Drug reference
Aflibercept is a recombinant fusion protein that acts as a soluble decoy receptor and binds to vascular endothelial growth factors A and B (VEGF-A, VEGF-B) and placental growth factor (PlGF). Aflibercept inhibits 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.
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In combination with irinotecan, fluorouracil and folinic acid (FOLFIRI) chemotherapy, in metastatic colorectal cancer that is resistant to, or has progressed after, an oxaliplatin-containing regimen ▶BY INTRAVENOUS INFUSION ▶Adult: (consult local protocol)
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Moderate or severe congestive heart failure. uncontrolled hypertension
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Febrile neutropenia. history of cardiovascular disease (may be exacerbated by hypertension). increased risk of haemorrhage (including fatal events). increased risk of hypertension. increased risk of thromboembolic events (consult product literature if event occurs). may impair wound healing—withhold treatment for at least 4 weeks before elective surgery and for at least 4 weeks after major surgery, or until wound fully healed. neutropenic infection. risk of fistula formation (discontinue if fistula develops). risk of neutropenia. risk of thrombocytopenia
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NICE decisions ▶Aflibercept in combination with irinotecan and fluorouracil- based therapy for treating metastatic colorectal cancer that has progressed following prior oxaliplatin-based chemotherapy (March 2014) NICE TA307 Aflibercept in combination with irinotecan and fluorouracil-based therapy is not recommended within its marketing authorisation for treating metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing regimen. www.nice.org.uk/guidance/ta307 Immune system and malignant disease
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→Appendix 1: aflibercept Immune system and malignant disease
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▶Common or very common Appetite decreased. asthenic conditions. dehydration. diarrhoea. dysphonia. dyspnoea . embolism and thrombosis. fistula. gastrointestinal discomfort. gastrointestinal disorders. haemorrhage. headache. hypersensitivity. hypertension. increased risk of infection. leucopenia. neutropenia. neutropenic sepsis . oral disorders. oropharyngeal pain. proteinuria. rhinorrhoea. skin reactions. thrombocytopenia. weight decreased ▶Uncommon Healing impaired. heart failure. nephrotic syndrome. osteonecrosis of jaw. posterior reversible encephalopathy syndrome (PRES). thrombotic microangiopathy ▶Frequency not known Alopecia. anaemia. aneurysm. angina pectoris. artery dissection. cerebrovascular insufficiency. constipation. hyperbilirubinaemia. myocardial infarction. nausea. vomiting. wound complications
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Exclude pregnancy before treatment. Effective contraception required during and for at least 6 months after treatment in men and women. Contraceptive advice should be given to men and women before therapy begins (and should cover the duration of contraception required after therapy has ended).
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Manufacturer advises avoid—toxicity in animal studies. Considerable caution is necessary if a pregnant woman presents with cancer requiring chemotherapy, and specialist advice should always be sought.
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Manufacturer advises avoid—no information available.
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Manufacturer advises caution in severe impairment (no information available).
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Caution in severe impairment— no information available.
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▶Monitor blood pressure at initiation and at least fortnightly during treatment (do not initiate treatment if pre-existing hypertension is uncontrolled)—consult product literature if hypertension develops during treatment. ▶Monitor for signs of gastro-intestinal perforation (discontinue if perforation develops). ▶Monitor full blood count, including differential count and platelets at baseline and before each treatment cycle. ▶Monitor for proteinuria before each treatment administration (consult product literature if symptoms develop). ▶Monitor for signs and symptoms of diarrhoea and dehydration, particularly in elderly—consult product literature if severe diarrhoea occurs. ▶Monitor for posterior reversible encephalopathy syndrome (presenting as seizures, altered mental status, nausea, vomiting, headache, or visual disturbance).
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There can be variation in the licensing of different medicines containing the same drug. Solution for infusion ▶Zaltrap (Sanofi) Aflibercept 25 mg per 1 ml Zaltrap 200mg/8ml concentrate for solution for infusion vials | 1 vial P £591.30 (Hospital only) Zaltrap 100mg/4ml concentrate for solution for infusion vials | 1 vial P £295.65 (Hospital only) Chapter 9 Blood and nutrition CONTENTS Blood and blood-forming organs page 1069 Anaemias Hypoplastic, haemolytic, and renal anaemias 1.1 1.1a Atypical haemolytic uraemic syndrome and paroxysmal nocturnal haemoglobinuria Iron deficiency anaemia 1.2 Megaloblastic anaemia 1.3 Iron overload Neutropenia and stem cell mobilisation Neutropenia 3.1 Stem cell mobilisation 3.2 Platelet disorders Essential thrombocythaemia 4.1 Thrombocytopenias 4.2 4.2a Acquired thrombotic thrombocytopenic purpura 4.2b Immune thrombocytopenia Nutrition and metabolic disorders Fluid and electrolyte imbalances Calcium imbalance 1.1 1.1a Hypercalcaemia and hypercalciuria 1.1b Hypocalcaemia Low blood volume 1.2 Magnesium imbalance 1.3 1.3a Hypomagnesaemia Phosphate imbalance 1.4 1.4a Hyperphosphataemia 1.4b Hypophosphataemia Blood and blood-forming organs Anaemias Anaemias Anaemia treatment considerations Before initiating treatment for anaemia it is essential to determine which type is present. Iron salts may be harmful and result in iron overload if given alone to patients with anaemias other than those due to iron deficiency. Sickle-cell anaemia Sickle-cell disease is caused by a structural abnormality of haemoglobin resulting in deformed, less flexible red blood cells. Acute complications in the more severe forms include sickle-cell crisis, where infarction of the microvasculature and blood supply to organs results in severe pain. Sickle-cell crisis requires hospitalisation, intravenous fluids, analgesia and treatment of any concurrent infection. Chronic complications include skin ulceration, renal failure, and Potassium imbalance page 1117 1.5 1.5a Hyperkalaemia 1.5b Hypokalaemia Blood and nutrition Metabolic disorders Acute porphyrias 2.1 Carnitine deficiency 2.2 Cystinosis 2.3 2.3a Nephropathic cystinosis Fabry’s disease 2.4 Gaucher’s disease 2.5 Homocystinuria 2.6 Hypophosphatasia 2.7 Mucopolysaccharidosis 2.8 Niemann-pick type c disease 2.9 Pompe disease 2.10 Tyrosinaemia type i 2.11 Urea cycle disorders 2.12 Wilson’s disease 2.13 Mineral and trace elements deficiencies Selenium deficiency 3.1 Zinc deficiency 3.2 Nutrition (intravenous) Nutrition (oral) Special diets 5.1 5.1a Phenylketonuria Vitamin deficiency Neural tube defects (prevention in pregnancy) 6.1 increased susceptibility to infection. Pneumococcal vaccine, haemophilus influenzae type b vaccine, an annual influenza vaccine and prophylactic penicillin reduce the risk of infection. Hepatitis B vaccine should be considered if the patient is not immune. In most forms of sickle-cell disease, varying degrees of haemolytic anaemia are present accompanied by increased erythropoiesis; this may increase folate requirements and folate supplementation may be necessary. Hydroxycarbamide p. 985 can reduce the frequency of crises and the need for blood transfusions in sickle-cell disease. The beneficial effects of hydroxycarbamide may not become evident for several months. G6PD deficiency Glucose 6-phosphate dehydrogenase (G6PD) deficiency is highly prevalent in individuals originating from most parts of Africa, from most parts of Asia, from Oceania, and from Southern Europe; it can also occur, rarely, in any other individuals. G6PD deficiency is more common in males than it is in females. Individuals with G6PD deficiency are susceptible to developing acute haemolytic anaemia when they take a number of common drugs. They are also susceptible to developing acute haemolytic anaemia when they eat fava beans (broad beans, Vicia faba); this is termed favism and can be more severe in children or when the fresh fava beans are eaten raw. When prescribing drugs for patients with G6PD deficiency, the following three points should be kept in mind: . G6PD deficiency is genetically heterogeneous; susceptibility to the haemolytic risk from drugs varies; thus, a drug found to be safe in some G6PD-deficient individuals may not be equally safe in others; . manufacturers do not routinely test drugs for their effects in G6PD-deficient individuals; . the risk and severity of haemolysis is almost always dose- related. The lists below should be read with these points in mind. Ideally, information about G6PD deficiency should be Blood and nutrition available before prescribing a drug listed below. However, in the absence of this information, the possibility of haemolysis should be considered, especially if the patient belongs to a group in which G6PD deficiency is common. A very few G6PD-deficient individuals with chronic non- spherocytic haemolytic anaemia have haemolysis even in the absence of an exogenous trigger. These patients must be regarded as being at high risk of severe exacerbation of haemolysis following administration of any of the drugs listed below. Drugs with definite risk of haemolysis in most G6PD-deficient individuals . Dapsone and other sulfones (higher doses for dermatitis herpetiformis more likely to cause problems) . Fluoroquinolones (including ciprofloxacin, moxifloxacin, norfloxacin, and ofloxacin) . Methylthioninium chloride . Niridazole [not on UK market] . Nitrofurantoin . Pamaquin [not on UK market] . Primaquine (30 mg weekly for 8 weeks has been found to be without undue harmful effects in African and Asian people) . Quinolones (such as nalidixic acid [not on UK market]) . Rasburicase . Sulfonamides (including co-trimoxazole; some sulfonamides, e.g. sulfadiazine, have been tested and found not to be haemolytic in many G6PD-deficient individuals) Drugs with possible risk of haemolysis in some G6PD- deficient individuals . Aspirin (acceptable up to a dose of at least 1 g daily in most G6PD-deficient individuals) . Chloroquine (acceptable in acute malaria and malaria chemoprophylaxis) . Menadione, water-soluble derivatives (e.g. menadiol sodium phosphate) . Quinidine (acceptable in acute malaria) [not on UK market] . Quinine (acceptable in acute malaria) . Sulfonylureas Naphthalene in mothballs also causes haemolysis in individuals with G6PD deficiency. Hypoplastic, haemolytic, and renal anaemias Anabolic steroids, pyridoxine hydrochloride p. 1141, antilymphocyte immunoglobulin, rituximab p. 933 [unlicensed indication], and various corticosteroids are used in hypoplastic and haemolytic anaemias. Antilymphocyte immunoglobulin given intravenously through a central line over 12–18 hours each day for 5 days produces a response in about 50% of cases of acquired aplastic anaemia; the response rate may be increased when ciclosporin p. 883 is given as well. Severe reactions are common in the first 2 days and profound immunosuppression can occur; antilymphocyte immunoglobulin should be given under specialist supervision with appropriate resuscitation facilities. Alternatively, oxymetholone tablets (available from ‘special order’ manufacturers or specialist importing companies) can be used in aplastic anaemia for 3 to 6 months. It is unlikely that dietary deprivation of pyridoxine hydrochloride produces clinically relevant haematological effects. However, certain forms of sideroblastic anaemia respond to pharmacological doses, possibly reflecting its role as a co-enzyme during haemoglobin synthesis. Pyridoxine hydrochloride is indicated in both idiopathic acquired and hereditary sideroblastic anaemias. Although complete cures have not been reported, some increase in haemoglobin can occur; the dose required is usually high. Reversible sideroblastic anaemias respond to treatment of the underlying cause but in pregnancy, haemolytic anaemias, and alcohol dependence, or during isoniazid p. 621 treatment, pyridoxine hydrochloride is also indicated. Corticosteroids have an important place in the management of haematological disorders. They include conditions with an autoimmune haemolytic anaemia, immune thrombocytopenias and neutropenias, and major transfusion reactions. They are also used in chemotherapy schedules for many types of lymphoma, lymphoid leukaemias, and paraproteinaemias, including multiple myeloma. Erythropoietins Epoetins (recombinant human erythropoietins) are used to treat the anaemia associated with erythropoietin deficiency in chronic renal failure, to increase the yield of autologous blood in normal individuals and to shorten the period of symptomatic anaemia in patients receiving cytotoxic chemotherapy. Epoetin beta p. 1074 is also used for the prevention of anaemia in preterm neonates of low birth-weight; only unpreserved formulations should be used in neonates because other preparations may contain benzyl alcohol. Darbepoetin alfa p. 1071 is a hyperglycosylated derivative of epoetin; it has a longer half life and can be administered less frequently than epoetin. Methoxy polyethylene glycol-epoetin beta p. 1076 is a continuous erythropoietin receptor activator that is licensed for the treatment of symptomatic anaemia associated with chronic kidney disease. It has a longer duration of action than epoetin. Hypoplastic, haemolytic, and 1.1 renal anaemias Other drugs used for Hypoplastic, haemolytic, and renal anaemias Eltrombopag, p. 1094 ANABOLIC STEROIDS › ANDROSTAN DERIVATIVES
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(consult local protocol)
First-line fragment. Read the complete Indications and Dose section above.
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