Reprinted from The Canadian Journal of Diagnosis Volume 23, Number 11 November 2006 Increasing Versatility of PPIs: The Place of Orally Disintegrating Lansoprazole © Copyright David Morgan, MD, FRCPC Dr. David Morgan Staff, Dr. Mark Atin St. Joseph’s Healthcare, Hamilton Associate Professor of Medicine, Dr. Guy Aumais Not for Sale of Commercial Distribution McMaster University Dr. Ronald Bridges Unauthorised use prohibited. Authorised use can download, Hamilton, Ontario display, view and print a single copy for personal use. Dr. Allan Cockeram Mark Atin, MD, FRCPC Staff Consultant, Dr. Flavio Habal University Health Network- Dr. Connie Switzer Toronto Western Hospital Site Toronto, Ontario Dr. Stephen Wolman Guy Aumais, MD, CSPQ, FRCP Staff, Maisonneuve-Rosemont Hospital Staff Teacher, University of Montreal Proton pump inhibitors (PPIs) have, since their introduction in the Montreal, Quebec 1990s, become integral and versatile agents in the therapeutic Ronald Bridges, MD, FRCPC armamentarium of general practitioners and specialists alike. Clinical Professor of Medicine, Currently available PPI compounds. The five compounds cur- University of Calgary Calgary, Alberta rently available in this class in Canada are esomeprazole (Nexium®), lansoprazole (Prevacid®), omeprazole (Losec® and Allan Cockeram, MD, FRCPC generics), pantoprazole (Pantoloc®) and rabeprazole (Pariet®). Staff Gastroenterologist, St Joseph’s Hospital Indications. PPIs are indicated for a broad range of conditions; Saint John Regional Hospital Facility however, the indications vary substantially from agent to agent.1-6 Clinical Associate Professor, For example, while all five agents are indicated for the treatment of Memorial University Dalhousie University gastroesophageal reflux disease (GERD), only lansoprazole, panto- Saint John, New Brunswick prazole and esomeprazole are indicated to prevent NSAID-associ- Flavio Habal, MD, PhD, FRCPC ated GU with ongoing NSAID therapy. All but rabeprazole are indi- Active Staff, cated for the healing of NSAID-associated gastric ulcers. Among University Health Network- the PPIs, lansoprazole has the broadest spectrum of indications; it Toronto General Site Associate Professor of Medicine, can be used to treat reflux esophagitis (including those cases asso- University of Toronto ciated with Barrett’s esophagus and those cases for whom histamine Toronto, Ontario H2-receptor antagonists are not currently effective), duodenal Connie Switzer, MD, FRCPC ulcers (DU), gastric ulcers (GU), NSAID-associated GU, and Active Staff, Zollinger-Ellison Syndrome. Lansoprazole is also the only agent Grey Nuns Community Hospital & Health Centre indicated for pediatric use (patients aged 1 to 17 years). All PPIs are Clinical Professor of Medicine, indicated for H. pylori eradication when given in association with University of Alberta antibiotic therapy. Edmonton, Alberta Available formulations. The available formulations of these Stephen Wolman, MD, FRCPC agents are shown in Table 1. For four of the six agents, the primary Staff, formulation is an oral tablet. Lansoprazole’s primary formulation is University Health Network- Toronto General Hospital Site an oral capsule containing active granules. The capsular formulation Assistant Professor of Medicine, of lansoprazole makes it more versatile than standard tablets. The University of Toronto, granules can be removed from the capsule and mixed into certain soft Toronto, Ontario foods (e.g., yogurt, apple sauce) or into selected beverages. They can also be flushed through a nasogastric tube. This has facilitated the use The Canadian Journal of Diagnosis / November 2006 101 TABLE 1 PPI Formulations Available in Canada Administration option includes Apo-omeprazole Esomeprazole Lansoprazole Omeprazole Pantoprazole Rabeprazole Capsule granules* ✓✓ Sprinkled on select soft ✓ food Mixed into select ✓ beverage Granules flushed through ✓ a nasogastric tube with apple juice Tablets ✓*** ✓† ✓** ✓ Disintegrating tablet ✓ (FasTab®) IV formulation ✓ (NOC) ✓ Adapted from the product monographs for apo-omeprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. *Do not crush or chew; **Do not split tablets; ***May be mixed into soft foods or dissolved in water and administered as a drink / be flushed through an NG tube; †Available formulations include multiple unit pellet system that can be dissolved in water and administered through an NG tube of PPIs in patients who have difficulty with oral and to the healthcare system in general. The medications (e.g., dysphagia, or difficulty swal- remainder of this review will focus on the use of lowing tablets/capsules). the orally disintegrating tablet for adult patients. Omeprazole is available in two oral formula- A subsequent specialist panel will discuss pedi- tions: regular capsules and the multiple unit pellet atric use of this formulation in more detail. system (MUPS), which can be dissolved in water and taken by mouth from a syringe or cup or LANSOPRAZOLE ORALLY flushed through a nasogastric tube. The generic DISINTEGRATING TABLET: OVERVIEW omeprazole is only available in capsules. Before discussing the particular characteristics of Esomeprazole tablets can also be dissolved into the orally disintegrating lansoprazole tablet, the water and the component pellets swallowed from panel briefly reviewed the efficacy and safety a cup or flushed through a nasogastric tube. records of the compound itself. For in-hospital use, lansoprazole and panto- Evidence with lansoprazole capsules. In prazole are approved by Health Canada as intra- clinical trials, lansoprazole has demonstrated a venous (i.v.) formulations. However, to date, rapid onset of action. Oral administration of lan- only pantoprazole i.v. is available in Canada, as soprazole capsules results in an increase of gastric the makers of lansoprazole i.v. have yet to mar- pH to greater than 4 within 130 minutes.7 This ket that formulation in this country. rapid onset of action has important clinical impli- The most recent addition to the list of PPI for- cations. In a comparative trial versus omeprazole mulations available in Canada is the lansopra- in erosive esophagitis, lansoprazole-treated zole orally disintegrating tablet (Prevacid patients were significantly less likely to experience FasTab®). daytime heartburn on the first day of therapy.8 In June of 2006, a group of specialists with an In placebo- or active-controlled, randomized interest in PPI therapy met to discuss the charac- studies, lansoprazole has proven to be effective teristics of the new orally disintegrating formula- in treating a number of different conditions, tion of lansoprazole and define the clinical set- including GERD,9 gastric ulcers,10 duodenal tings and patient types in which this formulation ulcers,11 functional dyspepsia,12 reflux symp- would be most beneficial. In the discussion of toms and esophagitis associated with Barrett’s each setting, the participants discussed the advan- esophagus,13 NSAID-associated GU14 and tage to the patient, to the healthcare professionals Zollinger-Ellison Syndrome.15 102 The Canadian Journal of Diagnosis / November 2006 Increasing Versatility of PPIs FIGURE 1 Bioequivalence of Lansoprazole Oral Capsule and Orally Disintegrating Tablet 800 700 600 Prevacid FasTab® 30 mg (n = 59) Prevacid® capsule 30 mg (n = 59) 500 400 300 200 100 Mean plasma concentration (ng/mL) 0 0123456789101112 Time (hours) Adapted from Freston JW et al. Aliment Pharmacol Ther 2003;17:361-7. In pediatric populations, lansoprazole has the orally disintegrating tablet demonstrate also been proven effective for GERD in chil- bioequivalence to the oral capsule. dren16,17 and adolescents.18,19 The flavoured In an open-label, crossover study of 120 oral suspension of lansoprazole has also been healthy subjects, lansoprazole administered as the associated with enhanced tolerability in chil- orally disintegrating tablet was bioequivalent to dren.20 The suspension is not, however, avail- the intact capsule formulation with respect to able in Canada. Cmax, AUCt and AUCinfinity (Figure 1).23 In In addition to its rapid onset of action and addition, direct oral administration of the orally effectiveness in treating various conditions in disintegrating tablet has been compared to disso- various populations, lansoprazole’s beneficial lution of that tablet in water. These two methods effects have also been shown in maintenance were also shown to be bioequivalent.24 therapy. Among patients who had been healed of Clinical-trial evidence. A recent publication erosive esophagitis, 79% of those treated with reported the results of two crossover trials com- maintenance lansoprazole (15 mg) remained paring various regimens of lansoprazole orally healed over one year, compared to only 24% of disintegrating tablet and i.v. lansoprazole vs. i.v. those in the placebo group.21 Lansoprazole has pantoprazole.25 The primary goal of treatment also been shown to be effective in maintenance was sustaining intragastric pH greater than 6.0. treatment of healed NSAID-related ulcers.22 The investigators of this relatively small proj- Clinical characteristics. The actual dissolu- ect found that while all the regimens resulted in tion time of the oral disintegrating tablet is usu- robust gastric acid suppression, lansoprazole ally less than 60 seconds.1 The tablet itself is regimens (including the orally disintegrating strawberry flavoured, which may enhance its tablet) were superior to the pantoprazole regi- acceptability.20 The tablet