Drug Action
Ravulizumab is a recombinant monoclonal antibody that inhibits terminal complement activation at the C5 protein and thereby reduces haemolysis in paroxysmal nocturnal haemoglobinuria.
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Drug reference
Ravulizumab is a recombinant monoclonal antibody that inhibits terminal complement activation at the C5 protein and thereby reduces haemolysis in paroxysmal nocturnal haemoglobinuria.
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Paroxysmal nocturnal haemoglobinuria (under expert supervision) ▶BY INTRAVENOUS INFUSION ▶Adult (body-weight 40–59 kg): Loading dose 2.4 g for 1 dose, infused over at least 114 minutes, then maintenance 3 g every 8 weeks, infused over at least 140 minutes. Start maintenance dosing 2 weeks after the loading dose, a maintenance dose (except for the first maintenance dose) may be given up to 7 days before or after the scheduled date; the subsequent dose should be given according to the original schedule ▶Adult (body-weight 60–99 kg): Loading dose 2.7 g for 1 dose, infused over at least 102 minutes, then maintenance 3.3 g every 8 weeks, infused over at least 120 minutes. Start maintenance dosing 2 weeks after the loading dose, a maintenance dose (except for the first maintenance dose) may be given up to 7 days before or after the scheduled date; the subsequent dose should be given according to the original schedule ▶Adult (body-weight 100 kg and above): Loading dose 3 g for 1 dose, infused over at least 108 minutes, then maintenance 3.6 g every 8 weeks, infused over at least 132 minutes. Start maintenance dosing 2 weeks after the loading dose, a maintenance dose (except for the first maintenance dose) may be given up to 7 days before or after the scheduled date; the subsequent dose should be given according to the original schedule DOSE EQUIVALENCE AND CONVERSION ▶For patients switching from eculizumab to ravulizumab, the initial loading dose of ravulizumab should be administered 2 weeks after the last eculizumab infusion.
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Patients unvaccinated against Neisseria meningitidis. unresolved Neisseria meningitidis infection Disturbances in utilisation of iron. iron overload
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Active systemic infection CAUTIONS, FURTHER INFORMATION ▶Meningococcal infection Manufacturer advises vaccinate against Neisseria meningitidis at least 2 weeks before treatment (vaccines against serotypes A, C, Y, W135 and B where available, are recommended); revaccinate according to current medical guidelines. Patients receiving ravulizumab less than 2 weeks after receiving meningococcal vaccine must be given prophylactic antibiotics until 2 weeks after vaccination. Advise patient to report promptly any signs of meningococcal infection. Other immunisations should also be up to date. Allergic disorders. eczema. hepatic dysfunction. immune conditions. infection (discontinue if ongoing bacteraemia). inflammatory conditions. oral iron should not be given until 5 days after the last injection. severe asthma
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Ravulizumab is a biological medicine. Biological medicines must be prescribed and dispensed by brand name, see Biological medicines and Biosimilar medicines, under Guidance on prescribing p. 1. The manufacturer of Ultomiris ® has provided a Physician’s guide for healthcare professionals. l HANDLING AND STORAGE Store in a refrigerator (2-8°C) and protect from light—consult product literature for further information regarding storage outside refrigerator.
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▶Common or very common Arthralgia. asthenia. back pain. chills. diarrhoea. dizziness. fever. gastrointestinal discomfort. headache. increased risk of infection. influenza like illness. meningococcal sepsis. muscle complaints. nausea. skin reactions. vomiting ▶Frequency not known Infusion related reaction ▶Common or very common Dizziness. flushing. headache. hypertension. hypophosphataemia. hypotension. nausea . skin reactions. taste altered ▶Uncommon Arrhythmias. arthralgia. bronchospasm. chest pain. chills. constipation. diarrhoea. dyspnoea. fatigue. fever. gastrointestinal discomfort. hyperhidrosis. hypersensitivity. loss of consciousness. muscle complaints. pain. peripheral oedema. sensation abnormal . vision blurred. vomiting ▶Rare or very rare Angioedema. anxiety. circulatory collapse. influenza like illness. malaise. pallor. palpitations. psychiatric disorder. seizure. syncope. tremor ▶Frequency not known Kounis syndrome SIDE-EFFECTS, FURTHER INFORMATION Anaphylactic reactions can occur with parenteral administration of iron complexes and facilities for cardiopulmonary resuscitation must be available. Overdose For details on the management of poisoning, see Iron salts, under Emergency treatment of poisoning p. 1430. eiiii F 1079
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Manufacturer advises effective contraception during and for up to 8 months after treatment.
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Manufacturer advises use only if potential benefit outweighs risk—no information available. Ravulizumab is an immunoglobulin G (IgG) monoclonal antibody; human IgG antibodies are known to cross the placenta.
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Manufacturer advises avoid breast- feeding during and for up to 8 months after treatment—no information available.
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Manufacturer advises monitor for intravascular haemolysis (including serum- lactate dehydrogenase concentration) for at least 16 weeks after stopping treatment; consider restarting ravulizumab if haemolysis occurs.
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MHRA/CHM ADVICE: SERIOUS HYPERSENSITIVITY REACTIONS WITH INTRAVENOUS IRON (AUGUST 2013) Serious hypersensitivity reactions, including life- threatening and fatal anaphylactic reactions, have been reported in patients receiving intravenous iron. These reactions can occur even when a previous administration has been tolerated (including a negative test dose). Test doses are no longer recommended and caution is needed with every dose of intravenous iron. Intravenous iron products should only be administered when appropriately trained staff and resuscitation facilities are immediately available; patients should be closely monitored for signs of hypersensitivity during and for at least 30 minutes after every administration. In the event of a hypersensitivity reaction, treatment should be stopped immediately and appropriate management initiated. The risk of hypersensitivity is increased in patients with known allergies, immune or inflammatory conditions, or those with a history of severe asthma, eczema, or other atopic allergy; in these patients, intravenous iron should only be used if the benefits outweigh the risks. Blood and nutrition Intravenous iron should be avoided in the first trimester of pregnancy and used in the second or third trimesters only if the benefit outweighs the potential risks for both mother and fetus.
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Manufacturer advises for intravenous infusion (Ultomiris ®), give intermittently in Sodium Chloride 0.9%. Dilute requisite dose with infusion fluid to a final concentration of 5 mg/mL and administer through an in-line filter (0.2 micron).
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There can be variation in the licensing of different medicines containing the same drug. Solution for infusion EXCIPIENTS: May contain Polysorbates ELECTROLYTES: May contain Sodium A ▶Ultomiris (Alexion Pharma UK Ltd) Ravulizumab 10 mg per 1 ml Ultomiris 300mg/30ml concentrate for solution for infusion vials | 1 vial P s (Hospital only) 1.2 Iron deficiency anaemia Anaemia, iron deficiency Iron deficiency, treatment and prophylaxis Treatment with an iron preparation is justified only in the presence of a demonstrable iron-deficiency state. Before starting treatment, it is important to exclude any serious underlying cause of the anaemia (e.g. gastric erosion, gastro- intestinal cancer). Prophylaxis with an iron preparation may be appropriate in malabsorption, menorrhagia, pregnancy, after subtotal or total gastrectomy, in haemodialysis patients, and in the management of low birth-weight infants such as preterm neonates. Oral iron Iron salts should be given by mouth unless there are good reasons for using another route. Ferrous salts show only marginal differences between one another in efficiency of absorption of iron. Haemoglobin regeneration rate is little affected by the type of salt used provided sufficient iron is given, and in most patients the speed of response is not critical. Choice of preparation is thus usually decided by the incidence of side-effects and cost. The oral dose of elemental iron for iron-deficiency anaemia should be 100 to 200 mg daily. It is customary to give this as dried ferrous sulfate; for prophylaxis of iron- deficiency anaemia, ferrous sulfate may be effective. Iron content of different iron salts Iron salt/amount Content of ferrous iron ferrous fumarate 200 mg 65 mg ferrous gluconate 300 mg 35 mg ferrous sulfate 300 mg 60 mg ferrous sulfate, dried 200 mg 65 mg Compound preparations Preparations containing iron and folic acid p. 1084 are used during pregnancy in women who are at high risk of developing iron and folic acid deficiency; they should be distinguished from those used for the prevention of neural Blood and nutrition tube defects in women planning a pregnancy. It is important to note that the small doses of folic acid contained in these preparations are inadequate for the treatment of megaloblastic anaemias. Some oral preparations contain ascorbic acid p. 1143 to aid absorption of the iron but the therapeutic advantage of such preparations is minimal and cost may be increased. There is no justification for the inclusion of other ingredients, such as the B group of vitamins (except folic acid for pregnant women). Modified-release preparations Modified-release preparations of iron are licensed for once- daily dosage, but have no therapeutic advantage and should not be used. These preparations are formulated to release iron gradually; the low incidence of side-effects may reflect the small amounts of iron available for absorption as the iron is carried past the first part of the duodenum into an area of the gut where absorption may be poor. Parenteral iron Iron can be administered parenterally as iron dextran p. 1080, iron sucrose p. 1081, ferric carboxymaltose p. 1080, or iron isomaltoside 1000 p. 1080. Parenteral iron is generally reserved for use when oral therapy is unsuccessful because the patient cannot tolerate oral iron, or does not take it reliably, or if there is continuing blood loss, or in malabsorption. Parenteral iron may also have a role in the management of chemotherapy-induced anaemia, when given with erythropoietins, in specific patient groups (see NICE guidance). Many patients with chronic renal failure who are receiving haemodialysis (and some who are receiving peritoneal dialysis) also require iron by the intravenous route on a regular basis. With the exception of patients with severe renal failure receiving haemodialysis, parenteral iron does not produce a faster haemoglobin response than oral iron provided that the oral iron preparation is taken reliably and is absorbed adequately. Depending on the preparation used, parenteral iron is given as a total dose or in divided doses. Further treatment should be guided by monitoring haemoglobin and serum iron concentrations. MINERALS AND TRACE ELEMENTS › IRON, INJECTABLE Iron (injectable) f
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Patients or carers should be advised to report promptly any signs of meningococcal infection. Advice about prevention of gonorrhoea should also be given. A patient information card and a patient safety card should be provided.
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Loading dose 2.4 g for
First-line fragment. Read the complete Indications and Dose section above.
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Loading dose 2.7 g for
First-line fragment. Read the complete Indications and Dose section above.
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Loading dose 3 g
First-line fragment. Read the complete Indications and Dose section above.
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