinue if severe haemorrhage occurs
    Discontinue if severe hypersensitivity reactions occur
    Discontinue permanently if hypertensive crisis occurs
    Discontinue treatment if gastrointestinal perforation occurs
    Suspend therapy if platelet count falls below 75,000 per cubic mm
    Suspend treatment if hypertension cannot be controlled
    Suspend treatment if neutrophil count is less than 1,500/cubic mm
    Suspend treatment if proteinuria greater than or equal to 2g/ 24 hours
    Discontinue if wound healing requires medical intervention
    May cause impaired fertility
    Male & female: Contraception required during & for 6 months after treatment
    Advise patient on giving up smoking
    Advise patient to report any dental mobility, pain or swelling

    Posterior Reversible Encephalopathy Syndrome (PRES)
    Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with aflibercept. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed aflibercept treatment should be discontinued and adequate blood pressure and seizure control administration is advisable.The safety of reinstating treatment in patients previously experiencing PRES is unknown.

    Patients with grade 3 deep vein thrombosis (DVT) should be treated with appropriate anticoagulation and continue treatment with aflibercept. However, if grade 3 DVT recurs despite anticoagulation treatment, aflibercept should be discontinued. Patients with thromboembolic events grade 3 or lower need to be closely monitored.

    Risk factors for aneurysm and artery dissection
    Use of systemic VEGF inhibitors may promote the formation of aneurysms or artery dissections, mainly in relation to aortic aneurysm rupture and aortic dissection. It is therefore important to consider the risk of aneurysm and artery dissection in patients with risk factors such as hypertension, history of aneurysm, smoking, diabetes, coronary, cerebrovascular or peripheral arterial disease, and hyperlipidaemia. Other risk factors include Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, and the use of fluoroquinolones. In patients receiving VEGF inhibitors, any modifiable risk factors such as smoking and hypertension should be reduced as far as possible.

    Pregnancy and Lactation


    Aflibercept is contraindicated in pregnancy.

    Animal studies have shown reproductive toxicity. Angiogenesis which is critical to foetal development, is inhibited by aflibercept and this may result in adverse effects on the pregnancy.

    If an inadvertent pregnancy occurs, the woman should be advised of the possible risk for severe adverse effects in the embryo and foetus.

    The effect of concurrent therapies must also be considered.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    Aflibercept is contraindicated in breastfeeding.

    It is unknown whether aflibercept is excreted in human milk, therefore a risk to breastfed infants cannot be excluded.

    The effect of concurrent therapies must also be considered.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at

    Side Effects

    Abdominal pain
    Aphthous stomatitis
    Cardiac failure
    Decreased appetite
    Decreased ejection fraction
    Febrile neutropenia
    Gastro-intestinal perforation
    Hyperpigmentation of skin
    Hypersensitivity reactions
    Increase in serum ALT/AST
    Nephrotic syndrome
    Oropharyngeal pain
    Osteonecrosis (primarily of the jaw)
    Palmar-Plantar Erythrodysaesthesia syndrome
    Posterior reversible encephalopathy syndrome (PRES)
    Rectal haemorrhage
    Serum creatinine increased
    Thromboembolic disorders
    Thrombotic microangiopathy
    Tooth ache
    Upper abdominal pain
    Urinary tract infections
    Weight loss
    Wound healing retarded


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: March 2016

    Reference Sources Government departments. Medicines and Healthcare products Regulatory Agency. Drug Safety Updates. Aflibercept (Zaltrap): Minimising the risk of osteonecrosis of the jaw. Available at: Last accessed: 22 April 2016

    Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 29 February 2016.

    MHRA Drug Safety Update July 2020
    Available at:
    Last accessed: 10 November 2020

    Summary of Product Characteristics: Zaltrap 25mg/ml concentrate for solution for infusion. Sanofi. Revised October 2016.

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