Lansoprazole + amoxicillin clarithromycin

Dual therapy - In combination with clarithromycin (omeprazole) or amoxicillin (lansoprazole). 

In a similar study in 221 patients with peptic ulcer disease associated with H. pylori, rabeprazole has been compared with omeprazole and lansoprazole (combining them with amoxicillin plus clarithromycin for 1 week) (6). Rabeprazole was as effective as omeprazole and lansoprazole in eradicating H. pylori (84-88% each). There were no differences in reported adverse events. Common adverse effects were soft stools, glossitis, taste disturbances, and skin rashes. 

The presence of a defective CYP2C19 allele has been associated with improved Helicobacter pylori cure rates after dual (omeprazole and amoxicillin) or triple therapy (omeprazole, amoxicillin, and clarithromycin) with omeprazole, as weU as with lansoprazole. This difference likely reflects the higher achievable intragastric pH in the PM group. The cure rate achieved with dual therapy was 100% in PMs compared with 60% and 29% in heterozygous and homozygous EMs, respectively. In two studies, EMs had H. pylori... 

Mainz D, Bomer K, Koeppe P, Kotwas J, Lode H. Pharmacokinetics of lansoprazole, amoxicillin and clarithromycin after simultaneous and single administration JAntimicrob Chemoti-er(2002) 50.699-706. 

The treatment paradigm that is most frequently used is triple therapy with PPIs in combination with amoxicillin and clarithromycin. Usually this is a twice-daily treatment with omeprazole/lansoprazole/pantoprazole at standard dose with 1 g amoxicillin and 500 mg clarithromycin taken simultaneously, which in trials have given 90% eradication. Metronidazole may be used in substitution for either antibiotic. 

Dual therapy - 30 mg lansoprazole plus 1 g amoxicillin both taken 3 times/day for 14 days for patients intolerant or resistant to clarithromycin. 

Triple therapy- 30 mg lansoprazole plus 500 mg clarithromycin and 1 g amoxicillin all taken twice/day for 10 to 14 days. 

Clarithromycin/Lansoprazole/Amoxicillin- 500 mg clarithromycin, 30 mg lansoprazole, and 1 g amoxicillin every 12 hours for 10 or 14 days. 

The study population consisted of CYP2C19-genotyped patients infected with H. pylori who had completed initial treatment with omeprazole 20 mg or lansoprazole 30 mg twice daily, and clarithromycin 200 mg and amoxicillin 500 mg three times a day for 1 week. Patients in whom the infection was not eradicated after initial treatment were retreated with lansoprazole 30 mg and amoxicillin 500 mg four times a day for 2 weeks. 

Sucralfate 1 g tds in combination with amoxicillin 500 mg tds and clarithromycin 400 mg bd for 2 weeks was as effective as a combination of lansoprazole 30 mg bd plus amoxicillin 500 mg tds and clarithromycin 400 mg bd for 2 weeks for H. pylori eradication in a randomized, multicenter trial in 150 patients (9). There was no significant difference in adverse effects between the two groups. Diarrhea, abdominal pain, glossitis, and taste disturbance were the adverse effects commonly reported. 

Regarding proton pump inhibitors, the effect of CYP2C19 PM status is not limited to pharmacokinetic alterations. The difference in the pharmacokinetics has been shown to influence the outcome of H. Pylori eradication therapy. Furuta et al. showed that in patients with confirmed H. Pylori infection treated with omeprazole or lansoprazole plus clarithromycin and amoxicillin, CYP2C19 PMs had an eradication rate of 97.8% compared with a rate of 72.7% (P < 0.001) for CYP2C19 EMs (51). 

Proton pump inhibitor-based three-drug regimens Omeprazole 20 mg twice daily Clarithromycin 500 mg twice or lansoprazole 30 mg twice daily daily or pantoprazole 40 mg twice daily or esomeprazole 40 mg daily or rabeprazole 20 mg daily Bismuth-based four-drug regimens Amoxicillin 1 g twice daily or metronidazole 500 mg twice daily ... 

The AUC of a single 60-mg dose of lansoprazole was raised 1.55-fold to 1.8-fold by clarithromycin 500 mg twice daily for 6 days in both extensive and poor metabolisers of CYP2C19. In another study in healthy subjects, the AUC of lansoprazole 30 mg twice daily was increased by just 25% by clarithromycin 500 mg twice daily and amoxicillin 1 g twice daily for 4 days. The AUC of the hydroxyl metabolite of clarithromycin was also increased by about 25%. ... 

Esomeprazole, lansoprazole and omeprazole do not alter the pharmacokinetics of amoxicillin, and omeprazole does not alter bacampicillin bioavailability. Isolated reports describe glossitis, stomatitis and/or black tongue in a small number of patients when treated with lansoprazole and antibacterials, which included amoxicillin, clarithromycin and metronidazole. 

A study in 12 healthy subjects found no significant changes in the pharmacokinetics of amoxicillin 1 g twice daily when it was given with lansoprazole 30 mg twice daily and clarithromycin 500 mg twice daily for 4 days. Other randomised, crossover studies in a total of 36 healthy subjects also found no changes in the bioavailability or half-life of amoxicillin 1 g twice daily when it was given with clarithromycin 500 mg twice daily and either esomeprazole 20 mg twice daily or 40 mg once daily for 7 days. ... 

Thus, combinations of various PPIs, such as pantoprazole, lansoprazole, or omeprazole, used with clarithromycin and amoxicillin or metronidazole have all been reported to produce eradication rates and ulcer healing in excess of 90% and as high as 96%. An issue is the duration of therapy. It seems that 7 days of twice-daily combination therapy is required for effective eradication. Continued therapy with the PPI for 4 weeks is still suggested for ulcer healing, but some studies indicate that eradication is sufficient for ulcer healing, without the need for acid suppression. However, it is necessary to show a negative breath test within 1 week of therapy to enable this strategy. 

In trials so far performed with pantoprazole or lansoprazole, equivalent efficacy has been shown. It can be seen that any two of the three antibiotics in combination with omeprazole reach the eightieth percentile eradication. However, only those containing clarithromycin reach the ninetieth percentile. It is also clear that two antibiotics are ineffective, as is omeprazole alone. There is now more evidence that resistance to clarithromycin is increasing, and some instances of resistance to amoxicillin have been found. Metronidazole resistance is found rather frequently in those populations in which treatment with the nitroimidazoles for other diseases was prevalent. It must be admitted, however, that outside the clinical trial setting, eradication rates fall to approximately the seventieth percentile. Also, resistance to clarithromycin is also increasing. 

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