Clinical audit: Review of proton pump inhibitor (PPI) prescribing Improving clinical practice for better patient health

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1 Clinical audit: Review of proton pump inhibitor (PPI) prescribing Improving clinical practice for better patient health How are you managing the use of PPIs? This clinical audit will assist you to review the management of your patients using PPIs, identify and implement a step-down strategy for suitable patients and review the concurrent use of drugs that may induce or exacerbate dyspepsia/ulceration. Identify 20 patients who are: using a proton pump inhibitor older than 16 years of age not pregnant not using a PPI as part of eradication therapy for Helicobacter pylori infection. This clinical audit activity has been approved by the RACGP QA&CPD Program, total points: 40 (Category 1), and by the ACRRM PD Program for 30 points (extended skills) in the triennium. Points are awarded only to participants who complete the review phase. This audit is recognised for the Quality Prescribing Initiative of the Practice Incentives Program (May 2009 to April 2010). Best practice in the prescribing of PPIs 1. Use best practice guidelines 5. Monitor progress Review the use of PPIs in all patients Review the need for ongoing use of PPIs. Discuss treatment expectations Ensure patients understanding of expected duration of treatment, symptom control and ongoing need. Identify patients suitable for step-down strategy Assess suitability for withdrawing or decreasing intensity of PPI therapy. Do I know why my patients are using a PPI? Have I reviewed how long the PPI has been used for? Are my patients receiving more than 8 weeks supply of PPI for initial treatment? Do any of my patients have alarm symptoms? Do I review the use of drugs that may induce or exacerbate dyspepsia/ulceration? Have I advised my patients on lifestyle modifications to minimise symptoms and reduce the need for PPIs? Do I outline treatment expectations when initiating a PPI? Have I discussed the potential rare but serious adverse drug effects of PPI use? How often are my patients using their PPI and at what dose? Do I routinely consider withdrawing PPI therapy? Do I routinely consider reducing the dose or decreasing the frequency of use of PPI therapy? 2. Review current practice Is symptom-driven therapy appropriate for any 4. Review and reflect of my patients? 3. Implement change Test and treat for Helicobacter Do I know the H. pylori status of my patients pylori infection with peptic ulcer disease? Successful eradication of H. pylori may reduce need for ongoing PPI use Have all my patients with H. pylori infection been offered eradication therapy? Guide

2 Notes for the clinical audit Additional information to assist you to review your management. Identify 20 patients prospectively as they present or retrospectively from a search of your medical records. Patients should be aware that your practice participates in quality assurance activities; display the poster Quality assurance in this practice and your privacy and make available the patient information leaflet Your health records and NPS clinical audits. Complete one double-sided audit form for each patient. Current Management Choice of PPI At equivalent doses all PPIs are clinically equivalent in most patients. 1 Differences in bioavailability between PPIs are not clinically significant. 2 Not all PPIs are funded by the Pharmaceutical Benefits scheme (PBS) for all indications. 3 Approved indications for each PPI differ. Refer to insert for comparative information on PPIs. Pantoprazole 20 mg is available as a Pharmacist Only medicine (Somac Heartburn Relief) for symptomatic relief of heartburn, acid regurgitation and other symptoms associated with gastro-oesophageal reflux disease (GORD). 4 Dosing schedule of PPI Exclude alarm symptoms and seek specialist advice if the continuous use of a PPI for > 8 weeks is ineffective. Doubling the dose of PPI has only small additional benefits in healing severe oesophagitis. 5 Table 1. Dose comparison of proton pump inhibitors PPI active ingredient Brand name esomeprazole Nexium lansoprazole Zoton omeprazole Acimax, Losec, Meprazol, Omepral, Probitor pantoprazole Somac rabeprazole Pariet Standard dose* Low dose* 20 mg daily 20 mg daily 30 mg daily 15 mg daily 20 mg daily 10 mg daily 40 mg daily 20 mg daily 20 mg daily 10 mg daily * Standard dose refers to the initial therapeutic trial dose used to provide symptom relief and heal erosive disease. 6 Low dose refers to the lower dose recommended for maintenance therapy for gastro-oesophageal reflux disease. 7 Esomeprazole 20 mg is recommended as the initial therapeutic trial dose to provide symptom relief and heal erosive disease. 6 Esomeprazole 40 mg daily is a PBS-listed restricted benefit for healing of gastro-oesophageal reflux disease, and may be appropriate if there is endoscopically proven erosive disease in a previously untreated patient. 6 HINT: Are your patients getting more prescriptions than they need for initial treatment? Be aware that electronically generated prescriptions may default to the maximum number of repeats. Patients may initially receive prescriptions for 6 months supply of PPIs. Manually select the minimum number of prescription repeats when prescribing to encourage return for review. Lifestyle modifications Lifestyle modifications are simple to advise on and implement as part of overall management, they also: offer additional general health benefits have limited effects in healing oesophagitis are adjunctive to appropriate drug therapy for patients with significant reflux disease should be encouraged in anyone with reflux symptoms. 5,8 Promote patient s awareness of diet Advise patients to avoid food and drinks that exacerbate their symptoms. Note that patients are unlikely to adhere to excessively restrictive diets. Encourage written records on episodes of dyspepsia and the foods or drinks consumed beforehand. Help patients identify dyspepsia-inducing foods or drinks, give examples: foods chocolate, fatty foods, spices drinks coffee and alcohol. Target behaviours that contribute to or reduce reflux Encourage: weight loss (if overweight or obese) 9 moderate alcohol consumption 10 quitting smoking 10 avoiding late large meals 5 avoiding reclining or lying down shortly after meals. 5 Support patient management of symptoms Advise patients on using symptom-driven PPI therapy. Provide information leaflets on self-management and step-down strategies. Go to 2

3 Adverse effects PPIs are generally well tolerated, but the incidence of rare but serious adverse effects increases in prevalence with increased and chronic use. Table 2. Rare but serious adverse effects Minimise adverse effects by: reviewing the need for ongoing maintenance PPI therapy prescribing the lowest effective dose of PPI for the shortest possible time. Acute interstitial nephritis Serious hypersensitivity reactions reported with all PPIs. 11 Symptoms are non-specific and onset may be delayed by as much as 12 months: weight loss fatigue malaise nausea and vomiting. 11,12 Renal function typically improves after withdrawal of the PPI, but there may be residual chronic kidney disease. 13 Clostridium difficile infection 2 3-fold increase in risk of Clostridium difficile infection in patients using a PPI. 14,15 Review PPI therapy in high risk patients e.g. patients using antibiotics, age 75 years or with renal failure. 14,16,17 Community-acquired pneumonia Increased rate of community-acquired pneumonia. 18,19 Hip fracture Associated with increased risk of hip fracture with higher doses and increased duration of therapy. 20,21 Helicobacter pylori infection H. pylori associated ulcer disease and gastro-oesophageal reflux disease often co-exist. 22 Stop PPIs at least 2 weeks before testing for H. pylori with a carbon-labelled urea breath test. 5 Offer eradication therapy if patients test positive to H. pylori infection. Consider the following patients for test and treat : uninvestigated dyspepsia investigated non-ulcer dyspepsia endoscopically confirmed peptic ulcer disease and H. pylori status unknown requiring long-term PPI therapy. 5,8,23 Endoscopy Endoscopic investigations often do not change management and are not for everyone. Most people with reflux symptoms have no endoscopic abnormalities. 8 Use endoscopy to investigate people with: alarm symptoms suggestive of malignancy, stricture or ulceration: (e.g. abdominal mass, anaemia, gastrointestinal bleeding, haematemesis, pain or difficulty on swallowing, unexplained weight loss) suspected complications symptoms refractory to initial PPI treatment unclear diagnosis (mixed, atypical or non-specific symptoms) need for reassurance when verbal reassurance is inadequate. 6,8 Table 3. The Los Angeles Classification System for the endoscopic assessment of reflux oesophagitis Grade A B C Appearance One or more mucosal breaks no longer than 5 mm, none of which extends between the tops of two mucosal folds. One or more mucosal breaks more than 5 mm long, none of which extends between the tops of two mucosal folds. One or more mucosal breaks which extend between the tops of two or more mucosal folds, but which involve less than 75% of the oesophageal circumference. D One or more mucosal breaks which involve at least 75% of the oesophageal circumference. 3

4 Drugs that may induce or exacerbate dyspepsia/ulceration Review concurrent drugs that may induce or exacerbate dyspepsia/ulceration. The following list is not exhaustive. Table 4. Main drugs or drug classes that may induce or exacerbate dyspepsia/ulceration 1,24,25 anticholinergic effect drugs (e.g. tricyclic antidepressants, antipsychotics, oxybutynin) beta blockers bisphosphonates (e.g. alendronate) calcium-channel blockers (e.g. verapamil) clopidogrel corticosteroids dopaminergic drugs (e.g. levodopa) iron nitrates (e.g. isosorbide mononitrate) NSAIDs conventional including aspirin and COX-2 selective slow-release potassium tetracyclines (e.g. doxycycline) theophylline These drugs may exacerbate dyspepsia by either relaxing the lower oesophageal pressure, or inducing symptoms of oesophagitis or dyspepsia. NSAID induced dyspepsia/ulceration Patients at high risk of NSAID induced dyspepsia/ulceration have two or more of the following: over 65 years past history of peptic ulcer disease serious gastrointestinal complications concomitant use of oral steroids or anticoagulants presence of serious co-morbidity (e.g. cardiovascular disease, renal or hepatic impairment, diabetes and hypertension or prolonged use of maximal doses of NSAIDs). 5,26 Discontinue the NSAID in patients who develop dyspepsia unless they are particularly necessary e.g. low-dose aspirin for cardiovascular protection. 5,8 If NSAID cannot be stopped then: Review every 6 months. 5 Use a COX-2 selective NSAID in preference to a conventional NSAID. 26 Use a conventional NSAID known to have a lower gastrointestinal risk e.g. diclofenac or ibuprofen in preference to higher risk agents e.g. piroxicam or ketoprofen. 26 Use the lowest dose of NSAID for the shortest time or use symptom-driven NSAID therapy. Use paracetamol in combination with an NSAID to reduce the NSAID dose required for osteoarthritis. Use a PPI prophylactically in high risk patients using an NSAID or aspirin. Review ongoing use of PPI therapy Duration of PPI therapy Review the need for ongoing PPI therapy when: there is a satisfactory response to an initial 4 8 week course of standard-dose of PPI therapy patients maintained on long-term PPI therapy present for repeat prescriptions a relapse of symptoms is successfully treated (using previously effective PPI therapy). 5,8 Trial PPI withdrawal in patients being treated empirically. Of these patients, 20% to 40% may not require another prescription in the following 6 12 months. 5,8 Consider a step-down strategy to PPI therapy (see Table 6 for types of step-down strategy). Continue long-term PPI use in patients with: severe oesophagitis Barrett s oesophagus Zollinger Ellison syndrome scleroderma or strictures prophylaxis of NSAID induced dyspepsia/ulceration. 5,6,8 4

5 Table 5. Duration of PPI therapy Clinical indication Recommended duration of PPI therapy Step-down strategy appropriate? Uninvestigated GORD/dyspepsia 4 8 weeks Determine ongoing need by a trial of withdrawal of PPI. 5,8 Yes Endoscopically-confirmed peptic ulcer disease Up to 8 weeks if confirmed H. pylori positive and successfully treated with eradication therapy weeks if confirmed H. pylori negative and not currently using NSAID/aspirin. 5 Investigated non-ulcer dyspepsia 4 8 weeks 5 Yes Endoscopy-negative reflux disease Yes 4 8 weeks 27 Yes Mild to moderate oesophagitis (Los Angeles Grades A and B) Severe oesophagitis (Los Angeles Grades C and D) Barrett s oesophagus, Zollinger Ellison syndrome, scleroderma, strictures Prophylaxis of NSAID induced dyspepsia/ulceration 4 8 weeks Determine ongoing need by a trial of withdrawal of PPI. 8 Continuous PPI therapy is indicated as relapse is likely. 8 Continuous standard or higher daily dose of PPI therapy is indicated. 1,5,6 Continuous PPI therapy. 5,26 See NSAID induced dyspepsia/ulceration Yes No No No Yes if NSAID treatment is stopped Step-down of PPI therapy Reduce the intensity of acid suppression once dyspeptic symptoms have been controlled. (See Table 5) Use a step-down strategy and monitor the response according to patient s dyspeptic symptoms. Emphasise to patients that a reduction in PPI therapy will still maintain symptom relief. Inform patients of the potential benefits of reducing PPI therapy: reduce prescription costs simplify medication regime reduce risk of adverse effects minimise drug interactions. Offer patients requiring long-term management of dyspepsia symptoms an annual review. 5 Table 6. Types of step-down strategy 1,5,8 Treatment withdrawal Trial a withdrawal of PPI therapy where indicated. (see Table 5) Some patients do not experience a clinically significant relapse of symptoms after withdrawal of effective initial therapy. Symptom-driven therapy Use the lowest effective dose of PPI on days when symptoms are troublesome. Some patients may prefer to: Use a PPI at the lowest effective daily dose as a fixed 2 4 week course. Reduced dose Use the lowest effective dose of PPI that maintains control of dyspeptic symptoms if continuous use is required. Alternatively a H 2 antagonist may be used. 75

6 Confidentiality and privacy You must sign and date the Submission cover sheet to participate in this audit. By participating you agree to aggregation of your de-identified patient data and use of your personal data. Individual results of your clinical audit are kept confidential by NPS. What will happen to your patient data Your de-identified patient data forms are scanned and returned to you. Your individual results are provided to you only. Your data are aggregated with those of other participants and the de-identified aggregate results: are provided to all participants may be used in NPS evaluation and reports are provided to the RACGP and ACRRM. The RACGP has advised that program information may be shared with researchers and interested general practitioners for the purpose of continuing education coordination at the discretion of the QA&CPD Program. What will happen to your personal details Your personal details: are provided to the mail house for processing are provided to the RACGP QA&CPD Program and/or ACRRM Professional Development Program for point allocation (if applicable) are recorded for the purpose of the PIP and NPS evaluation can be obtained from NPS by request in writing. Individual clinical audit results will not be available after potentially identifying data are removed from NPS records at the close of the clinical audit cycle. Please note: You are responsible for advising NPS of any changes of address during the audit cycle. Further information Therapeutic enquiries Nicole Fung-Coady (02) Audit and QPI enquiries Chun Fang Yu (02) References 1. Australian Medicines Handbook National Prescribing Centre. The management of dyspepsia in primary care. MeReC Briefing /dyspepsia_briefing_no_32.pdf (accessed 27 January 2009). 3. Australian Government Department of Health and Ageing. Schedule of Pharmaceutical Benefits Department of Health and Ageing, Therapeutic Goods Administration. Australian Register of Therapeutic Goods Public Summary : Somac Heartburn Relief pantoprazole (as sodium sesquihydrate) 20 mg tablet blister pack /ebs/anztpar/publicweb.nsf/cumedicines?openview (accessed 27 January 2009). 5. National Institute for Clinical Excellence. Dyspepsia: management of dyspepsia in adults in primary care. Clinical Guideline No /download.aspx?o=cg017niceguideline (accessed 20 January 2009). 6. Therapeutic Guidelines: Gastrointestinal. Version 4, Department of Veterans Affairs. PPIs in GORD: Reduce the dose - keep the benefits.therapeutic Brief 7. /veteransmates (accessed 13 January 2009). 8. Gastroenterological Society of Australia. Gastrooesophageal reflux disease in adults: guidelines for clinicians /RefluxDisease4Ed08.pdf (accessed 30 October 2008). 9. Hampel H, et al. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med 2005;143: Locke G, et al. Risk factors associated with symptoms of gastroesophageal reflux. Am J Med 1999;106: Sierra F, et al. Systematic review: Proton pump inhibitor-associated acute interstitial nephritis. Aliment Pharmacol Ther 2007;26: Geevasinga N, et al. Proton pump inhibitors and acute interstitial nephritis. Clin Gastroenterol Hepatol 2006;4: Brewster UC, Perazella MA. Proton pump inhibitors and the kidney: critical review. Clin Nephrol 2007;68: Dial S, et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA 2005;294: Leonard J, et al. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol 2007;102: Dial S, et al. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ 2004;171: Muto CA, et al. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol 2005;26: Laheij R, et al. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA 2004;292: Gulmez S, et al. Use of proton-pump inhibitors and the risk of community-acquired pneumonia: a population-based case-control study. Arch Intern Med 2007;167: Yang YX, et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 2006;296: Targownik LE, et al. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ 2008;179: Gastroenterological Society of Australia. Gastro-oesophageal reflux disease in adults: guidelines for clinicians au/members_guidelines/goreflux /index.htm (accessed 24 April 2006). 23. Malfertheiner P, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Concensus Report. Gut 2007;56: Gowan J. Dyspepsia - a primary care issue? Australian Pharmacist. 2008;27: Meyler s side effects of drugs. Amsterdam: Elservier, Gastroenterological Society of Australia. NSAIDs and the Gastrointestinal Tract /GesaNSAIDSClinical.pdf (acessed 10 February 2009). 27. Dyspepsia-proven GORD. Clinical Knowledge Summaries /dyspepsia_proven_gord (accessed 10 February 2009). April 2009 The information contained in this material is derived from a critical analysis of a wide range of authoritative evidence. Any treatment decisions based on this information should be made in the context of the clinical circumstances of each patient. NPSA0878 National Prescribing Service Limited ACN An independent, non-profit organisation for Quality Use of Medicines, funded by the Australian Government Department of Health and Ageing. Level 7 / 418A Elizabeth Street Surry Hills NSW 2010 Phone: l Fax: l info@nps.org.au l web:

7 Comparative information for oral proton pump inhibitors 1,2 Key: Indications Indicated for use Not indicated Not an approved indication but an accepted indication due to evidence of efficacy. Peptic ulcers (initially 4 8 weeks treatment) GORD initially maintenance Esomeprazole* (Nexium) tablet (Gastric ulcers, initially 20 mg/day ) mg/day Reduce to minimum dose required 20 mg* Lansoprazole (Zoton) capsule, granules for suspension Initially 30 mg/day then mg/day 30 mg once or twice/day Reduce to minimum dose required 15 mg PBS Seek specialist advice PBS PBS Restricted Benefit (as at February 2009) Note: Use of PPI for indications other than restricted benefits on the PBS should be by private prescription. Omeprazole (Acimax, Losec, Meprazol, Omepral, Probitor) tablet, capsule Initially mg/day then mg/day mg/day Reduce to minimum dose required 10 mg Pantoprazole (Somac) tablet Initially 40 mg/day mg once or twice/day (max 80 mg/day) Reduce to minimum dose required 20 mg Rabeprazole (Pariet) tablet Initially 20 mg/day mg once or twice/day Reduce to minimum dose required 10 mg lowest dose available PBS PBS PBS PBS Scleroderma oesophagus Seek specialist Seek specialist Seek specialist advice advice advice PBS PBS PBS PBS Zollinger Ellison syndrome Up to 240mg/day Up to 120 mg/day Up to 240 mg/day Treatment and prophylaxis of ulcers and erosion associated with NSAID use Treatment: 20 mg/day, 4 8 weeks (gastric ulcer) Symptom control: 20 mg/day, 4 weeks Prophylaxis: 20 mg/day (peptic ulcer) PBS PBS PBS PBS PBS Treatment: mg/day 4 8 weeks Prophylaxis: 20 mg/day PBS Prophylaxis: 20 mg/day PBS Helicobacter pylori eradication (in combination with dual antibiotic therapy for 1 week) Dose frequency 20 mg twice daily 30 mg twice daily 40 mg daily or 20 mg twice daily PBS Once daily, swallowed whole. Tablet may be dispersed in non-carbonated water only and taken within 30 minutes. Do not chew or crush. Capsules: Once or twice daily. In the morning before food. Swallow capsule whole; do not crush or chew. May be dispersed in apple, orange, or tomato juice, yoghurt or apple sauce and taken immediately. Granules: add to 30 ml of water, stir well and drink immediately. Give doses > 120 mg/day as 2 divided doses. PBS Once or twice daily, swallowed whole. Tablet may be dispersed (not broken or crushed) in non-carbonated water or fruit juice and taken within 30 minutes. Give doses > 80 mg/day as 2 divided doses. 40 mg twice daily 20 mg twice daily Once or twice daily. Swallow tablet whole; do not crush or chew. May be taken with or without food. Give doses > 160 mg/day as 2 divided doses. Once or twice daily. Swallow tablet whole; do not crush or chew. May be taken with or without food. * Esomeprazole is available as 10 mg granules for oral suspension in paediatric doses. NPS is an independent, non-profit organisation for Quality Use of Medicines, funded by the Australian Government Department of Health and Ageing. National Prescribing Service Limited ABN l Level 7/418A Elizabeth Street Surry Hills NSW 2010 l PO Box 1147 Strawberry Hills NSW 2012 Phone: l Fax: l info@nps.org.au l web:

8 Interactions with PPIs (including suspected and possible interactions) 3,4 PPIs Esomeprazole (Nexium) Lansoprazole (Zoton) Omeprazole (Acimax, Losec, Meprazol, Omepral, Probitor) Pantoprazole (Somac) Rabeprazole (Pariet) Interacting drugs (This is not an exhaustive list. See table below for mechanism of interaction and management options.) citalopram, clarithromycin, clopidogrel, diazepam, erythromycin clarithromycin, clopidogrel, erythromycin, methotrexate, theophylline clarithromycin, clopidogrel, clozapine, diazepam, erythromycin, methotrexate, phenytoin methotrexate clopidogrel, digoxin Antiretrovirals: delavirdine and protease inhibitors (e.g. atazanavir, indinavir) Azole antifungals: ketoconazole, itraconazole (capsule only) Ginko biloba, St John s wort Warfarin (isolated cases of raised INR reported with all PPIs) People who are known to be poor metabolisers of CYP2C19 (1% to 6% of Caucasians, 1% to 7.5% of Blacks and 12% to 23% of Oriental and Indian Asians) are more dependent on CYP3A4 for the metabolism of PPIs. PPI level may be raised in patients concurrently using CYP3A4 inhibitors (e.g. clarithromycin). Selected interacting drugs Pharmacokinetic effects Management Azole antifungals: ketoconazole, itraconazole (capsule only) clopidogrel 5,6 clozapine Complementary medicines: Ginko biloba, St John s wort diazepam Macrolides: clarithromycin erythromycin methotrexate phenytoin Protease inhibitors: e.g. atazanavir, indinavir warfarin Decreased absorption of some antifungals due to the increase in gastric ph. Decreased levels of azole antifungals. Decreased metabolism of clopidogrel pro-drug (limited data). Decreased activity of clopidogrel (possible). Increased metabolism of clozapine (suspected mechanism). Decreased levels of clozapine (possible). Increased metabolism of PPIs. Decreased levels of PPIs Decreased metabolism of diazepam. Increased levels of diazepam. Decreased metabolism of PPIs. Increased levels of PPIs. Decreased renal and (possible) hepatic clearance of methotrexate. Increased levels of methotrexate. Decreased metabolism of phenytoin. Increased levels of phenytoin. Decreased absorption of some protease inhibitors due to the increase in gastric ph. Decreased levels of protease inhibitors. Decreased metabolism of warfarin. Increased INR (possible). Avoid combination when possible. Give ketoconazole or itraconazole with an acidic drink (e.g. a cola beverage) to minimise the interaction. Be aware of the potential for reduced efficacy of clopidogrel. Review ongoing need for PPI therapy. Available data suggests no special precautions necessary for pantoprazole. Monitor clinical response, dosage adjustment may be necessary. Be aware of the potential for reduced efficacy of PPI therapy. Consider avoiding combination especially when consequences may be serious (eg. patients with healing ulcers). Advise patient of potential interaction. Monitor patient for increased benzodiazepine effects (sedation, unstable gait, etc). Reduce dose of benzodiazepine if necessary. No special management considerations. Interaction may be valuable in H. pylori eradication regimens. No special precautions necessary for roxithromycin, unlikely to interact. Consider an alternative to PPI (e.g. H 2 antagonist) when using high dose methotrexate for chemotherapy. If PPI treatment necessary: Discontinue PPI therapy 4 5 days before high dose methotrexate. Monitor methotrexate concentration carefully. Increase rescue treatment with calcium folinate if needed. Monitor plasma phenytoin level especially when higher doses of PPIs are used i.e. omeprazole 20 mg did not affect plasma phenytoin level, whereas 40 mg caused slight increase. No special precautions necessary for rabeprazole or pantoprazole. Avoid combination. Monitor INR. References 1. Australian Government Department of Health and Ageing. Schedule of Pharmaceutical Benefits Therapeutic Guidelines: Gastrointestinal. Version 4, Australian Medicines Handbook, Baxter K, ed. Stockley s Drug Interactions, 8th Edition. London: Pharmaceutical Press, Juurlink DN, et al. CMAJ 2009 doi: /cmaj Ho PM, et al. JAMA 2009;301:

9 Clinical audit: Review of proton pump inhibitor (PPI) prescribing Your patient code: Do not use patient name. Use this to identify your patients for the Review Phase. Patient details Use a black biro to mark a cross (X) in the box beside your response. If you make a mistake, use white correction fluid. NPS office use only 1. Age range: 16 years 54 years 55 years 2. Gender: male female Current management 3. Which PPI is the patient using? active ingredient (Brand name) 6. Who initiated/recommended the current PPI? myself other medical specialist pharmacist/patient another GP following hospital stay not known 7. When was PPI treatment last reviewed? < 4 weeks 4 8 weeks > 8 weeks 12 months > 12 months not known 8. Has the dosage of PPI been changed during the current course of treatment? yes no not known increased decreased both increased and decreased Indication for current treatment 4. What is the current DAILY dose of PPI? e.g. omeprazole 20 mg twice a day = 40 mg/day esomeprazole (Nexium) 20 mg/day 40 mg/day other lansoprazole (Zoton) 15 mg/day 30 mg/day 60 mg/day other omeprazole (Acimax, Losec, Meprazol, Omepral, Probitor) 10 mg/day 20 mg/day 40 mg/day other pantoprazole (Somac) 20 mg/day 40 mg/day 80 mg/day other rabeprazole (Pariet) 10 mg/day 20 mg/day 40 mg/day other 14. What is the clinical indication(s) for treatment with a PPI? (Mark all that apply) 5. What is the dosing schedule of PPI? Regularly each day Symptom driven 9. Has lifestyle modification been advised? (See Guide page 2) yes no not known 10. What is the H. pylori status of this patient? positive negative not known 11. Has this patient had H. pylori eradication therapy? yes no not known 12. Have potential rare but serious adverse drug effects of PPI use been discussed with the patient? (See Guide page 3) yes no not known 13. Is the patient using medication(s) that may induce or exacerbate dyspepsia/ulceration? (See Guide page 4) yes no not known SAMPLE Not known endoscopically confirmed GORD ( specify) mild to moderate oesophagitis (Los Angeles Grades A and B) severe oesophagitis (Los Angeles Grades C and D) prophylaxis of drug-induced dyspepsia/ulceration ( specify) aspirin conventional NSAID COX-2 selective NSAID other uninvestigated GORD/dyspepsia ( specify) mild to moderate symptoms severe symptoms Barrett s oesophagus If you marked any strictures, scleroderma pink boxes long-term PPI use Zollinger Ellison syndrome is required. Have you reviewed the drug(s) for: Risk/benefit yes no Continued need yes no Recommended dose yes no Alternative drug options yes no endoscopy-negative reflux disease endoscopically confirmed peptic ulcer disease ( specify) H. pylori induced ulcer disease NSAID induced ulcer disease unknown cause of ulcer disease investigated non-ulcer dyspepsia uncertain diagnosis other If you marked: prophylaxis of drug-induced dyspepsia/ulceration. No need to complete Q15 & Q16. Please turn over to complete form

10 Review maintenance use (> 8 weeks) of PPI therapy 15. How long has the patient been using a PPI? < 4 weeks 4 8 weeks > 8 weeks 6 months > 6 months not known Planned action Review use at 8 weeks STOP HERE! 16. Review maintenance use of PPI: step-down strategy Continue to Q16 Does the patient have: alarm symptoms: abdominal mass, anaemia, GI bleeds, haematemesis, pain or difficulty on swallowing, unexplained weight loss unclear diagnosis persistent refractory symptoms suspected or previous complications need for reassurance when verbal reassurance is inadequate 1 or more marked Continue here None marked Continue here Has the patient had an endoscopy for this course of treatment? no REFER FOR ENDOSCOPY and specialist management STOP HERE! Which of the following were tried? (Mark all that apply) confirmed adherence referred for endoscopy and/or specialist management increased dose of PPI test and treat continued current management for H. pylori infection other Planned action Major pathology (Barrett s oesophagus, strictures, scleroderma, severe oesophagitis, Zollinger Ellison syndrome, malignancy) Continue specialist management STOP HERE! Planned action Consider step-down strategy when adequate control of symptoms trial withdrawal of PPI reduce dose of PPI switch to symptom-driven use of PPI switch to daily or symptom-driven use of H 2 antagonist continue current management (give details) yes OR No major pathology Has this patient achieved adequate control of symptoms? no yes SAMPLE Has this patient tried step-down strategy during this current treatment? no yes Which step-down strategies were used? (Mark all that apply) trialled withdrawal of PPI reduced dose of PPI switched to symptom-driven use of PPI switched to daily or symptom-driven use of H 2 antagonist Was it successful? no yes Document any planned actions in the Action plan for individual patients and/or the patient s file to assist with implementing changes to practice. Planned action re-try step-down strategy maintain on current dose of PPI refer for endoscopy test and treat for H. pylori infection NPSA0878

11 Review of proton pump inhibitor (PPI) prescribing Enrol by Friday 12 June 2009 Fill out the form below then return to NPS. Fax this form to: OR Telephone: OR Post to: PO Box 1147 Strawberry Hills NSW 2012 For more information To see a sample audit form before enrolling or enrol online, visit Nicole Fung-Coady Phone: Chun Fang Yu { info@nps.org.au Your free audit pack will be forwarded by mail. Submit initial data collection by Friday 10 July 2009, for completion of the clinical audit by February See over for more details Participant details GP GP registrar Other medical specialist (please mark relevant box) Please use BLOCK LETTERS Title Dr Mr Mrs Miss Ms Family name Given name Postal address Town or Suburb State or Territory Postcode Phone no. Fax no. Prescriber no. Provider no. NPS consults widely with general practitioners in the development of quality assurance activities. Yes, I am interested in participating in the development of NPS quality assurance activities. NPS adheres to the National Privacy Principles contained in the Privacy Act 1988 (Cwth). All personal information collected by NPS will be used only for mailing of NPS materials relating to this audit and/or evaluation purposes. NPS is an independent, non-profit organisation for Quality Use of Medicines, funded by the Australian Government Department of Health and Ageing. National Prescribing Service Limited ABN l Level 7/418A Elizabeth Street Surry Hills NSW 2010 l PO Box 1147 Strawberry Hills NSW 2012 Phone: l Fax: l info@nps.org.au l web: NPSF0923