Pharmacology Update

Naproxen Tablets and Lansoprazole Capsules (PREVACID NapraPAC)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved the first combination NSAID and proton pump inhibitor (PPI). PREVACID NapraPAC is a combination package containing naproxen sodium and delayed-release lansoprazole. Individually, both drugs have been widely used for years.

Indications

Naproxen/lansoprazole is indicated for reducing the risk of NSAID-associated gastric ulcer in patients with a history of documented gastric ulcer who require the use of an NSAID for the treatment of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.1

Dosage

The recommended dose is based on the naproxen component, 375 mg or 500 mg twice daily. The recommended dose of lansoprazole is 15 mg daily. PREVACID NapraPAC is available as a 375 mg or 500 mg of naproxen with 15 mg of lansoprazole. The combination is supplied as a weekly blister card packaged as a 28-day supply. Each card contains 14 tablets of naproxen (375 mg or 500 mg) and 7 capsules of lansoprazole.

Potential Advantages

The package provides a convenient option for patients at risk for gastric ulcers and required co-administration of a NSAID and a PPI.

Potential Disadvantages

Lansoprazole is less effective than misoprostol in the prevention of NSAID-induced gastric ulcers.2 The fixed combination reduces the flexibility in NSAID or PPI selection, as well as dosing.

Comments

This is the first NSAID-PPI combination approved for use. This approval was supported by a large (n = 537) US, multicenter, double-blind, placebo- and misoprostol-controlled study. The patients required chronic use of an NSAID and had a history of endoscopically documented gastric ulcer. Those with a gastric or duodenal ulcer crater > 5 mm in diameter, severe erosions defined as > 25 erosions, or who were H pylori positive were excluded. Patients were randomized to placebo, lansoprazole 15 mg daily or 30 mg daily, or misoprostol 200 mg 4 times a day. At 12 weeks the percent of gastric ulcer-free patients were 51%, 80%, 83%, and 93% for placebo, lansoprazole 15 mg, 30 mg, and misoprostol, respectively. Misoprostol patients, however, experienced more side effects such as abdominal pain and had poorer adherence (73% vs 90%). In a post-hoc subgroup analysis involving only naproxen patients (n = 119), ulcer-free percentages were 33%, 89%, 83%, and 83%, respectively. In the populations studied, lansoprazole appears to significantly reduce the development of endoscopically detected ulcers. However, some patients (17%) still developed ulcers in 12 weeks. It has also been suggested that a PPI (omeprazole in this case) may provide an unrealistic sense of security in its effectiveness as prophylaxis against ulcer recurrence.3 While PREVACID NapraPAC provides a more convenient way of co-administration it does limit flexibility in NSAID selection or dosing and PPI choice. The daily wholesale cost for PREVACID NapraPAC is $3.74 per day compared to about $2.85 for generic versions of omeprazole and naproxen prescribed individually.

Clinical Implications

Suggested strategies for providing NSAID therapy in patients at risk for gastric ulcers include minimizing the dose of the NSAID, using less GI-toxic NSAIDs (ie, ibuprofen), co-administrations with misoprostol, co-administration with a PPI, using a COX-2 selective NSAID, or co-administration of a COX-2 inhibitor with a PPI.4,5 Normal doses of a histamine-2 receptor antagonist are not effective in reducing gastric ulcers and may mask warning symptoms of a more serious ulcer event.4 Double doses of H2RAs and standard dose PPI have been shown to be effective in reducing endoscopic gastric and duodenal ulcers.6 PREVACID NapraPAC provides a more convenient but more expensive option for co-administration of an NSAID with a PPI.

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are associate editors of Internal Medicine Alert.

References

1. PREVACID NapraPAC product information. TAP Pharmaceutical Product Inc. November 2003.

2. Graham DY et al. Arch Intern Med. 2002;162:169-175.

3. Graham DY. Helicobacter. 2002;7(1):1-8.

4. Hawkey CJ, Langman MJS. Gut. 2003;52:600-608.

5. Brown GJ, Yeomans ND. Drug Saf. 1999;21(6):503-512.

6. Rostom A et al. Cochrane Database Syst Rev. 2002;(4):CD002296.