Anti-Helicobacter Pylori Drugs

ANTI-HELICOBACTER PYLORI DRUGS

H. pylori is a gram negative bacillus uniquely adapted to survival in the hostile environment of stomach. It attaches to the surface epithelium beneath the mucus, has high urease activity— produces ammonia which maintains a neutral microenvironment around the bacteria, and promotes back diffusion of H+ ions. It has been found as a commensal in 20–70% normal individuals, and is now accepted as an important contributor to the causation of chronic gastritis, dyspepsia, peptic ulcer, gastric lymphoma and gastric carcinoma. H. pylori infection starts with a neutrophilic gastritis lasting 7–10 days which is usually asymptomatic. Once established, H. pylori generally persists for the life of the host. Up to 90% patients of duodenal and gastric ulcer have tested positive for H. pylori.

Eradication of H. pylori concurrently with H₂ blocker/PPI therapy of peptic ulcer has been associated with faster ulcer healing and markedly lower relapse rate. Anti-H. pylori therapy is, therefore, now recommended in all ulcer patients who test positive for H. pylori. In the absence of such testing, all cases with failed conventional ulcer therapy and relapse cases may be given the benefit of H. pylori eradication.

Antimicrobials that have been found clinically effective against H. pylori are: amoxicillin, clarithromycin, tetracycline and metronidazole/ tinidazole. However, any single drug is relatively ineffective. Resistance develops rapidly, especially to metronidazole/tinidazole. Since bismuth (CBS) is active against H. pylori and resistance does not develop to it, early combination regimens included bismuth, but had poor patient acceptability; are infrequently used now. In the meantime, it was observed that omeprazole monotherapy reduces the population of H. pylori in gastric antrum, probably by altering the acid environment as well as direct inhibitory effect. Rise in intragastric pH enhances the antiH. pylori action of the antibiotics. A number of 2drug and 3drug regimens of 1 or 2 weeks duration have been tested reporting 60– 96% eradication rates, but the optimum regimen is difficult to proclaim. Some of the 2 week regimens are:

Two Week Regimens (mg)m

g

1.     Amoxicillin 750 + Tinidazole 500 + Omeprazole 20 all BD

2.     Amoxicillin 750 + Tinidazole 500 + Lansoprazole 30 all BD

3.     Clarithromycin 250 + Tinidazole 500 + Lansoprazole 30 all BD

4.     Clarithromycin 500 + Amoxicillin 1000 + Lansoprazole 30 all BD

5.     Clarithromycin  500  BD/Amoxicillin 750 BD + Omeprazole 20 BD

6.     Amoxicillin  500  TDS/Tetracycline 500 QID + Metronidazole 400 QID/ Tinidazole 500 BD + Bismuth 120 QID

7.     Amoxicillin 750 TDS + Metronidazole 500 TDS + Ranitidine 300 OD

8.     Amoxicillin 750 BD + Clarithromycin 250 BD + Lansoprazole 30 BD

The US-FDA approved regimen is: lansoprazole 30 mg + amoxicillin 1000 mg + clarithromycin 500 mg all given twice daily for 2 weeks. It has achieved 86–92% eradication rate.* High prevalence of in vitro nitroimidazole resistance among H. pylori now being detected, especially in tropical regions, and better tolerability of regimens which exclude the nitroimidazole, favour the triple drug regimen of a PPI + amoxicillin + clarithromycin. The 2 week treatment is considered more appropriate, because higher relapse rate after one week regimen indicates incomplete eradication leading to recrudescence. A 4 drug regimen (PPI + tetracycline + CBS + metronidazole) has also been advocated.

All regimens are complex and expensive, side effects are frequent and compliance is poor. Higher failure rates (20–40%) of H. pylori eradication have been reported from India. Also, 5 year recurrence rate of H. pylori infection is higher. Three week treatment is now being advocated. Nevertheless, long-term benefits of anti-H. pylori therapy include lowering of ulcer disease prevalence and prevention of gastric carcinoma/lymphoma; but benefits in nonulcer dyspepsia are equivocal.

H. pylori vaccines are under development.

Some available anti-H. pylori kits (one kit to be taken daily in 2 doses)

HPKIT, HELIBACT, OMXITIN: Omeprazole 20 mg 2 cap + Amoxicillin 750 mg 2 tab + Tinidazole 500 mg 2 tab.

PYLOMOX: Lansoprazole 15 mg 2 cap + Amoxicillin 750 mg 2 tab + Tinidazole 500 mg 2 tab.

LANSI KIT: Lansoprazole 30 mg 1 cap + Amoxicillin 750 mg 1 tab + Tinidazole 500 mg 1 tab (one kit twice a day)

PYLOKIT, HELIGO: Lansoprazole 30 mg 2 cap + Clarithromycin 250 mg 2 cap + Tinidazole 500 mg 2 tab. LANPRO AC: Lansoprazole 30 mg 2 cap + Clarithromycin 250 mg 2 tab + Amoxicillin 750 mg 2 tab.