Are there any reports of interactions between bismuth (De-Nol) and doxycycline or between these two

Fråga: Are there any reports of interactions between bismuth (De-Nol) and doxycycline or between these two drugs and the following drugs: epoetin beta, celecoxib, tramadol, lansoprazole and paracetamol?

The question concerns a 55-year-old patient with helicobacter pylori associated atrophic gastritis and myelodysplastic syndrome. During the past year he has been treated with different drug combinations to eliminate helicobacter pylori including omeprazole+amoxycillin+metronidazole and clarithromycine+metronidazole+lansoprazole. A third alternative Vismut (De-nol)+lansoprazole+doxycycline is under consideration. Other medications include NeoRecormon (epoetin beta), Celebra (celecoxib), Nobligan (tramadol), and Alvedon (paracetamol).

Sammanfattning: Bismuth is known to reduce the bioavailability of doxycycline by about 30-50 percent. Theoretically, lansoprazole can increase the absorption of bismuth due to increase in gastric pH. Also, lansoprazole raises gastric pH which would decrease the solubility and absorption of tetracyclines. It is however doubtful whether any of these interactions negatively affects the efficacy of tetracyclines in treating helicobacter pylori infections. It might still be prudent to give doxycycline on a separate occasion than bismuth and lansoprazole. We found no reports of interactions between doxycycline or bismuth and epoetin beta, celecoxib, tramadol or paracetamol.

Svar: Tetracyclines are known to interact with antacids including bismuth (1). In particular, bismuth has been shown to reduce the bioavailability of doxycycline by about 30-50 percent through interference with absorption (2). On the other hand the gastric absorption of bismuth may be increased by drugs such as omeprazole, which increase gastric pH.

In one study, Treiber et al (3) gave tripotassium dicitrato bismuthate 240 mgx1 to six healthy subjects with and without pre-treatment with omeprazole 40 mg per day for 7 days. The area under the plasma concentration time curve of bismuth in the patients who were pre-treated with omeprazole was 3 times larger than in those who were not pre-treated with omeprazole. Although the effect of lansoprazole on bismuth has not been studied, it would probably also increase the absorption of bismuth in a similar way. The clinical relevance of increased bismuth concentration is unknown, but cases of severe central nervous system adverse reactions have been reported after consumption of 10-20 g salts of bismuth daily for many months (4).

Treatment with lansoprazole and other proton pump inhibitors leads to increased gastric pH. An increase of pH above 4 would decrease the solubility of tetracyclines and consequently their absorption (1). The clinical significance of such an interaction is unclear. Interestingly, the clinical efficacy of the triple therapy of tetracycline, bismuth, which is known to decrease the systemic availability of tetracycline, and metronidazole is not affected (5).

In an extensive literature search we found no reports of interactions between doxycycline or bismuth and epoetin beta, celecoxib, tramadol or paracetamol. 1 Stockley IH. Drug interactions. 5th ed. London: The Pharmaceutical Press; 1999: 194 2 Drugline no 07039 (year 1988) 3 Treiber G, Walker S, Klotz U. Omeprazole-induced increase in the absorption of bismuth from tripotassium dicitrato bismuthate. Clin Pharmacol Ther 1994; 55: 486-91 4 Drugline no 12198 (year 1995) 5 Klotz U. Pharmacokinetic considerations in the eradication of Helecobacter Pylori. Clin Pharmacokinet 2000; 38: 243-270