Drug Action
Romiplostim is an Fc–peptide fusion protein that binds to and activates the thrombopoietin (TPO) receptor, thereby increasing platelet production.
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Drug reference
Romiplostim is an Fc–peptide fusion protein that binds to and activates the thrombopoietin (TPO) receptor, thereby increasing platelet production.
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Chronic immune (idiopathic) thrombocytopenic purpura in patients refractory to other treatments (such as corticosteroids or immunoglobulins) (under expert supervision) ▶BY SUBCUTANEOUS INJECTION ▶Adult: Initially 1 microgram/kg once weekly, adjusted in steps of 1 microgram/kg once weekly (max. per dose Blood and nutrition 10 micrograms/kg once weekly) until a stable platelet count of 50x109/litre or more is reached, consult product literature for further details of dose adjustments, discontinue treatment if inadequate response after 4 weeks at maximum dose
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Risk factors for thromboembolism
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NICE decisions ▶Romiplostim for the treatment of chronic immune (idiopathic) thrombocytopenic purpura (updated October 2018) NICE TA221 Romiplostim (Nplate ®) is recommended as an option for the treatment of chronic immune (idiopathic) thrombocytopenic purpura in adults, only if: . their condition is refractory to standard active treatments and rescue therapies, or . they have severe disease and a high risk of bleeding that needs frequent courses of rescue therapies. Romiplostim is recommended only if the manufacturer makes it available with the discount agreed in the patient Blood and nutrition access scheme. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta221 Scottish Medicines Consortium (SMC) decisions SMC No. 553/09 The Scottish Medicines Consortium has advised (October 2009) that romiplostim (Nplate ®) is accepted for restricted use within NHS Scotland for adult chronic immune (idiopathic) thrombocytopenic purpura (ITP) splenectomised patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins) and as second-line treatment for adult non-splenectomised patients where surgery is contra-indicated. Romiplostim is restricted to those with severe symptomatic ITP or those with a high risk of bleeding.
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▶Common or very common Anaemia. angioedema. arthralgia. asthenia. bone marrow disorders. chills. constipation. diarrhoea. dizziness. embolism and thrombosis. fever. flushing. gastrointestinal discomfort. headaches. hypersensitivity. increased risk of infection. influenza like illness. muscle complaints. nausea. pain. palpitations. peripheral oedema. sensation abnormal. skin reactions. sleep disorders ▶Uncommon Alopecia. appetite decreased. chest pain. clonus. cough. dehydration. depression. dry throat. dysphagia. dyspnoea. erythromelalgia. eye disorders. eye pruritus. feeling hot. feeling jittery. gastrooesophageal reflux disease. gout. haemorrhage. hair growth abnormal . hypotension. irritability. leucocytosis. malaise. muscle weakness. myocardial infarction. nasal complaints. neoplasms. oral disorders. papilloedema. peripheral ischaemia. peripheral neuropathy. photosensitivity reaction. pleuritic pain. portal vein thrombosis. skin nodule. splenomegaly. taste altered. thrombocytosis. tooth discolouration. vertigo. vision disorders. vomiting. weight changes
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Manufacturer advises avoid—toxicity in animal studies.
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Manufacturer advises avoid—no information available.
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Manufacturer advises caution; consider avoiding in moderate to severe impairment (risk of thromboembolic complications).
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Manufacturer advises caution—no information available.
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▶Manufacturer advises monitor full blood count and peripheral blood smears for morphological abnormalities before and during treatment. ▶Manufacturer advises monitor platelet count weekly until platelet count reaches 50x109/litre or more for at least 4 weeks without dose adjustment, then monthly thereafter. ▶Manufacturer advises monitor platelet count following treatment discontinuation—risk of bleeding.
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There can be variation in the licensing of different medicines containing the same drug. Powder and solvent for solution for injection ▶Nplate (Amgen Ltd) Romiplostim 250 microgram Nplate 250microgram powder and solvent for solution for injection pre-filled disposable devices | 1 pre- filled disposable injection P £482.00 Powder for solution for injection ▶Nplate (Amgen Ltd) Romiplostim 125 microgram Nplate 125microgram powder for solution for injection vials | 1 vial P £241.00 Nutrition and metabolic disorders Fluid and electrolyte imbalances Fluids and electrolytes Electrolyte replacement therapy The electrolyte concentrations (intravenous fluid) table and the electrolyte content (gastro-intestinal secretions) table may be helpful in planning replacement electrolyte therapy; faeces, vomit, or aspiration should be saved and analysed where possible if abnormal losses are suspected. Oral preparations for fluid and electrolyte imbalance Sodium and potassium salts, may be given by mouth to prevent deficiencies or to treat established deficiencies of mild or moderate degree. Oral potassium Compensation for potassium loss is especially necessary: . in those taking digoxin or anti-arrhythmic drugs, where potassium depletion may induce arrhythmias; . in patients in whom secondary hyperaldosteronism occurs, e.g. renal artery stenosis, cirrhosis of the liver, the nephrotic syndrome, and severe heart failure; . in patients with excessive losses of potassium in the faeces, e.g. chronic diarrhoea associated with intestinal malabsorption or laxative abuse. Measures to compensate for potassium loss may also be required in the elderly since they frequently take inadequate amounts of potassium in the diet (but see warning on renal insufficiency). Measures may also be required during long- term administration of drugs known to induce potassium loss (e.g. corticosteroids). Potassium supplements are seldom required with the small doses of diuretics given to treat hypertension; potassium-sparing diuretics (rather than potassium supplements) are recommended for prevention of hypokalaemia due to diuretics such as furosemide p. 241 or the thiazides when these are given to eliminate oedema. If potassium salts are used for the prevention of hypokalaemia, then doses of potassium chloride daily (in divided doses) by mouth are suitable in patients taking a normal diet. Smaller doses must be used if there is renal insufficiency (common in the elderly) to reduce the risk of hyperkalaemia. Potassium salts cause nausea and vomiting and poor compliance is a major limitation to their effectiveness; when appropriate, potassium-sparing diuretics are preferable. When there is established potassium depletion larger doses may be necessary, the quantity depending on the severity of any continuing potassium loss (monitoring of plasma- potassium concentration and specialist advice would be required). Potassium depletion is frequently associated with chloride depletion and with metabolic alkalosis, and these disorders require correction. Management of hyperkalaemia Acute severe hyperkalaemia (plasma-potassium concentration above 6.5 mmol/litre or in the presence of ECG changes) calls for urgent treatment with calcium gluconate 10% p. 1108 by slow intravenous injection, titrated and adjusted to ECG improvement, to temporarily protect against myocardial excitability. An intravenous injection of soluble insulin (5–10 units) with 50 mL glucose 50% p. 1102 given over 5- 15 minutes, reduces serum-potassium concentration; this is repeated if necessary or a continuous infusion instituted. Salbutamol p. 267 [unlicensed indication], by nebulisation or slow intravenous injection may also reduce plasma- potassium concentration; it should be used with caution in patients with cardiovascular disease. The correction of causal or compounding acidosis with sodium bicarbonate infusion p. 1099 should be considered (important: preparations of sodium bicarbonate and calcium salts should not be administered in the same line—risk of precipitation). Drugs exacerbating hyperkalaemia should be reviewed and stopped as appropriate; occasionally haemodialysis is needed. Ion-exchange resins may be used to remove excess potassium in mild hyperkalaemia or in moderate hyperkalaemia when there are no ECG changes. Oral sodium and water Sodium chloride p. 1101 is indicated in states of sodium depletion and usually needs to be given intravenously. In chronic conditions associated with mild or moderate degrees of sodium depletion, e.g. in salt-losing bowel or renal disease, oral supplements of sodium chloride or sodium bicarbonate, according to the acid-base status of the patient, may be sufficient. Fluids and electrolytes Electrolyte concentrations—intravenous fluids Na+ K+ Intravenous infusion 4.5 Normal plasma values Sodium Chloride 0.9% – Compound Sodium Lactate (Hartmann’s) Sodium Chloride 0.18% and Glucose 4% – (Adults only) Sodium Chloride 0.45% and Glucose 5% – (Children only) Potassium Chloride 0.15% and Glucose 5% – (Children only) Potassium Chloride 0.15% and Sodium Chloride 0.9% (Children only) Potassium Chloride 0.3% and Glucose 5% – Potassium Chloride 0.3% and Sodium Chloride 0.9% To correct metabolic acidosis Sodium Bicarbonate 1.26% – Sodium Bicarbonate 8.4% for cardiac arrest – Sodium Lactate (m/6) – Electrolyte content—gastro-intestinal secretions H+ Na+ Type of fluid 40–60 20–80 Gastric 120–140 – Biliary 120–140 – Pancreatic 120–140 – Small bowel Oral rehydration therapy (ORT) As a worldwide problem diarrhoea is by far the most important indication for fluid and electrolyte replacement. Intestinal absorption of sodium and water is enhanced by glucose (and other carbohydrates). Replacement of fluid and electrolytes lost through diarrhoea can therefore be achieved by giving solutions containing sodium, potassium, and glucose or another carbohydrate such as rice starch. Oral rehydration solutions should: . enhance the absorption of water and electrolytes; . replace the electrolyte deficit adequately and safely; . contain an alkalinising agent to counter acidosis; . be slightly hypo-osmolar (about 250 mmol/litre) to prevent the possible induction of osmotic diarrhoea; . be simple to use in hospital and at home; . be palatable and acceptable, especially to children; . be readily available. It is the policy of the World Health Organization (WHO) to promote a single oral rehydration solution but to use it flexibly (e.g. by giving extra water between drinks of oral rehydration solution to moderately dehydrated infants). The WHO oral rehydration salts formulation contains sodium chloride 2.6 g, potassium chloride 1.5 g, sodium citrate 2.9 g, anhydrous glucose 13.5 g. It is dissolved in sufficient water to produce 1 litre (providing Na+ 75 mmol, K+ 20 mmol, Cl– 65 mmol, citrate 10 mmol, glucose 75 mmol/litre). This formulation is recommended by the WHO and the United Nations Children’s fund, but it is not commonly used in the UK. Oral rehydration solutions used in the UK are lower in sodium (50–60 mmol/litre) than the WHO formulation since, in general, patients suffer less severe sodium loss. Millimoles per litre Ca2+ – Cl– HCO3 2.5 – – – – – – Blood and nutrition – – – – – – – – – – – – – – Millimoles per litre K+ – Cl– HCO3 5–20 100–150 – 5–15 30–50 80–120 5–15 70–110 40–80 5–15 20–40 90–130 Rehydration should be rapid over 3 to 4 hours (except in hypernatraemic dehydration in which case rehydration should occur more slowly over 12 hours). The patient should be reassessed after initial rehydration and if still dehydrated rapid fluid replacement should continue. Once rehydration is complete further dehydration is prevented by encouraging the patient to drink normal volumes of an appropriate fluid and by replacing continuing losses with an oral rehydration solution; in infants, breast- feeding or formula feeds should be offered between oral rehydration drinks. Oral bicarbonate Sodium bicarbonate is given by mouth for chronic acidotic states such as uraemic acidosis or renal tubular acidosis. The dose for correction of metabolic acidosis is not predictable and the response must be assessed. For severe metabolic acidosis, sodium bicarbonate can be given intravenously. Sodium bicarbonate may also be used to increase the pH of the urine; it is also used in dyspepsia. Sodium supplements may increase blood pressure or cause fluid retention and pulmonary oedema in those at risk; hypokalaemia may be exacerbated. Where hyperchloraemic acidosis is associated with potassium deficiency, as in some renal tubular and gastrointestinal disorders it may be appropriate to give oral potassium bicarbonate, although acute or severe deficiency should be managed by intravenous therapy. Parenteral preparations for fluid and electrolyte imbalance Electrolytes and water Solutions of electrolytes are given intravenously, to meet normal fluid and electrolyte requirements or to replenish substantial deficits or continuing losses, when the patient is nauseated or vomiting and is unable to take adequate amounts by mouth. When intravenous administration is not possible, fluid (as sodium chloride 0.9% p. 1101 or glucose 5% p. 1102) can also be given by subcutaneous infusion (hypodermoclysis). The nature and severity of the electrolyte imbalance must be assessed from the history and clinical and biochemical Blood and nutrition investigations. Sodium, potassium, chloride, magnesium, phosphate, and water depletion can occur singly and in combination with or without disturbances of acid-base balance. Isotonic solutions may be infused safely into a peripheral vein. Solutions more concentrated than plasma, e.g. 20% glucose, are best given through an indwelling catheter positioned in a large vein. Intravenous sodium Sodium chloride in isotonic solution provides the most important extracellular ions in near physiological concentrations and is indicated in sodium depletion, which can arise from such conditions as gastro-enteritis, diabetic ketoacidosis, ileus, and ascites. In a severe deficit of 4 to 8 litres, 2 to 3 litres of isotonic sodium chloride may be given over 2 to 3 hours; thereafter the infusion can usually be at a slower rate. Chronic hyponatraemia arising from inappropriate secretion of antidiuretic hormone should ideally be corrected by fluid restriction. However, if sodium chloride is required for acute or chronic hyponatraemia, regardless of the cause, the deficit should be corrected slowly to avoid the risk of osmotic demyelination syndrome and the rise in plasma- sodium concentration should not exceed 10 mmol/litre in 24 hours. In severe hyponatraemia, sodium chloride 1.8% may be used cautiously. Compound sodium lactate (Hartmann’s solution) can be used instead of isotonic sodium chloride solution during or after surgery, or in the initial management of the injured or wounded; it may reduce the risk of hyperchloraemic acidosis. Sodium chloride with glucose solutions p. 1102 are indicated when there is combined water and sodium depletion. A 1:1 mixture of isotonic sodium chloride and 5% glucose allows some of the water (free of sodium) to enter body cells which suffer most from dehydration while the sodium salt with a volume of water determined by the normal plasma Na+ remains extracellular. Combined sodium, potassium, chloride, and water depletion may occur, for example, with severe diarrhoea or persistent vomiting; replacement is carried out with sodium chloride intravenous infusion 0.9% and glucose intravenous infusion 5% with potassium as appropriate. Intravenous glucose Glucose solutions (5%) are used mainly to replace water deficit. Average water requirements in a healthy adult are 1.5 to 2.5 litres daily and this is needed to balance unavoidable losses of water through the skin and lungs and to provide sufficient for urinary excretion. Water depletion (dehydration) tends to occur when these losses are not matched by a comparable intake, as may occur in coma or dysphagia or in the elderly or apathetic who may not drink enough water on their own initiative. Excessive loss of water without loss of electrolytes is uncommon, occurring in fevers, hyperthyroidism, and in uncommon water-losing renal states such as diabetes insipidus or hypercalcaemia. The volume of glucose solution needed to replace deficits varies with the severity of the disorder, but usually lies within the range of 2 to 6 litres. Glucose solutions are also used to correct and prevent hypoglycaemia and to provide a source of energy in those too ill to be fed adequately by mouth; glucose solutions are a key component of parenteral nutrition. Glucose solutions are given in regimens with calcium and insulin for the emergency management of hyperkalaemia. They are also given, after correction of hyperglycaemia, during treatment of diabetic ketoacidosis, when they must be accompanied by continuing insulin infusion. Intravenous potassium Potassium chloride with sodium chloride intravenous infusion p. 1101 is the initial treatment for the correction of severe hypokalaemia and when sufficient potassium cannot be taken by mouth. Repeated measurement of plasma-potassium concentration is necessary to determine whether further infusions are required and to avoid the development of hyperkalaemia, which is especially likely in renal impairment. Initial potassium replacement therapy should not involve glucose infusions, because glucose may cause a further decrease in the plasma-potassium concentration. Bicarbonate and lactate Sodium bicarbonate p. 1099 is used to control severe metabolic acidosis (pH<7.1) particularly that caused by loss of bicarbonate (as in renal tubular acidosis or from excessive gastro-intestinal losses). Mild metabolic acidosis associated with volume depletion should first be managed by appropriate fluid replacement because acidosis usually resolves as tissue and renal perfusion are restored. In more severe metabolic acidosis or when the acidosis remains unresponsive to correction of anoxia or hypovolaemia, sodium bicarbonate (1.26%) can be infused over 3–4 hours with plasma-pH and electrolyte monitoring. In severe shock, for example in cardiac arrest, metabolic acidosis can develop without sodium or volume depletion; in these circumstances sodium bicarbonate is best given as a small volume of hypertonic solution, such as 50 mL of 8.4% solution intravenously. Sodium lactate intravenous infusion is no longer used in metabolic acidosis because of the risk of producing lactic acidosis, particularly in seriously ill patients with poor tissue perfusion or impaired hepatic function. For chronic acidotic states, sodium bicarbonate can be given by mouth. Plasma and plasma substitutes Plasma and plasma substitutes (‘colloids’) contain large molecules that do not readily leave the intravascular space where they exert osmotic pressure to maintain circulatory volume. Compared to fluids containing electrolytes such as sodium chloride and glucose (‘crystalloids’), a smaller volume of colloid is required to produce the same expansion of blood volume, thereby shifting salt and water from the extravascular space. If resuscitation requires a volume of fluid that exceeds the maximum dose of the colloid then crystalloids can be given; packed red cells may also be required. Albumin solution p. 1109, prepared from whole blood, contain soluble proteins and electrolytes but no clotting factors, blood group antibodies, or plasma cholinesterases; they may be given without regard to the recipient’s blood group. Albumin is usually used after the acute phase of illness, to correct a plasma-volume deficit; hypoalbuminaemia itself is not an appropriate indication. The use of albumin solution in acute plasma or blood loss may be wasteful; plasma substitutes are more appropriate. Concentrated albumin solution (20%) can be used under specialist supervision in patients with an intravascular fluid deficit and oedema because of interstitial fluid overload, to restore intravascular plasma volume with less exacerbation of the salt and water overload than isotonic solutions. Concentrated albumin solution p. 1109 may also be used to obtain a diuresis in hypoalbuminaemic patients (e.g. in hepatic cirrhosis). Recent evidence does not support the previous view that the use of albumin increases mortality. Plasma substitutes Dextran, gelatin p. 1110, and the hydroxyethyl starch, tetrastarch, are macromolecular substances which are metabolised slowly. Dextran and gelatin may be used at the outset to expand and maintain blood volume in shock arising from conditions such as burns or septicaemia; they may also be used as an immediate short-term measure to treat haemorrhage until blood is available. Dextran and gelatin are rarely needed when shock is due to sodium and water depletion because, in these circumstances, the shock responds to water and electrolyte repletion. Hydroxyethyl starches should only be used for the treatment of hypovolaemia due to acute blood loss when crystalloids alone are not sufficient; they should be used at the lowest effective dose for the first 24 hours of fluid resuscitation. Plasma substitutes should not be used to maintain plasma volume in conditions such as burns or peritonitis where there is loss of plasma protein, water, and electrolytes over periods of several days or weeks. In these situations, plasma or plasma protein fractions containing large amounts of albumin should be given. Large volumes of some plasma substitutes can increase the risk of bleeding through depletion of coagulation factors. BICARBONATE
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Driving and skilled tasks Manufacturer advises that patients and their carers should be counselled on the effects on driving and the performance of skilled tasks— increased risk of dizziness.
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Initially 1 microgram/kg once weekly, adjusted
First-line fragment. Read the complete Indications and Dose section above.
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