Lansoprazole

Abstract

Lansoprazole is a proton pump inhibitor that reduces gastric acid secretion. It has proved effective in combination regimens for the eradication of Helicobacter pylori and as monotherapy to heal and relieve symptoms of gastric or duodenal ulcers and gastro-oesophageal reflux. After initial healing, it may be used to prevent recurrence of oesophageal erosions or peptic ulcers in patients in whom H. pylori is not the major cause of ulceration and to reduce basal acid output in patients with Zollinger-Ellison syndrome. Usual dosages are 15 to 60 mg/day, although dosages of ≤ 180 mg/day have been used in patients with hypersecretory states. In patients with duodenal or gastric ulcer, short term lansoprazole monotherapy was similar to omeprazole and superior to histamine H₂ receptor antagonists in achieving healing rates >90%. Lansoprazole was as effective a component of H. pylori eradication regimens as omeprazole, tripotassium dicitrato bismuthate (colloidal bismuth subcitrate) or ranitidine. Lansoprazole was superior to ranitidine in symptom relief and healing of gastro-oesophageal reflux disease and tended to relieve symptoms more rapidly than omeprazole, although initial healing was similar. As maintenance treatment, lansoprazole was similar to omeprazole and superior to ranitidine in relieving symptoms and preventing relapse. Lansoprazole was also superior to ranitidine in healing and relieving symptoms of oesophageal erosions associated with Barrett’s oesophagus; healing was maintained for a mean of 2.9 years in ≥ 70% of patients. Lansoprazole was also superior to ranitidine in prophylaxis of redilatation of oesophageal strictures. After ≥ 4 years of use in patients with Zollinger-Ellison syndrome, lansoprazole 60 to 180 mg/day effectively controlled basal acid output. Dosages may be reduced in some patients once healing and symptom relief has been achieved. Preliminary studies of lansoprazole in patients at risk of aspiration pneumonia or stress ulcers show promise. Although studies show lansoprazole is potentially effective in treating gastrointestinal bleeding, future studies should assess patients’ H. pylori status. Lansoprazole has been well tolerated in clinical trials, with headache, diarrhoea, dizziness and nausea appearing to be the most common adverse effects. Tolerability of lansoprazole does not deteriorate with age and the drug is well tolerated in long term use (≤ 4 years) in patients with Zollinger-Ellison syndrome or reflux disease. Thus, lansoprazole is an important alternative to omeprazole and H₂ receptor antagonists in acid-related disorders. In addition to its efficacy in healing or maintenance treatment, it may provide more effective symptom relief than other comparator agents. Lansoprazole provides dose-related inhibition of gastric acid secretion via inhibition of H⁺/K⁺-adenosine triphosphatase in gastric parietal cells, with doses of 30 to 60mg producing similar acid suppression to omeprazole 40mg. Mean 24-hour gastric pH levels are higher when lansoprazole is given in 2 divided doses rather than 1 dose daily. Lansoprazole is 2 to 8 times more potent than omeprazole in inhibitory effects on H. pylori in vitro and is associated with dose-dependent killing of the bacterium. Orally administered lansoprazole is well absorbed, with peak plasma concentrations (C_max) linear over the dose range from 15 to 60mg. Sucralfate does reduce and food may reduce absorption of lansoprazole, and lansoprazole may reduce concentrations of theophylline. Both lansoprazole and the 14-hydroxy metabolite of clarithromycin are found in greater concentrations in plasma when administered together with amoxicillin. The drug is hepatically biotransformed and excreted through the bile and kidneys. The elimination half-life is ≈1 hour. Although clearance is reduced in poor metabolisers of S-mephenytoin, elderly patients and those with hepatic cirrhosis or undergoing haemodialysis, dosage adjustments are usually not considered except for patients with severe liver failure. For ease of administration, the enteric-coated granules in lansoprazole capsules may be mixed with apple sauce or juice before administration, with no major changes in pharmacokinetics. In peptic ulcer healing and symptom relief, lansoprazole 15 to 60 mg/day monotherapy for 4 to 8 weeks was similar or superior in efficacy to omeprazole 20 to 40 mg/day. Lansoprazole 30 mg/day was similar or superior to ranitidine and superior to famotidine in ulcer healing. When used in combination with ≥2 antibacterials, lansoprazole 30 to 60 mg/day was an effective part of regimens capable of achieving eradication of H. pylori in ≥90% of patients, although lansoprazole monotherapy was ineffective. The probability of achieving eradication in ≥90% of patients was highest in regimens incorporating ≥2 antibacterial agents and using ≤4 weeks of lansoprazole 60 mg/day. Healing rates seen in a subset of ≥1300 patients from these H. pylori eradication studies (receiving mono-, dual or triple therapy) were similar to those seen in earlier lansoprazole monotherapy trials. Healing was not affected by the number of agents in the regimen, the lansoprazole dosage or the ability of the regimen to eradicate H. pylori. As part of regimens with ≥2 antibacterial agents, lansoprazole 60 mg/day was as effective as omeprazole 40 mg/day, tripotassium dicitrato bismuthate 120mg 4 times daily or ranitidine 300 mg/day in H. pylori eradication and was similar to omeprazole and tripotassium dicitrato bismuthate but superior to cimetidine in achieving ulcer healing. As initial treatment of gastro-oesophageal reflux disease (GORD), lansoprazole 15 to 60 mg/day is superior to ranitidine 150mg twice daily in 2-week symptom relief and 4-week healing. Lansoprazole 30 mg/day and famotidine 40 mg/day for 4 weeks achieved...