PROTON PUMP INHIBITORS AN UPDATE

An initiative of NSW Clinical Pharmacologists & Pharmacists Funded by the NSW Department of Health

PROTON PUMP INHIBITORS AN UPDATE A Position Statement of the NSW Therapeutic Assessment Group Inc

December 1996

Dr Chris Liddle

Ms Lynn Weekes

This review was prepared by the authors in consultation with members of the NSW Therapeutic Assessment Group Inc.

EXECUTIVE SUMMARY

Omeprazole, the first proton pump inhibitor (PPI) marketed in Australia, has been followed by lansoprazole and pantoprazole. All are imidazole derivatives that decrease gastric acid secretion via inhibition of H + /K + ATPase.

Following review of the literature for the comparative efficacy and safety of the proton pump inhibitors available in Australia, NSW Therapeutic Assessment Group believe that the following conclusions are supported by the published evidence:

• The PPIs are effective agents for the treatment of peptic ulcer disease and gastro- oesophageal reflux disease (GORD). Advantages include dramatic inhibition of gastric acid secretion, long duration of action and a low incidence of adverse reactions. They are the agent of choice for the management of Zollinger-Ellison Syndrome.

• It is difficult to make firm recommendations at this time for the treatment of gastric and duodenal ulcer disease as optimal eradication strategies for H. pylori have yet to be identified. Both H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPI) are effective drugs for healing peptic ulcers. However, in uncomplicated ulcers, eradication of H. pylori infection, which will be present in the majority of cases, should be the prime aim of treatment. In this regard, a regime combining a PPI and antibiotics is attractive as it will rapidly relieve ulcer-associated pain, heal the ulcer and eradicate H. pylori. At present, there is no convincing evidence that H2RAs exert anti-H. pylori activity, giving omeprazole (and possibly the other PPIs - see below) a definite advantage in ulcer treatment strategies when H. pylori infection is known to be present.

• For mild GORD, H2RAs are of benefit and are sometimes combined with other agents such as prokinetic drugs. For more severe oesophagitis, or patients who fail to obtain symptom relief with H2RAs, PPIs are the medical treatment of choice.

• Clinical efficacy and safety data for peptic ulcer healing and management of GORD support the hypothesis that there are no significant differences between the three PPIs available in Australia. It seems reasonable, on existing data, to consider PPIs as class drugs with little in the way of important individual differences. For H. pylori eradication, most studies have used omeprazole with little data available for lansoprazole and pantoprazole. Further studies are required to confirm the efficacy of the latter two agents for this purpose.

Agency has withdrawn the marketing licence for the intravenous bolus formulation of omeprazole after 19 cases of impaired vision or transient blindness and 4 cases of impaired hearing were reported 80 . The intravenous preparation is approved for marketing in Australia for administration over 30 minutes. Serum gastrin levels rise during the first 3 months of long term omeprazole therapy but appear to plateau and were not observed to rise further despite treatment for more than 6 years 81 . Lansoprazole has a similar adverse event profile to omeprazole. It has most frequently been associated with headache (4.7%), diarrhoea (3.2%), abdominal pain (2.2%), pharyngitis (1.8%) and skin disorders (1.7%) 82 . Data concerning pantoprazole is limited, but adverse reactions are probably no different to omeprazole 83 . Early fears that PPIs may lead to carcinoid-like gastric tumours, as had been demonstrated in rats given prolonged high dose omeprazole 84 , have proven to be unfounded.

80. Schonhofer PS. Intravenous omeprazole and blindness. Lancet 1994; 343: 665. 81. Koop H, Arnold R. Long term maintenance treatment of reflux esophagitis with omeprazole. Dig Dis Sci 1991; 36: 552-7.

82. Colin-Jones DG. Safety of lansoprazole. Aliment Pharmacol Ther 1993; 7 (suppl 1) : 56-60.

83. Arnold R. Safety of proton pump inhibitors-an overview. Aliment Pharmacol Ther 1994; 8 (Suppl 1): 65-70.

84. Carlsson E, Larsson H, Mattson H, et al. Pharmacology and toxicology of omeprazole-with special reference to the effects on the gastric mucosa. Scand J Gastroenterol 1986; 21 (Suppl 118): 31.