Pantoprazole Clarithromycin

Adamek Szymanski C, Pfaffenbach B, et al (1995) Short term triple therapy with pantoprazole, clarithromycin and metronidazole for the healing of Helicobacter pylori infection. Dtsch Med Wochenschr 120 358-360... 

There is increasing evidence that eradication of Helicobacter pylori with combination therapy of two antibiotics (often amoxicillin with clarithromycin) with a proton pump inhibitor (e.g. pantoprazol) during one week will heal and prevent peptic ulcer disease. 

Amoxycillin 1 g twice daily plus clarithromycin 500 mg twice daily, plus esomeprazole 20 mg twice daily (or lansoprazole 30 mg twice daily or pantoprazole 40 mg twice daily or daily or ranitidine bismuth citrate 400 mg twice daily or rabeprazole 20 mg twice daily)... 

Lamouliatte H, Samoyeau R, De Mascarel A, Megraud F. Double vs. single dose of pantoprazole in combination with clarithromycin and amoxycillin for 7 days, in eradication of Helicobacter pylori in patients with non-ulcer dyspepsia. Aliment Pharmacol Ther 1999 13(ll) 1523-30. 

When 11 healthy suhjeets taking omeprazole 40 mg daily were also given elarithromyein 500 mg every 8 hours for 5 days, the maximum serum levels of omeprazole rose hy 30% and its AUC0.24 rose by 89%, but the effeet of omeprazole on gastrie pH was unchanged. The maximum serum clarithromycin levels rose by 11% and the AUC0.8 was increased by 15%. In a similar study, approximately twofold increases in the AUC of omeprazole were reported. In another study in 8 subjects (all extensive metabo-lisers of CYP2C19), clarithromycin 500 mg twice daily for 7 days caused a similar twofold increase in the AUC of omeprazole 20 mg twice daily but did not affect the AUC of pantoprazole 40 mg twice daily. The levels of clarithromycin itself were not affected. ... 

The pharmacokinetic interactions between clarithromycin and omeprazole, esomeprazole and lansoprazole are established. However, none of the changes reported represents an adverse interaction, but they may help to explain why concurrent use is valuable in the eradication of Helicobacter pylori. Erythromycin is likely to interact similarly, whereas roxithromycin does not. Pantoprazole is not affected by macrolides. 

Calabresi L, Pazzucconi F, Ferrara S, di Paolo A, Del Tacca M Sirtori C Pharmacokinetic interactions between omeprazole/pantoprazole and clarithromycin in healthy volunteers Pharmacol Res (2004) 49,493-9... 

Mayr-Kanhauser S, Knmke B, Kaddu S, MuUegger RR (2(X)1) Resolution of granulomatous rosacea after eradication of Helicobacter pylori with clarithromycin, metronidazole and pantoprazole. Em J Gastroenterol Hepatol 13 1379-1383... 

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. 

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. 

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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