Nausea and vomiting are common symptoms that. Drug review Nausea and vomiting

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1 Drug review Nausea and vomiting Recommended management of nausea and vomiting Rachael Fallon MBA, MRPharmS, ClinDipPharm, Christopher Fraser MD, MRCP and Kieran Moriarty CBE, MD, FRCP Skyline Imaging Ltd The underlying cause of nausea and vomiting is usually elicited by taking a careful history; treatment can then be initiated in combination with a suitable antiemetic. This Drug Review considers the properties and roles of the drugs currently used to treat nausea and vomiting, followed by sources of further information and the Datafile. Nausea and vomiting are common symptoms that all individuals will experience at some time. Nausea may occur without vomiting and vice-versa. Most episodes of nausea and vomiting are transient and without ill-effect, but when prolonged or severe may cause significant morbidity, leading to increased use of health resources, eg by longer hospitalisation, and a reduction in productivity because of time away from the workplace. Treating nausea and vomiting effectively is therefore important not only to the patient but also for economic reasons. Causes A wide variety of disorders can induce nausea and vomiting. Common causes include diseases of the gastrointestinal tract and other abdominal viscera, infections, drugs, surgery or CNS pathology (see Table 1). Ingestion of exogenous toxins can, of course, induce vomiting; in this capacity emesis has a protective role, conveying a survival advantage. 50 Prescriber 19 October

2 Apart from motion (travel) sickness, this article will focus on nausea and vomiting of nonvestibular origin. Chronic nausea and vomiting is defined as the persistence of symptoms for more than one month and it usually presents more of a diagnostic challenge than acute nausea and vomiting since signs and symptoms pointing towards an aetiology may be more subtle. Neurophysiology The co-ordination of the various autonomic changes associated with emesis occurs at the level of the medulla oblongata of the hindbrain within an area known as the vomiting centre (VC). The VC is not a discrete anatomical site but rather a collection of interconnected neuronal networks, receiving afferent input from several loci including the nucleus tractus solitarius and vagus nerve (which monitors intestinal contents and gastric tone), the vestibular apparatus, centres within the cortex and limbic system (fear and anticipation) and the chemoreceptor trigger zone (CTZ). The CTZ is located in the area postrema of the brain s fourth ventricle on the blood side of the bloodbrain barrier (BBB). Chemosensitive receptors found here can therefore detect any circulating emetic agents (alcohol, cytotoxic drugs or chemicals) present in the blood and relay this information to the VC. The result of VC activity is a complex but coordinated modulation of swallowing control, respiratory function, salivation (to protect the buccal mucosa from the acidic stomach contents) and baroreceptor response combined with alterations in gastric and lower oesophageal sphincter tone, causing emesis to occur. The areas of the brain involved in the nausea and vomiting process and the main triggering factors are shown in Figure 1. Drug management Assessment of the patient presenting with nausea and vomiting begins with the differentiation of these symptoms from bulimia, regurgitation and rumination. It should include a clear delineation of the duration, frequency and severity of symptoms, together with their characteristics and the nature of any associated symptoms (see Table 1). Symptomatic therapy should be based on severity of symptoms and clinical context. The occasional episode of nausea and vomiting requires no treatment except rest, abstinence from food or alcohol and frequent small amounts of fluid. Mild nausea and uncomplicated vomiting may be treated empirically with oral antiemetics. Severe intractable episodes require fluid replacement, correction of electrolyte and acid-base abnormalities (eg hyponatraemia, hypokalaemia, metabolic alkalaemia) Medications and toxic causes analgesics, opioids, alcohol, digoxin, aminoglycosides, erythromycin, theophylline, azathioprine, dopamine agonists, high-dose oestrogens, chemotherapy, radiation Infectious causes gastroenteritis, otitis media, hepatitis, septicaemia Disorders of the gut and peritoneal cavity peptic ulcer disease, gastric outlet obstruction, small bowel obstruction, cancer, appendicitis, cholecystitis, mesenteric ischaemia, paraneoplastic syndromes, gastroparesis, functional dyspepsia CNS causes tumour, migraine, meningitis, labyrinthine disease, brainstem infarct/haemorrhage Endocrine and metabolic causes pregnancy and hyperemesis gravidarum, uraemia, diabetic ketoacidosis, hyperthyroidism, Addison s disease, hypercalcaemia, acute intermittent porphyria Postoperative nausea and vomiting gynaecological, abdominal or ear, nose and throat (ENT) surgery Cyclical vomiting syndrome Psychogenic or psychiatric disorders functional nausea and vomiting, anxiety disorders, depression, anorexia nervosa, bulimia nervosa Miscellaneous conditions myocardial infarction and cardiac failure, starvation, rumination, idiopathic Table 1. Common causes of nausea and vomiting and metabolic disturbances, as well as parenteral administration of agents such as metoclopramide, phenothiazines or serotonin 5HT 3 -antagonists. Identification of the underlying cause is usually established in most cases by taking a careful history followed by a thorough examination. Clinical features will point towards the underlying cause, and diagnostic tests should be directed by the clinical picture. Treatment should then be commenced in combination with the most suitable antiemetic drugs to suppress or eliminate symptoms. The management of these symptoms in specific clinical contexts reflects our understanding of their Prescriber 19 October

3 Chemoreceptor trigger zone Vomiting triggered by: drugs chemicals toxins antihistamines anticholinergics dopamine antagonists cannabinoids 5HT 3 -antagonists neurokinin receptor antagonist benzodiazepines gastric dysmotility: prokinetic agents 5HT 3 -antagonists neurokinin receptor antagonist Nucleus tractus solitarius Vomiting triggered by: surgery chemotherapy food poisoning Vomiting centre Vomiting triggered by: fear anticipation pain olfactory Figure 1. Triggers of the vomiting reflex and sites of action of antiemetic drugs pathophysiology and the neuropharmacology of available agents: thus, motion sickness and related disorders are treated primarily with histamine H 1 - and muscarinic M 1 -antagonists, whereas the prevention and treatment of acute postchemotherapy nausea and vomiting (PCNV) has come to be based largely on the use of 5HT 3 -antagonists. Phenothiazines, antihistamines and 5HT 3 -antagonists are used for postoperative nausea and vomiting (PONV). Aside from the management of PCNV- and PONVinduced nausea and vomiting, there have been few controlled trials comparing different therapeutic strategies or antiemetic agents in symptomatic therapy. As a result treatment is often empirical but an understanding of the neuropharmacology of available antiemetic drugs is important, since there are several classes of agents available that antagonise the neurotransmitter receptors involved in the physiology of emesis. A list of the various groups of antiemetics is shown in Table 2. In addition to the antiemetics, prokinetics may be a useful alternative, particularly when symptoms are believed to be secondary to gastroparesis or pseudo-obstruction. The sites of action of antiemetic and prokinetic agents are shown in Figure 1. The properties of the principal classes of drugs available for the treatment of nausea and vomiting are discussed below. Dopamine antagonists A summary of the most commonly used dopamine antagonists is provided in Table 3. Phenothiazines were the first group of drugs to demonstrate substantial activity in the prevention of chemotherapy-induced emesis. Prochlorperazine is most commonly used. Others include chlorpromazine, levomepromazine (Nozinan), perphenazine (Fentazin) and trifluoperazine. This class of drugs acts on the central dopamine D 2 -antagonists in the area Prescriber 19 October

4 dopamine antagonists phenothiazines, eg prochlorperazine substituted benzamides, eg metoclopramide butyrophenones, eg haloperidol antihistamines anticholinergics 5HT 3 -antagonists neurokinin receptor antagonist corticosteroids benzodiazepines cannabinoids Table 2. Groups of available antiemetic drugs postrema of the midbrain and also has muscarinic M 1 - and histamine H 1 -receptor blocking activity. Phenothiazines are moderately effective in nausea due to various gastrointestinal disorders and mild to moderate emetogenic chemotherapy. They are also useful for vertigo, motion sickness, migraine and PONV. Levomepromazine is useful as an adjunct in palliative care since it also relieves restlessness and distress at higher dosages. Their main side-effects are due to extrapyramidal reactions, eg akathisia, dystonia and tardive dyskinesia. These effects and neurotoxicity are exacerbated with lithium. Sedation and hypotension also occur. Hypotension may be enhanced with opioid analgesics, anaesthetics and antihypertensives. Benzamides These include metoclopramide and domperidone. Metoclopramide acts as a central and peripheral dopamine D 2 -antagonist at low doses and a weak serotonin-receptor blocker at higher doses. Metoclopramide is relatively ineffective in PONV. Domperidone only antagonises peripheral dopamine D 2 -receptors as it does not cross the BBB. Benzamides are effective in moderate to severe nausea. Higher doses were formerly combined with dexamethasone as the antiemetic regimen of choice for highly emetogenic chemotherapy, but have now largely been replaced by 5HT 3 -antagonists. They are still useful in PCNV as an adjunctive agent for prevention of delayed emesis, with first-line treatment failure or for those at low risk of emesis. Metoclopramide readily crosses the BBB and commonly causes extrapyramidal side-effects, especially in the elderly, patients under 20 years of age, those on concurrent treatment with an antipsychotic agent or if a high dosage is used. As domperidone does not cross the BBB it lacks the neurological side-effects of metoclopramide and is also a useful antiemetic for Parkinson s disease patients. Unlike metoclopramide, it is not available in injectable form, but is available orally or as a suppository. Both metoclopramide and domperidone can cause hyperprolactinaemia, resulting in galactorrhoea or gynaecomastia with prolonged use. Their use should be avoided in gastrointestinal tract obstruction, perforation or haemorrhage. Prokinetics Metoclopramide and domperidone also have prokinetic properties. They are used primarily in gastro-oesophageal reflux disease, gastroparesis, pseudo-obstruction and other dysmotility syndromes. Their use, however, is limited by their side-effects and long-term efficacy may be poor. As they enhance acetylcholine release from gastric smooth muscle cells, gastric emptying and lower oesophageal sphincter tone is increased. Metoclopramide has some efficacy in gastro-oesophageal reflux and gastroparesis. Domperidone is also used in functional dyspepsia. Domperidone 10mg tablets are available to buy over the counter for the relief of postprandial symptoms of excessive fullness, nausea, epigastric bloating and belching. Butyrophenones Haloperidol is a central dopamine D 2 -antagonist that is commonly used in palliative care. The side-effects of this drug are similar to phenothiazines but with less hypotension and sedation. Antihistamines These are histamine H 1 -antagonists that include cinnarizine, cyclizine (Valoid), meclozine (Sea-Legs) and promethazine. They are most effective when given before the onset of nausea and vomiting and they are primarily used for motion sickness, vertigo and migraine. Cyclizine is often used as a first-line drug in the prevention and treatment of PONV. Sedation is the commonest side-effect; other less frequent effects include dry mouth and blurred vision, as they are weak antimuscarinics. They may potentiate other CNS sedatives. Anticholinergics Anticholinergics act as muscarinic M 1 -antagonists and have a modest efficacy with poor tolerance. Their main use is in prophylaxis against motion sickness, the most commonly used being hyoscine (Scopoderm, see Figure 2). Main side-effects include dry mouth, drowsiness and visual disturbance. 54 Prescriber 19 October

5 5HT 3 -antagonists This group of drugs includes ondansetron (Zofran), granisetron (Kytril), dolasetron (Anzemet), tropisetron (Navoban) and palonosetron (Aloxi). They have similar tolerability and the oral and intravenous doses have similar efficacy and onset of action. Their antiemetic action is primarily the result of their effects on abdominal vagal afferents, although they also have a central effect. Cytotoxic agents used for chemotherapy increase serotonin release from small-intestinal mucosa, activating 5HT 3 -receptors on vagal abdominal afferents. Vagal afferent discharge to serotonin is completely abolished by the 5HT 3 - antagonists. The prevention and treatment of PCNV relies largely on the use of 5HT 3 -antagonists. They are the cornerstone for acute emesis with moderate to highly emetic chemotherapeutic agents, when they are often combined with dexamethasone. They are less effective in the management of delayed PCNV. 5HT 3 -antagonists are also useful in the management of PONV, where they are reserved for patients in whom other agents have failed or who have a history of severe PONV. The use of 5HT 3 -antagonists is thus predominantly in secondary care. Their side-effect profile is largely limited to mild headache, asthenia, constipation and dizziness, with no cognitive, psychomotor or affective disturbances. However, this class of drugs may cause ECG changes and therefore concomitant use of drugs that prolong the QT interval should be avoided. Neurokinin receptor antagonists This is a new class of antiemetic drugs that act as neurokinin 1 receptor antagonists. Currently only aprepitant (Emend), as an oral preparation, is available. This has been developed for use in combination with a 5HT 3 antagonist and a corticosteroid for the prevention of PCNV where it has a novel mechanism of action over available agents. Side-effects Drug name Usual oral Oral bio- Pharmaco- Half- Drug Side-effects Comments dose and availability kinetics life interactions frequency Prochlorperazine 5-10mg <10% extensive 7h other drugs sedation, available in several 2-3 times first-pass causing extrapyramidal formulations including daily metabolism hypotension reactions and buccal tablets, oral lithium hypotension liquid and injection Metoclopramide 10mg 3 >90% undergoes 4h antipsychotics extra- also available as times first-pass pyramidal an injection and daily metabolism; reactions, oral liquid clearance is restlessness can be used as a by hepatic and stimulation prokinetic agent; metabolism; of prolactin contraindicated in only 20% is release gastrointestinal excreted in patients with an the urine obstruction, unchanged perforation or haemorrhage Domperidone 10-20mg 13-17% undergoes 12- none stimulates less likely to cause 3-4 times extensive 16h significant prolactin extrapyramidal sidedaily presystemic release effects and sedation metabolism reduced libido also available as suppositories and oral liquid but not as an injection also has prokinetic properties Table 3. Summary of the properties of the most commonly used dopamine antagonists Prescriber 19 October

6 VM Figure 2. Hyoscine is available as a transdermal patch (Scopoderm) for motion sickness are favourable but include asthenia, fatigue and hiccups. Because aprepitant is an inhibitor and/or inducer of certain cytochrome P450 enzymes (CYP3A4, CYP2C9), concomitant use with other drugs metabolised by cytochrome enzymes should be avoided or closely monitored with doses modified according. Corticosteroids Dexamethasone has been the most extensively evaluated and used. Its mechanism of action is unknown but may relate to a reduction in prostaglandin levels. Dexamethasone is an effective and well-tolerated antiemetic for PCNV, and is usually combined with a 5HT 3 -antagonist for moderate to highly emetogenic chemotherapy. It is also the drug of choice for the prevention of delayed emesis after chemotherapy. Common side-effects include insomnia, increased energy and mood changes. Benzodiazepines Benzodiazepines are relatively weak antiemetic agents on their own, but may be used as adjunctive agents, reducing anxiety and akathisia associated with dexamethasone and metoclopramide respectively. They may also reduce anticipatory emesis. The main side-effects of benzodiazepines are sedation and amnesia. Cannabinoids The major psychoactive component of marijuana, tetrahydrocannabinol (THC), is useful therapeutically as an antiemetic. Synthetic cannabinoids include nabilone and dronabinol (the latter is not licensed for use in the UK). Nabilone is only available orally and is usually only used in the hospital setting. Modest antiemetic effects were first observed when marijuana was used during chemotherapy and trials confirm nabilone and dronabinol are effective. Sideeffects include euphoria, sedation, hypotension, dizziness, depression, paranoia, xerostomia and vertigo. These side-effects may limit its widespread use. Nausea and vomiting in pregnancy Special mention should be given to nausea and vomiting in pregnancy, since this affects at least 50 per cent of pregnant women. Onset is generally during the first trimester and is usually well tolerated; adequate fluid and electrolyte replacement is the most important factor in management. Nondrug options that may be effective in some women include ginger or acupressure at the Neiguan (P6) point in the wrist. In per cent of pregnancies vomiting may become severe and intractable (hyperemesis gravidarum) and it is reasonable to prescribe an antiemetic. The drug of choice is usually an antihistamine because of the considerable amount of experience with their use in pregnancy and the lack of evidence of adverse fetal effects. Either cyclizine or promethazine (as the teoclate salt, which is longer acting) may be used. Specialist advice should be sought if there is no improvement within hours. Caution should be exercised with the use of newer antiemetic agents where little is known of their potential teratogenic effects. Thiamine should be prescribed to prevent Wernicke s encephalopathy. Opioid-induced nausea and vomiting Opioids are thought to induce nausea and vomiting by a direct action on the CTZ, where all three types of opioid receptors (kappa, delta and mu) are thought to play a role. Stimulation of the opioid receptors results in nausea and vomiting in two-thirds of patients, and therefore the use of antiemetics must be considered when a patient is to start on a strong opioid such as morphine. Another reason for prescribing an antiemetic is that if a patient is prescribed oral morphine and vomits, future morphine doses will not be absorbed. Thus the patient remains in pain and loses confidence in the medicine. The patients most likely to be at risk of nausea and vomiting should therefore be prescribed an antiemetic agent, to be taken regularly when starting morphine treatment. These include patients who are already experiencing nausea and vomiting from 56 Prescriber 19 October

7 another cause, those who are experiencing or who have previously experienced nausea and vomiting with codeine or another weak opioid, and those who vomited when given a strong opioid in the past. The most commonly used treatment is a small dose of haloperidol orally. Other options include cyclizine and levomepromazine. A prokinetic agent may be useful in patients with vomiting secondary to delayed gastric emptying. 5HT 3 -antagonists do not reverse opioid-induced nausea and vomiting. With continued use, tolerance to opioid sideeffects may occur. This usually takes about one week, at which point the need for an antiemetic should be reviewed. If a patient has continued nausea and vomiting, consider stopping the opiate or reducing the dosage (as it is a dose-related side-effect), or changing the drug and reviewing the patient for other causes of nausea and vomiting. Migraine-induced nausea and vomiting Nausea and vomiting are common in patients with migraine. A number of antiemetic agents can be useful in migraine treatment, including metoclopramide, prochlorperazine and domperidone. Gastric motility is reduced during a migraine attack, which may impair absorption of oral analgesics and 5HT 1 -agonists (triptans). It may, therefore, be beneficial to use an antiemetic agent with a prokinetic action at the first signs of the onset of a migraine attack. Administering antiemetics to patients who are actively vomiting may be a problem. Intramuscular injections can be given in GP surgeries or hospitals, but suppositories and buccal tablets are a useful form of treatment that patients can administer themselves at home without resorting to medical help. Prochlorperazine 3mg buccal tablets (Buccastem) are also available to buy over the counter to treat nausea and vomiting in people aged 18 and over with previously diagnosed migraine. Motion sickness Labyrinthine disorders produce nausea and vomiting, often accompanied by vertigo. Motion sickness is associated with extensive autonomic activation resulting in pallor, sweating and salivation. It is induced by chronic repetitive movements, which stimulate afferent neural pathways projecting to the vestibular nuclei, leading to activation of the VC, triggering emesis. This activation is mediated primarily via histamine H 1 and muscarinic M 1 cholinergic rather than dopaminergic or serotonergic pathways; therefore, antihistamines and anticholinergics have assumed an important role in therapy. Available antihistamine agents include cyclizine, cinnarizine, meclozine and promethazine. Sedation is a common side-effect. Currently, the only anticholinergic agent that enjoys any degree of use is hyoscine, used orally (Kwells) or administered a few hours before travelling as a transdermal patch (Scopoderm). Side-effects include dry mouth, drowsiness and visual disturbance. Alternative remedies for the treatment of motion sickness range from herbs to acupressure. While there is little or no clinical evidence that supports the use of these remedies, some travellers find they work well. The most popular herbal treatment for nausea is ginger root in the form of capsules or tea. Acupressure has also been studied as a nondrug means of preventing motion sickness. To control nausea and vomiting, pressure is applied to the P6 acupuncture point using a wristband. Other advice to avoid motion sickness includes planning ahead before travelling: if this is by plane, ask for a seat over the front edge of a wing; if by train, take a seat near a window and face forward; if by coach or bus, sit near the front; if by car, drive or sit in the front passenger s seat. Do not read during the journey and focus on the horizon or on a distant, stationary object. Keep the head still, eg by resting it against a seat back, and do not smoke or sit near smokers. Avoid overeating, alcohol and spicy foods. Conclusion The management of nausea and vomiting depends on a careful history and examination. This usually identifies the underlying cause, and treatment can then be initiated, including the trial of an appropriate antiemetic agent. The 5HT 3 -antagonists offer a Forum If you have any issues you would like to air with your colleagues or comments on articles published in Prescriber, the Editor would be pleased to receive them and, if appropriate, publish them on our Forum page. Please send your comments to: The Editor, Prescriber, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, or to prescriber@wiley.co.uk Prescriber 19 October

8 particularly effective therapy for controlling symptoms, and the emergence of newer antiemetic therapies will increase the choices already available for a condition that proves difficult to treat effectively. References American Gastroenterological Association medical position statement: nausea and vomiting. Gastroenterology 2001; 120: Dando T, Perry CM. Aprepitant. A review of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs 2004:64(7): Gregory RE, Ettinger DS. 5HT 3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting: a comparison of their pharmacology and clinical efficacy. Drugs 1998;55: Hornby PJ. Central neurocircuitry associated with emesis. Am J Med 2001;111(Suppl 8A):106S-12S. Keefe DL. The cardiotoxic potential of 5-HT 3 receptor antagonist antiemetics: Is there cause for concern? The Oncologist 2002:7(1): Lee A. Common problems in pregnancy. In: Lee A, Inch S, Finnigan D, eds. Therapeutics in pregnancy and lactation. Abingdon: Radcliffe Medical Press, P switch proposed for prochlorperazine. Pharmaceutical J 2001;266: Resources Further reading Nausea and vomiting: overview, challenges, practical treatments and new perspectives: for primary care professionals, multidisciplinary students, and all persons thoughtful and curious. Blum RH, ed. London: Whurr, Groups and organisations Migraine Action Association, Unit 6, Oakley Hay Lodge Business Park, Great Folds Road, Great Oakley, Northants NN18 9AS. Tel: ; fax: ; website: Postoperative nausea and vomiting time for balanced antiemesis? (Editorial.) Br J Anaesth 2000;85: Quigley EMM, Hasler WL, Parkman HP. AGA technical review on nausea and vomiting. Gastroenterology 2001; 120: Regnard CFB, Tempest S, eds. A guide to symptom relief in advanced disease. 4th ed. Hale: Hochland and Hochland Ltd, Reynolds DJM, Blogg CE. Prevention and treatment of postoperative nausea and vomiting. Prescr J 1995;35(3): Sheehan O, Feely J, Bonnar J. Treating common medical conditions in pregnancy: 3. Prescriber 1999;10(6): The gastrointestinal tract. In: Rang HP, Dale MM, Ritter JM, et al, eds. Pharmacology 5th ed. London: Churchill Livingstone, 2003: Tramer MR, Carroll D, Campbel, et al. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 2001;323: Twycross RG, ed. Symptom management in advanced cancer. 2nd ed. Abingdon: Radcliffe Medical Press, Rachael Fallon is deputy director of pharmacy at Wirral Hospital NHS Trust, Dr Fraser is a consultant gastroenterologist at St Mark s Hospital, London, and Dr Moriarty is consultant gastroenterologist at the Royal Bolton Hospital CancerBACUP, 3 Bath Place, Rivington Street, London EC2A 3JR. Tel: ; helpline: ; website: Macmillan Cancer Relief, 89 Albert Embankment, London SE1 7UQ. Tel: ; Cancerline: ; website: Marie Curie Cancer Care, 89 Albert Embankment, London SE1 7TP. Tel: ; website: Datafile: Drugs used to treat nausea and vomiting Drug Available as Form/strength Adult daily dosage range 1 Cost 2 Antidopaminergics domperidone Motilium 10mg tabs 10-20mg orally 3-4 times daily mg per ml susp or 30-60mg rectally twice daily mg supps domperidone 10mg tabs typical dosage based on BNF/MIMS 2 NHS cost of 28 days treatment at dosage stated. Prices from MIMS and Drug Tariff, September Prescriber 19 October

9 Datafile Drugs used in nausea and vomiting (cont.) Drug Available as Form/strength Adult daily dosage range 1 Cost 2 Antidopaminergics (cont.) metoclopramide 3 Maxolon 10mg tabs 5mg 3 times daily (for adults mg per 5ml syrup 30-59kg), 10mg 3 times daily (also paediatric (for adults over 60kg) soln and injection) Maxolon SR 15mg sust-rel caps 15mg twice daily (not suitable for 7.01 adults under 60kg) metoclopramide 10mg tabs 10mg 3 times daily 4.38 Antihistamines cyclizine Valoid 50mg tabs 50mg 3 times daily 6.22 (also injection) promethazine Avomine 25mg tabs 25mg 1-4 times daily Phenothiazines chlorpromazine chlorpromazine 25mg, 50mg, 100mg mg daily in 3 divided doses tabs 25mg per 5ml elixir perphenazine Fentazin 2mg, 4mg tabs 12mg daily in divided doses prochlorperazine Buccastem 3mg buccal tabs 3-6mg twice daily maleate Stemetil 5mg tabs prevention: 5-10mg 2-3 times daily (tabs) 5mg per 5ml syrup treatment: 20mg then 10mg 2 (also injection) hours later if required prochlorperazine 5mg tabs 5-10mg 2-3 times daily trifluoperazine Stelazine 1mg tabs 2-4mg daily in divided doses mg per 5ml syrup mg per ml oral soln trifluoperazine 1mg, 5mg tabs mg per 5ml sugar free oral soln 5HT 3 -antagonists dolasetron Anzemet 50mg, 200mg tabs chemotherapy: 200mg 1 hour before 50mg: 3/ chemotherapy 200mg: 3/ postoperative: 50mg shortly before anaesthetic delayed nausea and vomiting: 200mg daily for up to four days granisetron Kytril 1mg, 2mg tabs 2mg daily: first dose administered (also paediatric 1 hour before chemotherapy soln and injection) 1 typical dosage based on BNF/MIMS 2 NHS cost of 28 days treatment at dosage stated. Prices from MIMS and Drug Tariff, September all metoclopramide doses are for adults >20 years 4 5 days treatment 60 Prescriber 19 October

10 Datafile Drugs used in nausea and vomiting (cont.) Drug Available as Form/strength Adult daily dosage range 1 Cost 2 5HT 3 -antagonists (cont.) ondansetron Zofran 4mg, 8mg tabs postoperative: 8mg orally 1 hour 4mg: 30/ , prior to anaesthesia followed by 2 8mg: 10/ mg, 8mg Melt further doses of 8mg at 8-hourly 4mg: 10/ 35.97, tabs intervals; alternatively, 16mg single 8mg: 10/ mg per 5ml dose 1 hour prior to anaesthesia 50ml/ sugar-free soln chemotherapy and radiotherapy: 16mg supps 8mg orally or 16mg rectally 1-2 1/ (also injection) hours before therapy, then 8mg orally 12 hours later and twice daily, or 16mg rectally daily, for up to 5 days tropisetron Navoban 5mg caps chemotherapy: 5mg each morning (also injection) 1 hour before food for 5 days following pretherapy injection NK 1 -antagonist aprepitant Emend 80mg, 125mg caps chemotherapy: 125mg 1 hour before 3 day pack: chemotherapy, then 80mg in the (1x125mg and morning for next 2 days (to be used 2x80mg) in combination with a 5HT 3 -antagonist and corticosteroid) 1 typical dosage based on BNF/MIMS 2 NHS cost of 28 days treatment at dosage stated (unless otherwise indicated). Prices from MIMS and Drug Tariff, September all metoclopramide doses are for adults >20 years 4 5 days treatment Drugs used to treat motion sickness Drug Available as Form/strength Adult daily dosage range 1 Cost 2 Anticholinergic hyoscine Scopoderm 1.5mg patch 1 patch 5-6 hours before journey; 2 patches: 4.30 hydrobromide 1 after 72 hours if necessary Antihistamines cinnarizine Stugeron 15mg tabs 30mg 2 hours before, then 15mg 15/ 1.36 cinnarizine 15mg tabs every 8 hours during journey 84/ 7.08 cyclizine Valoid 50mg tabs 50mg 3 times daily 6.22 (also injection) promethazine Avomine 25mg tabs 25mg to be taken the night before 28/ 3.13 hydrochloride a long journey or 1-2 hours before short journeys Phenergan 10mg, 25mg tabs 20-25mg to be taken the night 10mg: 56/ mg per 5ml elixir before journey, repeated after 25mg: 56/ 3.06 (also injection) 6-8 hours as required 100ml: typical adult dosage 2 NHS cost of treatment at dosage stated. Prices from MIMS and Drug Tariff, September Prescriber 19 October