Reviews for Primary Care - Fall 2007 - (Page 56) GERD Symptoms on Antisecretory Therapy continued his PPI is a rather obvious and straightforward choice. Another consideration would include changing the timing of the once-daily dose to before dinner. This would be based on intragastric pH data showing that overnight intragastric pH control is greater when once-daily PPI is given before the evening meal, compared to the morning.13 In my experience, this works only when nighttime symptoms are predominant but infrequent. There are no outcomes studies that have tested this option. Some would suggest a bedtime dose of PPI. This would not be logical with a delayedrelease PPI. The availability of omeprazole immediate release (non–enteric-coated granules protected by sodium bicarbonate) has made this choice more logical. The bicarbonate provides rapid control of intragastric pH early in the sleeping period with what appears to be sustained control throughout the night at steady state.14 Superior to pantoprazole in nighttime pH control in 1 published study,14 this product has recently been compared to esomeprazole and lansoprazole when each has been dosed at bedtime.15 The bedtime dose is superior to lansoprazole in onset of action and overnight control and faster in onset but similar to esomeprazole in number of hours of overnight pH control. Overall it is not clear if sufficient daytime control of pH will be provided with this formulation compared to esomeprazole when dosed at bedtime, and symptom studies have not been done. Nevertheless, a bedtime dose of omeprazole immediate release has inherent logic behind it. What is not clear is whether there is any overall gain from switching from one to another delayed-release PPI. If one looks at the available data, there is interindividual variability in pH control between PPIs, which provides foundation for a switch.16 If one looks Figure 1. Five-arm crossover study of intragastric pH control at steady state day 5, with proton pump inhibitors (PPIs) given once daily before breakfast. This pH control is sufficient to result in healing of 85% to 95% of patients with erosive esophagitis. Failure of complete symptom relief and/or healing may be explained by “incomplete” pH control. Adapted from Miner P et al,17 with permission from the American College of Gastroenterology. 14.0 12.1* 11.8† 11.5† 10.1† 0 5 10 Time (hr) pH * † P P .0010 .0001 20 15 4 Esomeprazole 40 mg Omeprazole 20 mg Pantoprazole 40 mg Rabeprazole 20 mg Lansoprazole 30 mg at individual pH responses to the 5 available delayed-release PPIs in a 5arm crossover study, esomeprazole 40 mg dosed once daily before breakfast was overall the most effective in 24hour pH control17 (Figure 1) and when compared with each PPI head to head was most often superior in individual control (Table 1).18 As such, if a switch in delayed release PPI was entertained, esomeprazole would be the logical second choice. The last intermediate step before doubling the dose would be to use an H2RA at bedtime. This has sound short-term logic19 and is less expensive than adding a sec- ond dose of PPI. One study, using intragastric pH as the intermediate marker, demonstrated short-term improvement in overnight pH control when an OTC dose of ranitidine (75 mg) was added at bedtime to omeprazole 20 mg before breakfast for 28 days.20 A study comparing omeprazole 20 mg plus ranitidine 150 mg at bedtime to omeprazole 20 mg twice daily favored the PPI twice daily for overall (including nocturnal) pH control.21 If an H2 is added at bedtime (HS) the clinician should expect some fall off in efficacy over time, even if successful initially. Table 1 Intrasubject Variability in Intragastric pH Control: Esomeprazole vs Other Proton Pump Inhibitors Favored Comparator (% of patients with a higher percentage of time pH 4.0) Esomeprazole (88) Esomeprazole (79) Esomeprazole (74) Esomeprazole (71) Comparison (n 34) Esomeprazole 40 mg vs pantoprazole 40 mg Esomeprazole 40 mg vs rabeprazole 20 mg Esomeprazole 40 mg vs omeprazole 20 mg Esomeprazole 40 mg vs lansoprazole 30 mg Adapted from Katz P et al.18 56 VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE
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