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all-cause mortality.2,4,5 Long-term regular use of PPIs is recommended for only a limited number of indications and should be accompanied by regular review of PPI therapy.2 Despite this, reports from the BEACH program indicate the average duration of PPI therapy in Australia is considered long-term, on average 3.8 years.6 A review of all PBS-listed medicines for GORD by the Drug Utilisation Sub Committee found high-dose PPIs (eg, esomeprazole 40mg) appear to be overprescribed in Australia, for excessively long periods of time, particularly among older people.7 Ninety-five per cent of PPI prescriptions dispensed were for high and highest-dose PPIs, while only five per cent were for low- dose PPIs.7 This pattern of overprescribing raises safety concerns for patients and contributes to the high PBS expenditure on PPIs.7 In response, access to PPIs on the PBS has been restricted, with additional administrative processes, including authority requirements for high-dose PPIs and streamlined authority for standard- dose PPIs, put in place as of May 2019.7 Tapering and stepping off PPIs A challenge with trialling taper of PPI dose is rebound symptoms, which may occur due to acid hypersecretion.8 This is a potential barrier to patients stepping down off their PPI and may contribute to them taking PPIs long term without an indication. Studies have demonstrated that patient education alone doesn’t appear to be enough to reduce PPI use.9,10 An on-demand strategy to help patients cope with breakthrough symptoms during PPI tapering is required, and pharmacists have an important role to play in advising on this strategy as it can involve the use of OTC options. While algorithms exist that note OTC medications can be used to help manage occasional symptoms, current guidelines don’t distinguish between the roles of OTC treatments to manage mild or intermittent GORD symptoms.3 On-demand therapy using less potent drugs such as antacids, alginates, H2RA, or standard-dose PPIs available OTC may be viable alternatives to high-dose PPIs.2 Better understanding of the role of OTC treatments is needed to assist tapering of PPI therapy. However, one study found only 25 per cent of GPs would recommend an add-on therapy with a different mechanism of action if a patient experiences ongoing PPI treatment failure, while only 52 per cent of gastroenterologists shared the same point of view.11 Understanding the utility of Table 1. Evidence for comparing OTC treatments for GORD. CPD ACTIVITY 51 Comparison Evidence Antacid versus alginate Meta-analysis of 9 randomised controlled trials favours alginates versus antacids or placebo; OR 4.42 (95% CI 2.45- 7.97; p=0.001) (14). Antacid versus H2RA or PPI No direct comparisons. Alginate versus H2RA or PPI Meta-analysis of 5 randomised controlled trials favours H2RAs or PPIs; OR 0.58 (95% CI 0.27-1.22) (14). OTC treatments in assisting PPI taper could help ease the pressure on PPI prescribing. A review of the literature was performed using the following terms in the PubMed database: antacid, alginate, reflux, heartburn, GORD, GERD, proton-pump inhibitor, step-down therapy. The search was limited to studies involving human subjects published in English conducted until July 31, 2019. OTC treatments for mild to moderate GORD symptoms Antacids, alginates, H2RAs and PPIs are available OTC for the management of mild to moderate GORD. Table 1 summarises the key attributes and relative evidence. Antacids mix with stomach contents and rapidly neutralise hydrochloric acid on contact. This has the effect of reducing irritation of the oesophagus when stomach contents are regurgitated.12,13 However, their effect is short-lived and repeated dosing may be required as acid continues to be produced as the antacid passes from the stomach16. In a fasting patient the antacid can persist for about 20 minutes, while if taken after a meal, may remain in the stomach for up to 60 minutes.13 Alginate-based therapies function differently to antacids, PPIs and H2RAs. Rather than interfering with stomach acid, they limit exposure of the oesophagus to acid reflux. A low-pH acid pocket forms in the proximal region of the stomach after eating and accumulates above the stomach contents without mixing.14,15 Alginate rafts (in the form of a viscous gel) form a buffer between the acid pocket and the oesophagogastric junction.12,13,16,17 There is evidence that alginates may also modulate other GORD factors such as pepsin.17,18 Like antacids, alginates demonstrate a fast onset of action, faster than PPIs and H2RAs.2 A systematic review and meta-analysis of nine randomised, controlled trials found a significant treatment benefit for alginates over placebo or antacids (odds ratio 4.42, 95 per cent confidence interval 2.45,7.97).19 H2RAs generally provide a longer period of relief than antacids or alginates, typically maintaining intragastric pH elevation for at least six hours.13 A systematic review and meta-analysis of five studies showed H2RAs and PPIs tended to be more effective than alginates in resolving symptoms of GORD, though statistical significance was not reached.19 H2RAs are less effective than PPIs at standard doses.2 While most GORD patients taking H2RAs show improvements in their symptoms, in general they are not as effective as PPIs in acid suppression.20 In Australia, low-dose PPIs are available OTC for a maximum of 14 days. PPIs bind to active proton pumps to inhibit the final common step in three different pathways that contribute to acid secretion.21 About 70-80 per cent of proton pumps are active after a meal, while 20-30 per cent of proton pumps are inactive and will need to be inhibited by further PPI doses.21 Hence it takes about three to four days after the first PPI dose before the maximum effect of PPIs are observed.21 Although the onset of action for PPIs is longer compared with antacids and H2RAs, these are the most potent acid suppressants available to date.21 Yet around one-third of patients taking PPIs experience breakthrough symptoms.22,23 Evidence of OTC reflux treatments in supporting breakthrough symptoms for patients taking or tapering the dose of PPIs When GORD symptoms aren’t adequately controlled, add-on therapy with antacids, alginate-antacid combinations, or H2RAs may be used.2 A benefit of both antacids and alginates may be their different mode of action from PPIs and H2RAs. However, for antacids there is limited evidence to support their role as an add-on treatment for PPI breakthrough symptoms.24 There is a growing body of evidence for alginate-based treatments to reduce breakthrough symptoms when used alongside PPIs.25 This may be due to the ability of alginates to co-localise with the acid pocket, which can persist in patients taking PPIs.27 Yet there remains reluctance to consider alginate therapy as an add- on therapy to PPIs. In one study, 93.5 per cent of GPs reflected that despite PPI monotherapy, some of their patients with GORD would remain symptomatic TO PAGE 52 RETAIL PHARMACY • AUG 2020