Lansoprazole, Amoxicillin, and Clarithromycin (Prevpac—TAP)

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

Helicobacter pylori infection is associated with 90% of non-NSAID-related peptic ulcers. The bacterium, which commonly infects the upper GI tract, has also been implicated as a risk factor for gastric adenocarcinoma and low-grade gastric lymphoma of mucosa-associated lymphoid tissue.1 In January, the FDA approved TAP’s Prevpac, an administration pack containing one of the highly effective regimens for the eradication of H. pylori—the antibiotics clarithromycin and amoxicillin and a proton pump inhibitor, lansoprazole.

Indications

Prevpac is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease.

Dosage

Prevpac provides a daily dose of lansoprazole 30 mg (1 capsule), amoxicillin 1000 mg (2 capsules), and clarithromycin 500 mg (1 tablets) taken twice daily before meals (morning and evening) for 10 or 14 days.

Prevpac is supplied as a daily administration pack containing a sufficient number of capsules and tablets of the three-drug regimen.

Potential Advantages

Prevpac provides a highly effective and convenient regimen for the eradication of H. pylori. It is the only highly effective regimen in which all the components are available as a dispensing unit. This regimen also minimizes the risk of bacterial resistance since the rate of H. pylori resistance to either clarithromycin or amoxicillin is low, especially compared to metronidazole. A proton pump inhibitor-based triple-therapy regimen may be better tolerated with amoxicillin than with metronidazole.1 Dosing of this combination is convenient (twice daily) compared to the four times daily dose for bismuth subsalicylate, metronidazole, and tetracycline (e.g., Helidac). Compliance and side effects have been reported to be problematic with bismuth regimens.3

Potential Disadvantages

Prevpac should not be used in patients with penicillin allergy, these who are pregnant, or those who are receiving concomitant therapy with cisapride, astemizole, or pimozide.2 Potential drug interactions may occur between clarithromycin and ergotamine, triazolam, HMG-CoA reductase inhibitors, carbamazepine, cyclosporine, tacrolimus, phenytoin, disopyramide, alfentanil, bromocriptine, valproate, rifabutin, digoxin, protease inhibitors (e.g., ritonavir, indinavir), and warfarin.2 Lansoprazole may affect the absorption of ketoconazole, iron, and digoxin by reducing gastric acidity.2 Most common side effects reported with Prevpac are diarrhea (7%), headache (6%), and taste perversion (5%).2

Comments

Patients with peptic ulcers who have evidence of H. pylori infection benefit from eradication of the organism. Effective treatment promotes ulcer healing and reduces the rate of ulcer recurrence. Efficacious treatment regimens should have a cure rate of 90% and greater on per-protocol analysis and 80% or greater on intent-to-treat analysis.1 Prevpac has reported eradication rates of 81-86% on intent-to-treat analysis and 84-92% on per-protocol analysis.2 The intent-to-treat analysis is considered more reflective of clinical practice as this analysis includes patients who did not complete the treatment regimen for various reasons.7 A 10-day regimen appears to be as efficacious as a 14-day regimen.4 Lansoprazole also appears to be as efficacious as omeprazole.5

The cost of a 14-day treatment regimen with Prevpac is about $200. A combination of bismuth, metronidazole, and tetracycline (Helidac) with a proton pump inhibitor is about $170.

Clinical Implications

H. pylori infection is a common infection; however, most infected individuals are asymptomatic. Treatment is beneficial to those who have peptic ulcer disease or gastric mucosa-associated lymphoid tissue lymphoma.1 H. pylori eradication with one of the appropriate regimens should be first-line therapy for infected patients with peptic ulcer. The Guidelines for the Management of Helicobacter pylori Infection by the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology stated that the highest eradication rates are achieved with a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole for two weeks, ranitidine bismuth citrate, clarithromycin, and ether amoxicillin, metronidazole, or tetracycline for two weeks, or a proton pump inhibitor, bismuth, metronidazole, and tetracycline for 1-2 weeks.1 Diagnostic testing for H. pylori should only be performed if treatment is intended. There is no clear evidence that eradication of H. pylori will relieve symptoms of nonulcer dyspepsia.1 While H. pylori eradication significantly reduces ulcer recurrence, a recent meta-analysis indicated that 20% of patients had ulcer recurrence within six months. Laine and colleagues suggest that non-H. pylori or non-NSAID ulcers may be more common than previously believed.6 Prevpac is a regimen that is highly efficacious, convenient, and also minimizes the risk of developing bacterial resistance.

References

1. Howden CW, et al. Am J Gastroenterol 1998;93(12): 2330-2338.

2. Prevpac Product Information. January 1999. TAP Pharmaceuticals.

3. Dobrucali A, et al. Wien Med Wochenschr 1998; 148(20):464-468.

4. Fennerty MB, et al. Arch Intern Med 1998; 158(15):1651-1656.

5. Bazzoli F, et al. Helicobacter 1998(3):195-201.

6. Laine L, et al. Am J Gastroenterol 1998;93(9): 1409-1415.

7. William MP, et al. Drugs 1998;65(1):1-10.

Which of the following is not true about Prevpac?

a. The medications in the pack are given twice a day.

b. Bismuth in the product can cause black stools.

c. It is between 80 and 90% effective for treating H. pylori.

d. The rate of H pylori resistance to clarithromycin and amoxicillin is relatively low.