Q.I.

D QUALITY INFORMATION on DRUGS

November 2000
Dunedin Medicines & Therapeutics Information Service, Pharmacy Department, Dunedin Hospital Telephone: 8876, 8886 (Internal), (03) 474 7658 (Direct), Facsimile (03) 474 7638

WISE USE OF PPIs

Introduction This bulletin provides recommendations on the appropriate use of proton pump inhibitors based on local expert opinion, and on the recent guidance produced by the National Institute for Clinical Excellence (NICE) in the UK (1) These recommendations will be expanded on in the Dyspepsia Guidelines soon to be published by the New Zealand Guidelines Group, and reflect the recent guidance issued to GPs by the Best Practice Advocacy Centre (BPAC).(2) We have consulted both groups to ensure our recommendations closely reflect their findings. The New Zealand Dyspepsia Guidelines will also discuss screening and diagnostic issues, which are outside the scope of this bulletin. Why the concern? In many countries, the prescribing of proton pump inhibitors (PPIs) has increased steeply over the past five years. In New Zealand as a whole, the prescribing volume has increased four-fold over the past two years. (2) In Dunedin Hospital, prescribing costs for these drugs have increased by 46% over the same period. ($31.8K to $46.4K). In the literature, there has been some debate over the safety of long-term use of PPIs. It seems timely, therefore, to consider the appropriate use of these agents. Safety issues? Concern about safety have arisen from a study showing a rise in plasma gastrin in patients on PPIs and another study showing bacterial overgrowth.(3)(4) In addition, a study by Kuipers in 1996 showed an annual increase in atrophic gastritis of 6.1% in Helicobacter Pylori positive patients (HP +ve) treated with omeprazole compared to 0.8% in HP ve patients. (5) Infected patients treated with fundoplication showed no increase in atrophic gastritis. This study, however, was non-randomised and patients treated with omeprazole were on average 9 years older than those in the fundoplication group. Since gastric atrophy from long lasting gastritis is thought to increase exponentially with age, t is not possible to draw definite conclusions from the study. A recent study by Lundell, however, has shown no difference in the incidence of atrophic gastritis when comparing HP +ve patients randomised to omeprazole or fundoplication.(6) Strategies for appropriate prescribing of PPIs A four-point strategy could be adopted for the prescribing of PPIs to reduce costs and reduce long-term exposure to the drugs. In addition to their use in Gastro-oesophageal Reflux Disease (GORD) and peptic ulcer, use should be considered in patients with previous peptic ulcer disease who must continue to take an NSAID. Recent studies support the use of omeprazole in this latter group and have shown a higher percentage of patients on omeprazole to be in remission from ulcers/gastric erosions after one year than patients on either misoprostol or ranitidine.(12)(13) The strategies could be: Ensuring patients are stepped-down from full-dose to half-dose of PPI after healing phase for GORD (Grades 0-2) or HP-ve peptic ulcers. (7)(8) Ensuring HP eradication regimens are given to patients with peptic ulcers who are HP +ve (9)(10)(11) Ensuring patients with a gastric or duodenal ulcer who must continue on an NSAID are given an acid suppressor, preferably a PPI or misoprostol. (12)(13) Adopting a step-up (or step-down) approach to therapy for Non-Ulcer Dyspepsia (NUD). Long-term prescribing of PPIs is not recommended and benefits have not been demonstrated in NUD. (1) Prokinetc agents may be more useful in patients with NUD e.g. domperidone (16)

DISEASE GORD

DIAGNOSIS
History or endoscopic evidence of heartburn

GRADE/ TYPE
Grade 0-2

TREATMENT
Treat symptoms with full-dose PPI and stepdown to half-dose or ranitidine 150mg bd (7)(8) Use full-dose to control symptoms(7)(8) Increase dose only if symptoms not controlled, then step-down and stay on full-dose (7)(8) 8-12 weeks full-dose PPI (14) Consider maintenance therapy if patient has complication/co- morbidity or frequent/severe recurrences. (PPI for gastric ulcer) 4-8 weeks full-dose PPI (14) Consider maintenance therapy as above. (H2RA for duodenal ulcer) Give Triple Therapy regimen for 7 days, to eradicate H Pylori e.g. one of standard regimens of a proton pump inhibitor and two antibiotics.(9)(10)(11) Give full-dose PPI bd, orally, for 1-2 weeks. Give by iv route if oral route contraindicated* (15) Prescribe an acid-supressor, preferably a PPI** or misoprostol (12)(13) After the ulcer has healed, step-down ,where possible, to the half-dose (1) Treat with a step-up or a step-down regimen. (1) PPIs are rarely necessary and should not be used long-term, if at all. (1) Prokinetic agents e.g. domperidone may be useful Patients with NUD may have symptoms caused by different aetiologies. (1) Patients should not be routinely treated with PPIs. (1) If symptoms appear to be acid-related, treat with an antacid or the lowest dose of an acid supressor to control symptoms. If symptoms are not acid related an alternative strategy should be employed. (1)

Grade 3-4

PEPTIC ULCER

Endoscopic diagnosis of a peptic ulcer

Gastric ulcer, HP-ve

Duodenal ulcer, HP-ve

Gastric or duodenal ulcer, HP+ve

Complications ie Gastric Bleeding

NSAIDINDUCED ULCERS NON-ULCER DYSPEPSIA

Endoscopic evidence of an NSAID-induced ulcer

Patients who must continue to be treated with an NSAID e.g. those with severe rheumatoid arthritis Mild dyspepsia

No endoscopic evidence of peptic ulcer or GORD

Moderate dyspepsia

NOTE Full dose PPI e.g. Omeprazole 20mg (Losec), Pantoprazole 40mg (Somac) Half dose PPI e.g. Omeprazole 10mg, Pantoprazole 20mg Manufacturers inform us there will be a global shortage of iv omeprazole until 12/2001. IV omeprazole is unobtainable in New Zealand at present (10/00). **Omeprazole and Lansoprazole are licensed for use in the prevention of gastric and duodenal ulcers in patients who must continue to take NSAIDs. REFERENCES 1. NICE. Guidance on the use of proton pump inhibitors in the treatment of dyspepsia. http//www.nice.org.uk 2. BPAC. Dyspepsia POEMS. September 2000. Best Practice Advisory Centre, Dunedin. 3. Lanzon-Millar S et al. Aliment Pharmacol.Ther 1987;1:239-51 4. Sharma BK et al. BMJ 1984; 289: 717-9 5. Kuipers EJ et al. N Eng J Med 1996; 334:1018-22 6. Lundell L et al. Gastroenterology 1999; 117(2):319-26 7. Moore RA and Phillips C. Bandolier 1997. http://www.jr2.ox.ac.uk/bandolier/bandopubs/gordf/gord.contents.htm 8. Bate CM et al. Gut 1995;36(4):492-8 9. Helicobacter Pylori and Peptic Ulcer, Effectiveness Matters 1 (2); University of York 1995 10. Penston JG and McColl KEC. J Clin Pharmacol 1997; 43: 223-43 11. Wermeille J et al. Pharmacy World and Science 1998; 20 (1): 1-17 12. Hawkey CJ et al. NEJM1998; 338;727-34 (OMNIUM study) 13. Yeomans N et al. NEJM1998;338;719-26 (ASTRONAUT study) 14. Data sheets- omeprazole (Losec),pantoprazole (Somac) and lansoprazole (Zoton). Medsafe web-site 15. Khuroo MS et al. N.Engl J Med 1997; 336(15):1054-8 16. Soo S et al. Cochrane Database of Systematic Reviews 2000; (2): CD001960 This bulletin was prepared by Professor Gil Barbezat (Gastroenterology) and June Tordoff (Drug Utilisation Pharmacist)