Lansoprazole (Prevacid)

Prevacid® | Prevacid® Granules for Oral Suspension | Prevacid® IV | Prevacid® SoluTab™

Classification:
Gastrointestinal Agents

• Antiulcer Agents
  
  • Proton pump inhibitors (PPIs)

Description: Lansoprazole is an antiulcer drug similar to omeprazole. Like omeprazole, lansoprazole is an acid proton-pump inhibitor. It is used for the short-term treatment of duodenal or gastric ulcers, gastroesophageal reflux disease (GERD), and erosive esophagitis. It is also indicated to maintain healing of duodenal ulcer and esophagitis, for NSAID-induced ulcer treatment or prophylaxis, and for long-term treatment of Zollinger-Ellison syndrome (pathological hypersecretory condition). In vitro data indicate that lansoprazole is significantly more potent than either omeprazole or pantoprazole against H. pylori. Clinically, lansoprazole is at least as effective as omeprazole in treating peptic ulcers and reflux esophagitis, and it has been shown to relieve reflux symptoms more quickly than either omeprazole or ranitidine. Over a 4-week period, ulcer healing was greater with lansoprazole than ranitidine or placebo in a double-blind study of the treatment of active duodenal ulcer. A comparative study of omeprazole and lansoprazole in the short-term treatment of reflux esophagitis showed no significant difference in healing after 4 or 8 weeks. Lansoprazole, however, showed greater improvement in heartburn and acid regurgitation symptoms after 4 weeks. Lansoprazole has also been demonstrated to be safe and effective for chronic therapy of Zollinger-Ellison syndrome and for Barrett’s esophagus. Lansoprazole is also available in a therapy pack which contains clarithromycin and amoxicillin; this triple-drug regimen is indicated for the treatment of patients with duodenal ulcer and Helicobacter pylori infection. Lansoprazole was initially approved by the FDA May 10, 1995. A delayed-release oral suspension formulation of Prevacid® was approved by the FDA on May 3, 2001. Lansoprazole is approved for children >= 1 year and adolescents for short-term treatment of symptomatic GERD and erosive esophagitis. Prevacid® SoluTab™ Delayed-Release Orally Disintegrating Tablets were approved on August 30, 2002. All three oral Prevacid® dosage forms have delayed-release properties and contain lansoprazole within enteric-coated granules. An intravenous formulation of lansoprazole for the short-term treatment of erosive esophagitis was approved by the FDA on May 27, 2004. Oral Prevacid® is currently scheduled to go off patent by July 2005.

Mechanism of Action: Lansoprazole inhibits gastric acid secretion. It belongs to a new class of antisecretory agents, the substituted benzimidazoles, which suppress gastric acid secretion by inhibiting the H+/K+ ATPase enzyme system of gastric parietal cells. An acidic environment in the parietal cell is required for conversion of gastric-acid pump inhibitors, such as lansoprazole, to the active sulfenamide metabolite. The active metabolite then inhibits the ATPase enzyme required for gastric-acid pump activation, thereby blocking the final step of acid output from the parietal cells. A significant increase in gastric pH and decrease in basal acid output follow oral administration of lansoprazole. In hypersecretory conditions, lansoprazole has a marked effect on gastric acid secretion, both basal- and pentagastrin-stimulated. Lansoprazole exerts an inhibitory effect on gastric acid for at least 24 hours, which allows a once-daily dosing schedule. Lansoprazole does not antagonize H2 or cholinergic receptors.

Significant in vitro activity against Helicobacter pylori (H. Pylori) has been demonstrated for lansoprazole. Minimum inhibitory concentrations (MICs) for lansoprazole are lower than that for omeprazole. The clinical significance of this finding has not been established. Lansoprazole monotherapy increases the clearance rate of H. pylori; however, eradication does not occur without antimicrobial therapy.

Serum gastrin levels increase 50 - 100% from baseline in the fasting state, and these increases are greater during lansoprazole therapy than during ranitidine therapy. Increases reach a plateau within 2 months and return to pretreatment levels within 4 weeks of discontinuation of lansoprazole therapy. Although prolonged hypergastrinemia has been associated with gastric tumors, a long-term study of lansoprazole for the treatment of Zollinger-Ellison syndrome did not reveal evidence to suggest that lansoprazole was implicated in tumor progression noted in two (10% of) patients. Both patients already had extensive metastatic disease.

Short-term (i.e., 8-week) studies showed that lansoprazole had no effect on the endocrine system. Like omeprazole, however, lansoprazole also inhibits the hepatic cytochrome P450 oxidase system (see Drug Interactions).

Prevacid Delayed Release Capsules(Cap DR Pel 15 mg)

Pharmacokinetics: Lansoprazole is administered orally and should be taken in the morning at least 30 minutes before a meal on a once-daily schedule, unless large doses must be divided for hypersecretory conditions. All lansoprazole dosage forms (capsules, oral suspension, and disintegrating tablets) contain delayed-release, enteric-coated granules that release drug after they leave the stomach. Absorption of lansoprazole is rapid; mean peak plasma levels occur after about 1.7 hours. The absolute bioavailability is over 80%, which can be reduced by 50% if lansoprazole is given 30 minutes after food. Lansoprazole is about 97% bound to plasma protein. Lansoprazole is excreted into animal breast milk and possibly into human breast milk. Lansoprazole is believed to be transformed into two active inhibitors of acid secretion in the gastric parietal cells.

Hepatic metabolism of lansoprazole is extensive. The two identified hepatic metabolites of lansoprazole have little antisecretory activity. Plasma elimination half-life, which is less than 2 hours, is not related to gastric antisecretory effect, which lasts more than 24 hours. Elimination is believed to occur via biliary excretion. Almost no unchanged lansoprazole is detected in urine after single-dose administration. After administration of a single dose of radio-labeled lansoprazole, one-third of the administered radiation was excreted in urine and two-thirds in the feces.