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CHAPTER 1 Second line drugs – alternatives (often in specific conditions) in both primary and secondary care First line drugs – drugs recommended in both primary and secondary care GASTRO-INTESTINAL SYSTEM Specialist drugs – where a specialist input is needed (see introduction for definition) Specialist only drugs – prescribing within specialist service only Page 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 Date 08/10 04/11 05/12 01/13 03/13 06/14 10/14 11/14 12/14 02/15 03/15 07/15 09/15 10/15 11/15 08/16 09/16 04/17 Dyspepsia and gastro-oesophageal reflux disease Antispasmodics and other drugs altering gut motility Ulcer healing drugs Dyspepsia Management Guidelines ~ Summary Acute diarrhoea Chronic bowel disorders Laxatives Local preparations for anal and rectal disorders Stoma care Drugs affecting intestinal secretions Additional NICE Guidance Revision 1.5 (NICE guidance), 1.6 (NICE guidance) 1.6 (NICE guidance), minor amendment 1.9.2 (drug addition), 1.5.2 (drug deletion) 1.3.5 (Updated MHRA Drug Safety) 1.5.3 (NICE guidance) 1.2, 1.5 (MHRA drug safety update) 1.6 (NICE guidance) 1.3 (NICE guidance) 1.6( Reformatting) 1.6 (Drug addition) 1.6 (NICE guidance) 1.5 (NICE guidance) 1.5 (NICE guidance), (drug amendment) 1.9 (minor amendment) 1.5 (NICE guidance) 1.6 (NICE guidance) 1.5 (NICE guidance) NICE Guidance NICE Guidance 1.5 (Minor amendment) First line drugs Second line drugs Specialist drugs 2 2 3 3 7 7 9 13 12 12 14 Contributor G Ells G Ells G Ells A Luck G Ells G Ells G Ells G Ells G Ells G Ells G Ells G Ells G Ells G Ells G Ells G Ells G Ells G Ells Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 1 of 14 1.1 Dyspepsia and gastro-oesophageal reflux disease 1.1.1 Antacids and simeticone Mixture Asilone MixtureSF Magnesium (Contains about 6mmol of sodium in trisilicate Co-magaldrox (Mucogel®) 10ml, laxative) SuspensionSF 195/220 (Low sodium, bowel neutral) 1.1.2 Compound alginates and proprietary indigestion preparations Tablets (Contains about 1mmol sodium Gastrocote per tablet) Infant Gaviscon® Peptac® Infacol® Oral powderSF (Contains 0.92mmol of sodium per dose) SuspensionSF (Contains 6.2mmol of sodium in 10ml) LiquidSF Notes: 1. Alginate containing products have low acid suppressant activity and should be reserved for patients with reflux symptoms. 2. Peptac® contains sodium alginate 250mg, sodium bicarbonate 133.5mg and calcium carbonate 80mg in 5ml. Peptac® has been included as the first choice alginate. 3. Infacol® contains activated dimeticone and may be useful in gripes, colic or wind pains. 1.2 Antispasmodics and other drugs altering gut motility Antispasmodics N.B. modified release tablets are excluded Tablets 135mg Mebeverine from formulary see below Peppermint oil Liquid 50mg in 5ml Capsules, enteric coated 0.2ml Alverine citrate Capsules 60mg, 120mg Hyoscine butylbromide Injection 20mg in 1ml Tablets 10mg 1. 2. Not modified release Mebeverine is included as a first line treatment, but it should be remembered that diet alone should be tried before any drug therapy. Dose is given 20 minutes before food, therefore no justification for twice daily MR tablets. Liquid preparation in swallowing difficulties only. Hyoscine butylbromide may be useful in gastro-intestinal disorders characterised by smooth muscle spasm and in terminal care, but its anticholinergic side effects limit its use. Drugs Altering Gut Motility (also appear in CNS chapter) Metoclopramide Domperidone Tablets 10mg Tablets 10mg MHRA drug safety update May 2014 Due to cardiac side effects, domperidone is now restricted to use in the relief of nausea and vomiting and should be used at the lowest effective dose for the shortest possible time. Domperidone is now contraindicated in people: o with conditions where cardiac conduction is, or could be, impaired o with underlying cardiac diseases such as congestive heart failure o receiving other medications known to prolong QT interval or potent CYP3A4 inhibitors o with severe hepatic impairment First line drugs Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 2 of 14 1.3 Ulcer healing drugs Things To Consider About Acid Suppression 1. Take a good history. “Indigestion” does not necessarily mean give acid suppression. 2. Lifestyle changes should be pursued. Patients should be advised to: Avoid large meals shortly before retiring to bed Reduce the amount of fat in their diet Raise the head of the bed at night 3. In the event that NSAIDs are required rather than simple analgesics, use the less GI toxic agent (ibuprofen, naproxen). All NSAIDs, including coxibs, have the propensity to cause serious GI events so should only be used after careful consideration. In those at risk, a PPI, ranitidine or misoprostol may be considered for protection against NSAID associated gastric and duodenal ulcers. Dyspepsia Management Guidelines ~ Summary NICE CG184: Dyspepsia and gastro‑ oesophageal reflux disease: Investigation and management of dyspepsia, symptoms suggestive of gastro‑ oesophageal reflux disease, or both A. Patients with dyspepsia in whom diagnostic endoscopy is appropriate. 1. Review medications for possible causes of dyspepsia (eg. theophyllines, bisphosphonates, corticosteroids & NSAIDs). In patients requiring referral, suspend NSAID use. 3. Pre treatment with anti-secretory drugs may mask significant diagnoses at endoscopy. For patients having their first endoscopy, it is advised that they stop their treatment 2 weeks before. B. Interventions for uninvestigated dyspepsia 1. Initial theraputic strategies for dyspepsia are empirical treatment with a PPI or testing for and treating H. pylori. A 2-week washout period following PPI use is necessary before testing for H. pylori with a breath test, therefore it is preferable to test for H Pylori first and treat if necessary (result is available within 24 to 48 hours) to avoid a patient starting a PPI and then having to stop prior to a test. 2. Offer empirical full-dose PPI therapy for 4 weeks to people with dyspepsia. 3. If there is an inadequate response to a PPI, offer H2 receptor antagonist (H2RA) therapy instead. C. Interventions for gastro-oesophageal reflux disease (GORD) 1. Offer patients who have GORD a full dose PPI for 4-8 weeks. 2. If symptoms recur following initial treatment, offer a PPI at the lowest dose possible to control symptoms, with a limited number of repeat prescriptions. 3. Discuss with people how they can manage their own symptoms by using the treatment when they need it. 4. If there is an inadequate response to a PPI offer H2RA therapy instead. 5. Offer people a full-dose PPI for 8 weeks to heal severe oesophagitis, taking into account the person's preference and clinical circumstances (for example, underlying health conditions and possible interactions with other drugs). 6. If initial treatment for healing severe oesophagitis fails, consider a high dose of the initial PPI, switching to another full-dose PPI or switching to another high-dose PPI. 7. Offer a full-dose PPI long-term as maintenance treatment for people with severe oesophagitis, taking into account the person's preference and clinical circumstances (for example, tolerability of the PPI, underlying health conditions and possible interactions with other drugs), and the acquisition cost of the PPI. 8. If the person's severe oesophagitis fails to respond to maintenance treatment, carry out a clinical review. Consider switching to another PPI at full dose or high dose and/or seeking specialist advice. D. Interventions for peptic ulcer disease 1. Offer H. pylori eradication therapy to H. pylori positive patients who have peptic ulcer disease. 2. For patients using NSAIDs with diagnosed peptic ulcer, stop the use of NSAIDs where possible. Offer full-dose PPI for 2 months to these patients and if H. pylori is present, subsequently offer eradication therapy. 3. Offer people with gastric ulcer and H pylori repeat endoscopy 6 to 8 weeks after beginning treatment, depending on the size of the lesion. First line drugs Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 3 of 14 4. Offer people with peptic ulcer (gastric or duodenal) and H pylori retesting for H pylori 6 to 8 weeks after beginning treatment, depending on the size of the lesion. 5. If symptoms recur after initial treatment, offer a PPI to be taken at the lowest dose possible to control symptoms. Discuss using the treatment on an 'as needed' basis with people to manage their own symptoms. E. Interventions for functional dyspepsia 1. Management of endoscopically determined non-ulcer dyspepsia involves initial treatment for H. pylori if present, followed by symptomatic management and periodic monitoring. 2. Re-testing after eradication should not be offered routinely, although the information it provides may be valued by individual patients. 3. If H. pylori has been excluded and symptoms persist, offer either a low-dose PPI or an H2RA for 4 weeks. 4. If symptoms continue or recur after initial treatment, offer a PPI or H2RA to be taken at the lowest dose possible to control symptoms. 5. Discuss using PPI treatment on an 'as-needed' basis with people to manage their own symptoms. F. Reviewing patient care 1. Offer patients requiring long-term management of symptoms for dyspepsia an annual review of their condition, encouraging them to try stepping down or stopping treatment (unless there is an underlying condition or co-medication that needs continuing treatment). 2. A return to self-treatment with antacid and/or alginate therapy (either prescribed or purchased over- the-counter and taken as required) may be appropriate. G. H. pylori testing and eradication Pylobactell® 1. H. pylori can be initially detected using carbon urea breath test or laboratory-based serology where its performance has been locally validated. The C urea breath test has a high sensitivity and specificity (>98%) and is non-invasive and is therefore the investigation of choice in primary care. 2. Surgery/office-based serological tests for H. pylori cannot be recommended because of their inadequate performance. In secondary care a stool antigen test may be used. 3. For patients who test positive provide eradication therapy as below taking into consideration: a. Antibiotic allergies b. Previous exposure to clarithromycin and metronidazole c. Acquisition cost Suggested regime for the eradication of Helicobacter pylori PPI Lansoprazole caps 30mg bd or Omeprazole caps 20mg bd + amoxicillin 1g BD + Clarithromycin OR metronidazole 500mg BD all for 7 days 400mg bd OR For penicillin allergic patients PPI Lansoprazole caps 30mg bd or Omeprazole caps 20mg bd + clarithromycin 500mg BD + metronidazole 400mg BD all for 7 days OR First line drugs Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 4 of 14 For penicillin allergic patients with previous exposure to clarithromycin PPI Lansoprazole caps 30mg bd or Omeprazole caps 20mg bd + bismuth 240mg BD +metronidazole 400mg BD + tetracycline 1g BD all for 7 days Second-line treatment 1. Offer people who still have symptoms after first-line eradication treatment a 7-day, twice-daily course of treatment with PPI, amoxicillin and the alternative antibiotic they did not receive as first line treatment. 2. Offer people who have had previous exposure to clarithromycin and metronidazole a 7-day, twice-daily course of treatment with a PPI, amoxicillin and a quinolone or tetracycline (whichever has the lowest acquisition cost). 3. Offer people who are allergic to penicillin (and who have not had previous exposure to a quinolone) a 7day, twice-daily course of treatment with a PPI, metronidazole and levofloxacin. 4. Offer people who are allergic to penicillin and who have had previous exposure to a quinolone a PPI, bismuth, metronidazole and tetracycline. 5. Seek advice from a gastroenterologist if eradication of H pylori is not successful with second-line treatment. 1.3.1 H2-receptor antagonists Ranitidine Cimetidine Tablets 150mg, 300mg Effervescent tablets 150mg Injection 50mg in 2ml Oral solution 75mg in 5ml Tablets 200mg, 400mg, 800mg Oral solution 200mg in 5ml Start dose 150mg bd. If symptoms not controlled with 300mg bd use PPI. Cimetidine is recommended second-line due to its interactions with anticoagulants, anti-epileptics, ciclosporin, theophylline and anti-arrhythmics. Effervescent tablets and liquid formulations should only be used in children where dosing requires it and in adults with swallowing difficulties 1.3.3 Chelates and complexes Sucralfate Tripotassium Dicitratobismuthate De-noltab® Tablets 1g Oral Suspension 1g in 5ml Tablets 120mg Sucralfate®: Following reports of bezoar formation associated with sucralfate, the CSM has advised caution in seriously ill patients, especially those receiving concomitant enteral feeds or those with predisposing conditions such as delayed gastric emptying. De-Noltab® requires counselling on correct administration. Can blacken faeces and darken tongue. De-Noltab® is only to be used as part of quadruple eradication therapy. 1.3.4 Prostaglandin analogues Misoprostol Tablets 200 micrograms Misoprostol is included as one option for NSAID prophylaxis. However, NSAIDs should be avoided in patients with dyspepsia wherever possible and a PPI is the preferred agent for gastroprotection. Refer also to NSAID section in BNF chapter 10. Effective contraception must be used in women of childbearing age. Contraindicated in pregnancy. The dose of misoprostol required to treat benign gastric and duodenal ulceration or NSAID-associated ulceration is 800micrograms per day in divided doses. However, colic and diarrhoea may limit the dose. First line drugs Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 5 of 14 1.3.5 Proton Pump Inhibitors (PPIs) CAUTION: Proton Pump Inhibitors may relieve or mask the symptoms from a malignant gastric ulcer and may even induce the healing of a lesion and therefore delay diagnosis. Where a PPI is indicated the LOWEST EFFECTIVE DOSE should be prescribed. Indication Omeprazole (O) / Lansoprazole (L) (capsules) Treatment of Gastro-oesophageal reflux disease O: 20mg daily for 4-8 weeks, L: 30mg daily for 4-8 weeks, If symptoms recur step down to lowest dose needed to control symptoms. Discuss use on an as-needed basis O: 40mg daily for 8 weeks, L: 30mg daily for 8 weeks, Long term maintenance as above Failure of treatment: Treatment of Gastro-oesophageal reflux disease - severe oesophagitis Try a different PPI as above or: O: 40mg twice a day, L: 30mg twice a day Maintenance: O: 40mg daily L: 30mg daily O: 20mg daily for 4 weeks L: 30mg daily for 4 weeks If symptoms recur step down to lowest dose needed to control symptoms. Discuss use on an as-needed basis O: 20mg daily for 4 weeks Maintenance of recurrent ulcers 20mg daily L: 30mg daily for 4 weeks; maintenance 15mg daily O: 20mg daily for 8 weeks L: 30mg daily for 8 weeks Zollinger-Ellison Syndrome O: 20-120mg daily L: 60 – 120mg daily O: 20mg daily for 4 weeks, continue for further 4 weeks if not fully healed. L: 30mg daily for 4 weeks, continued for further 4 weeks if not fully healed. Prophylaxis 15-30mg daily. O: 20mg daily L: 15-30mg daily Uninvestigated dyspepsia Duodenal Ulcer Gastric Ulcer NSAID associated ulcers NSAID Protection PPIs are not indicated for use in: Non-specific abdominal symptoms such as bloating or flatulence Right or left quadrant abdominal discomfort / pain Lower abdominal discomfort / pain MHRA Drug Safety Update – Interaction between the use of clopidogrel and PPI’s – April 2010 In light of the most recent evidence, the previous advice on the concomitant use of clopidogrel with proton pump inhibitors has now been modified. Use of either omeprazole or esomeprazole with clopidogrel should be discouraged. The current evidence does not support extending this advice to other PPIs. Lansoprazole Omeprazole Pantoprazole First line drugs Capsules 15mg, 30mg Orodispersible tablets 15mg, 30mg Capsules 20mg, 40mg Dispersible tablets 10mg, 20mg Injection 40mg Tablets 20mg, 40mg Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 6 of 14 Omeprazole injection indicated in acute GI bleed (confirmed by endoscopy or frank haematemesis, life threatening GI bleed, bleeding varices). NBM is not an indication for use of the injection. Orodispersible and dispersible tablets should only be used in children where dosing requires it and in adults with swallowing difficulties 1.4 Acute diarrhoea 1.4.2 Antimotility drugs Capsules 2mg Loperamide Codeine phosphate Oral syrup in swallowing difficulties only SyrupSF Oral 1mg / 5ml Tablets 15mg, 30mg, 60mg Notes: 1. A diagnosis of the cause of diarrhoea should be made before starting symptomatic treatment and acute prescriptions should be restricted to 12 loperamide capsules or 20 codeine tablets. 2. Diarrhoea should normally be managed with electrolyte replacement only. Anti-motility drugs should be restricted to short term use only. 3. The maximum dosage for loperamide is 16mg daily (8 capsules). 4. Codeine has addictive properties and should be reserved for short courses unless specialist involvement. 1.5 Chronic bowel disorders Treatment of ulcerative colitis and Crohn’s disease Subcutaneous injection Humira® 40mg pre-filled syringe Adalimumab Golimumab Infliximab Vedolizumab▼ 40mg pre-filled pen 40mg vial Simponi® 50mg, 100mg pre-filled pen Inflectra®▼ 100mg vial Remicade® 100mg vial Remsima▼ 100mg vial Entyvio® 300mg vial Subcutaneous injection Biosimilar - 1st choice Prescribe by brand Biosimilar - 1st choice IV infusion Two biosimilar versions of infliximab are now available. They originate from the same manufacturer hence either can be used when a biosimilar version of infliximab has been prescribed. NICE Guidance TA 187: Crohn’s disease – Infliximab (review) and adalimumab (review of TA 40) May 2010 Infliximab and adalimumab are recommended as treatment options for adults with severe active Crohn’s disease (Crohn’s Disease Activity Index score of 300 or more and a Harvey-Bradshaw Index of 8/9 or above). and whose disease has not responded to conventional therapy (including immunosuppressive and/or corticosteroid treatments), or who are intolerant of or have contraindications to conventional therapy. Infliximab is also recommended as a treatment option in the flowing circumstances: For active fistulating Crohn’s disease where the condition has not responded to conventional treatments or where patients are intolerant of or have contraindications to conventional treatments. In patients aged 6-17 years with severe active Crohn’s disease whose disease has not responded to conventional therapy or where there is intolerance or contraindications to conventional therapy. Infliximab or adalimumab should be given as a planned course of treatment until treatment failure (including the need for surgery), or until 12 months after the start of treatment, whichever is shorter. A gastroenterologist experienced in the management of Crohn’s disease should prescribe and monitor these treatments. NICE Guidance TA 329: Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis (including a review of TA140 and TA262) Feb 2015 First line drugs Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 7 of 14 Infliximab, adalimumab and golimumab are recommended, within their marketing authorisations, as options for treating moderately to severely active ulcerative colitis in adults whose disease has responded inadequately to conventional therapy including corticosteroids and mercaptopurine or azathioprine, or who cannot tolerate, or have medical contraindications for, such therapies. Infliximab is recommended, within its marketing authorisation, as an option for treating severely active ulcerative colitis in children and young people aged 6–17 years whose disease has responded inadequately to conventional therapy including corticosteroids and mercaptopurine or azathioprine, or who cannot tolerate, or have medical contraindications for, such therapies. They should be given as a planned course of treatment until treatment fails (including the need for surgery) or until 12 months after starting treatment, whichever is shorter. Treatment should continue only if there is clear evidence of response as determined by clinical symptoms, biological markers and investigation, including endoscopy if necessary. People who continue treatment should be reassessed at least every 12 months to determine whether ongoing treatment is still clinically appropriate. A trial withdrawal from treatment should be considered for all patients who are in stable clinical remission. People whose disease relapses after treatment is stopped should have the option to start treatment again. NICE Guidance TA342: Vedolizumab for treating moderately to severely active ulcerative colitis (June 2015) recommends vedolizumab as an additional treatment option under the same conditions as laid out in TA 329 (Feb 2015) NICE Guidance TA352: Vedolizumab for treating moderately to severely active Crohn's disease after prior therapy recommends vedolizumab as an option for treating moderately to severely active Crohn's disease only if: a tumour necrosis factor‑ alpha inhibitor has failed (that is, the disease has responded inadequately or has lost response to treatment) or a tumour necrosis factor‑ alpha inhibitor cannot be tolerated or is contraindicated. Notes: MHRA drug safety update (April 2014): There is an increased risk of tuberculosis, or reactivation of latent tuberculosis, during treatment with tumour necrosis factor alpha (TNF-alpha) inhibitors. TNFalpha inhibitors are contraindicated in patients with active tuberculosis or other severe infections. Patients should be screened patients for active and latent tuberculosis before starting treatment with a TNF-alpha inhibitor and monitored closely for infectious diseases including tuberculosis before, during, and after treatment. 1.5.1 Aminosalicylates Balsalazide Capsules 750mg Mesalazine Olsalazine Octasa MR - tablets 400mg, 800mg Pentasa - tablets 500mg, granules 1g sachet, 2g sachet Retention enema 1g, suppositories 1g Capsules 250mg Tablets 500mg Sulfasalazine Tablets 500mg EC tablets 500mg Suspension 250mg/5ml First line drugs Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 8 of 14 Notes: 1. Mesalazine tablets are modified release and different brands may have different release characteristics and, therefore, are not interchangeable. Thus, prescribing should be by brand name. 2. Mesalazine suppositories are a useful alternative to steroid enemas in maintenance therapy. 3. Sulfasalazine is useful for patients with concomitant arthritis. 4. None of the newer aminosalicylates are any more effective than sulfasalazine, but may cause fewer side effects. 5. CSM Warning: It is recommended that patients receiving aminosalicylates should be advised to report any unexplained bleeding, bruising, purpura, sore throat, fever or malaise that occurs during treatment. A blood count should be performed and the drug stopped immediately if there is a suspicion of a blood dyscrasia. 6. Olsalazine is minimally absorbed in the small bowel and may offer advantages over mesalazine for distal colitis. 7. Balsalazide should only be prescribed for patients not responding to other aminosalicylates. 1.5.2 Corticosteroids Modified release capsules 3mg Budesonide Foam enema Hydrocortisone Tablets 5mg, 25mg (Non-enteric Prednisolone coated) Enema 20mg Foam enema 20mg Notes: 1. Steroids are the most appropriate treatment for acute disease but do not prevent relapse. 2. Hydrocortisone enema is appropriate initial treatment for relapse, but if the symptoms have not resolved within two weeks, then specialist advice should be sought. 3. Budesonide MR is licensed for the induction of remission in patients with mild to moderate Crohn’s disease affecting the ileum and / or ascending colon for up to 8 weeks. Refer to BNF or SPC for full details. 4. Please refer to BNF chapter 6 for other indications of corticosteroids. 1.5.3 Drugs affecting the immune response Tablets 25mg, 50mg Azathioprine Ciclosporin IV infusion 50mg in 1ml, 1ml amp, Unlicensed use 5ml amp Methotrexate Mercaptopurine Tablets 2.5mg Unlicensed use Puri-Nethol® Tablets 50mg Xaluprine® suspension 20mg in 1ml Unlicensed use NB: Tablets and suspension are NOT bioequivalent 5. Azathioprine and mercaptopurine have a role in maintenance of remission in people with Crohn’s disease. Methotrexate is also indicated where patients cannot tolerate or have contraindications to azathioprine and mercaptopurine or where these drugs are ineffective. See NICE CG152 (October 2012) 6. If switching formulation of mercaptopurine, full haematological monitoring is advised as the products are not bioequivalent. 7. Ciclosporin has a role in the hospital setting for severe acute ulcerative colitis under specialist supervision. – see NICE CG166 (June 2013) First line drugs Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 9 of 14 1.6 Laxatives It should be remembered that a change in bowel habit might indicate the need for investigation rather than an automatic prescription. A digital rectal examination (DRE) may be required to establish if there is faecal matter in the rectum, the amount and consistency and the need for enemas. Ref RCN guidelines “Digital Rectal examination and manual removal of faeces” April 2004. There is little evidence on which to judge the relative effectiveness and tolerability of individual laxatives. Therefore choice should be based on symptoms, patient preferences, side effects and cost of medicines. Care should be taken with bulk forming laxatives. Patients should be advised to take them immediately with adequate fluid, (ensuring at least 1.5 litres per day). Lactulose takes up to 48 hours to work but is often inappropriately used “when required”. It is unpleasant to take and compliance may be a problem. Its main clinical benefit is in the management of hepatic encephalopathy. It is important to ensure a minimum fluid intake of 1.5 litres per day. Laxido® should be reserved only for patients where other treatments have been ineffective. Caution: may cause electrolyte disturbances. (Idrolax® is a polyethylene glycol preparation without electrolytes if a salt free preparation is required). Ongoing reassessment of the patient’s bowel habit is essential. Oral Preparations Sachets 3.5g (Fybogel®) Ispaghula husk Time of onset 1 – 2 days Docusate sodium Lactulose Capsules 100mg Paediatric oral solution 12.5mg/5ml, 50mg/5ml Solution Bisacodyl Tablets 5mg 10 – 12 hours Senna Tablets 7.5mg sennosides Syrup 7.5mg sennosides in 5ml 8 – 12 hours Macrogols (polyethylene glycols) Laxido® and Idrolax® Sachets 6 – 12 hours Sodium picosulfate Capsules 2.5mg Elixir 5mg/5ml (paediatrics) Rectal preparations Rectal preparations should be used only after careful assessment, (including DRE if appropriate) and diagnosis of the underlying cause of the constipation. 20 – 60 minutes Suppositories 5mg (paediatric), 10mg Bisacodyl Glycerol Suppositories 1g, 2g, 4g 15 – 30 minutes Sodium citrate Micro-enema 450mg 5 – 15 minutes Co-danthramer Terminally ill patients Capsules 25/200, 37.5/500 Suspension 25/200 in 5ml, 75/1000 in 5ml Co-danthrusate Capsules 50/60 Suspension 50/60 in 5ml Methylnaltrexone▼ 12mg in 0.6ml SC injection First line drugs Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 10 of 14 1. The CSM (Current Problems in Pharmacovigilance volume 26, May 2000) have advised that the indications for danthron containing products has been restricted to constipation in terminally ill patients of all ages. Therefore, co-danthramer and co-danthrusate are included as Specialist Initiated Drugs. 2. Most terminally ill patients require both a softening agent and a stimulant laxative, for example, codanthrusate (or a cheaper alternative, such as lactulose, may suffice) + senna. 3. Phosphate enemas and arachis oil enemas have not been included as their use has declined with the availability of polyethylene glycols which are also licensed for the treatment of faecal impaction. Advice should be sought from the continence service. N.B. arachis oil should not be used in patients with a nut allergy. 4. Methylnaltrexone is an opioid antagonist licensed for the treatment of opioid induced constipation in advanced illness patients who are receiving palliative care when response to usual laxative therapy has not been sufficient. 5. Use of methylnaltrexone is currently restricted to hospices or on the advice of a palliative care physician. Guidelines for the Management of Constipation For guidance on the management of constipation in children and young people see NICE CG 99 Constipation in children and young people Where possible stop any drugs likely to cause constipation Ensure patient is properly positioned when sitting on the toilet as correct posture can make defecation easier and more comfortable. Constipation Dietary advice – high fibre content diets in association with adequate fluid intake (minimum 1.5 litres per day) are effective in increasing stool weight and bowel movement frequency. It should be tried for at least a month before its effects are determined. It should be used with caution in patients who have obstructive symptoms or faecal impaction. Caution: a high fibre diet may increase bloating. Soft Stool 1. Senna 2 –4 tablets at night PRN 2. Glycerol suppository PRN 3. Sodium Citrate micro-enema PRN Hard Stool 1. Docusate 100mg TDS 2. Sodium Citrate micro-enema PRN 3. Laxido® sachets. Use 1 to 3 sachets daily in divided doses in water as per manufacturer’s instructions. Chronic Constipation Dietary advice – high fibre content diets in association with adequate fluid intake (minimum 1.5 litres per day) are effective in increasing stool weight and bowel movement frequency. It should be tried for at least a month before its effects are determined. It should be used with caution in patients who have obstructive symptoms or faecal impaction. Caution: a high fibre diet may increase bloating. The use of laxatives is not always necessary. However laxative use may be appropriate if: No response to dietary changes. There is faecal impaction. Constipation or painful defecation is associated with illness, surgery or during pregnancy. The patient is elderly or has a poor diet. Constipation is drug induced. Patient has a medical condition in which bowel strain is undesirable. Also in preparation for investigations or procedures. Laxatives – The choice of laxative should be based on symptoms, patient preferences, side effects and the cost. (See table above for formulary choices). Laxido ® Faecal impaction 8 sachets in 1000ml water & consumed over 6 hours. Used for 3 days then re-assess. 1.6.5 Bowel cleansing solutions Klean-Prep® First line drugs Oral Powder Second line drugs Macrogol based Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 11 of 14 Citramag Powder, effervescent Magnesium based Fleet Phospho-soda® Oral solution Phosphate based Picolax® Oral Powder Sodium picosulphate + magnesium citrate Note: With bowel cleaning agents used as preparation for colonoscopy, CT or surgery, fluid intake is important. NPSA Rapid Response Report (RRR012) February 2009 The NPSA has issued guidance on procedures for the supply of bowel cleansing agents in order to reduce the risk of harm to patients from electrolyte imbalance and dehydration. They advise that: RRR012/1. A clinical assessment is undertaken by the clinician authorising the surgery or investigative procedure (including GPs using the direct access route) to ensure that there is no contraindication (e.g. clinical condition such as diverticulitis) or risks (e.g. concurrent medication such as diuretics) from the use of a bowel cleansing solution. RRR012/2. Use of a bowel cleansing solution is authorised by the clinician at the same time as the surgery or investigative procedure. This may be done by using the same form. RRR012/3. The clinician requesting the surgery or procedure and authorising the use of a bowel cleansing solution is responsible for ensuring that an explanation on the safe use of the product is provided to the patient or carer. RRR012/4. A safe system exists that involves an authorised clinical professional in the supply of the medicine and written information (including named contact) for each patient. See implementation checklist in supporting information for more details on this. 1.6.6 Peripheral opioid receptor antagonists Relistor® 12mg in 0.6ml SC Only for initiation by a physician with expertise in palliative care injection Moventig® tablets 12.5mg, Naloxegol▼ 25mg NICE TA 345 (July 2015) recommends naloxegol as an option for treating opioid induced constipation in adults whose constipation has not adequately responded to laxatives. An inadequate response is defined as opioid-induced constipation symptoms of at least moderate severity in at least 1 of the 4 stool symptom domains (that is, incomplete bowel movement, hard stools, straining or false alarms) while taking at least 1 laxative class for at least 4 days during the prior 2 weeks. If only 1 laxative class has been taken, this should be the stimulant type. Methylnaltrexone 1.6.7. Other drugs used in Constipation Linaclotide▼ Lubiprostone Prucalopride Constella® Capsules 290 micrograms Amitiza® Capsules 24 micrograms Resolor® Tablets 1mg, 2mg Linaclotide is licensed for use in moderate to severe IBS with constipation. It can be used where optimal or maximum tolerated doses of previous laxatives from different classes have not helped and where constipation has been present for at least 12 months. The effectiveness of linaclotide should be reviewed after 3 months. See NICE Clinical Guideline 61: Irritable Bowel Syndrome in Adults (Feb 2015) for other treatment options. Lubiprostone and Prucalopride are newer treatments licensed for use in chronic constipation. Lubiprostone is an option for treating chronic idiopathic constipation, in adults in whom treatment with at least 2 laxatives from different classes, at the highest tolerated recommended doses for at least 6 months, has failed to provide adequate relief and for whom invasive treatment for constipation is being considered NICE TA 318 (July 2014) Prucalopride is licensed for use in women only and is recommended as an option for the treatment of chronic constipation only in women for whom treatment with at least two laxatives from different classes, at the highest tolerated recommended doses for at least 6 months, has failed to provide adequate relief and invasive treatment for constipation is being considered. NICE TA 211 (Dec 2010) First line drugs Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 12 of 14 1.7 Local preparations for anal and rectal disorders 1.7.1 Soothing haemorrhoidal preparations Cream, 23g Anusol® (Soothing preparation) Anusol HC® (soothing plus steroid) Proctosedyl® (Local anaesthetic plus steroid) Xyloproct® Ointment, 25g Suppositories Ointment, 30g Suppositories Suppositories Ointment 30g Ointment, 30g (local anaesthetic plus steroid) Note: These preparations are of limited clinical value and should only be used for short periods (not more than a few days) as they cause sensitisation of the skin. Excessive application of preparations containing local anaesthetics should be avoided. 1.7.3 Rectal sclerosants Phenol, Oily Injection 5% in 5 ml 1.7.4 Management of anal fissures Glyceryl trinitrate rectal ointment 0.4% 1.8 Stoma care Stoma advice is available from the Stoma Care Clinical Nurse Specialists 1.9 Drugs affecting intestinal secretions 1.9.1 Drugs acting on the gall bladder Capsules 250 mg Ursodeoxy-cholic acid (Ursofalk®) Suspension 250mg in 5ml Note: Ursofalk® is included as it is licensed for primary biliary cirrhosis. 1.9.2 Bile acid sequestrants Questran® sachets 4g Colestyramine powder Questran Light® sachets 4g SF Note: Cholestyramine is indicated for pruritis associated with partial biliary obstruction and primary biliary cirrhosis. 1.9.4 Pancreatin Pancreatin First line drugs Creon® 10,000 capsules Creon® 25,000 capsules Creon® 40,000 capsules Pancrex V® capsules Pancrex V® Forte Tablets Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 13 of 14 Note: The CSM has advised of data associating the high-strength pancreatin preparations with the development of large bowel strictures in children with cystic fibrosis aged between 2 and 13 years and recommended that the total dose of pancreatic enzyme supplements used in patients with cystic fibrosis should not usually exceed 10,000 units of lipase per kg body-weight daily. It is important to ensure adequate hydration at all times in patients receiving higher strength pancreatin preparations. Additional NICE Guidance NG49 (Jul 2016): Non-alcoholic fatty liver disease (NAFLD): assessment and management NG50 (Jul 2016): Cirrhosis in over 16s: assessment and management CG141 (Aug 2016): Acute upper gastrointestinal bleeding in over 16s: management First line drugs Second line drugs Specialist drugs Specialist only drugs Adapted from Plymouth Area Joint Formulary and East Surrey Joint Formulary Chapter 1 Gastrointestinal System Page 14 of 14