Ranitidine bismuth citrate

BSS, bismuth subsalicylate H2RA, H2-receptor antagonist PPI, proton pump inhibitor RBC, ranitidine bismuth citrate (not available in the United States). 

Clarithromycin/Ranitidine bismuth citrate-500 mg clarithromycin 2 times/day (every 12 hours) or 3 times/day (every 8 hours), and 400 mg ranitidine bismuth citrate given 2 times/day (every 12 hours) for 14 days. An additional 14 days of ranitidine bismuth citrate 2 times/day is recommended for ulcer healing and symptom relief. This combination is not recommended in patients with a creatinine clearance (Ccr) less than 25 mL/min. 

Acute porphyria Do not use clarithromycin in combination with ranitidine bismuth citrate in patients with a history of acute porphyria. 

Vondracek TG. Ranitidine bismuth citrate in the treatment of Helicobacter pylori infection and duodenal ulcer. Ann Pharmacother 1998 32(6) 672-9. 

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)... 

Finally, it is universally accepted at present that Helicobacter pylori infection has a definitive ethiological role in peptic ulcer disease, and that erradication therapy is warranted in these clinical scenarios. The majority of therapeutic trials have included the application of triple therapy with proton pump inhibitors or ranitidine bismuth citrate, clarithromycin and either amoxycillin or metronidazol and is to date the treatment of choice. However, recent studies have reported antibiotic resistance which can be one reason for failure of treatment of Helicobacter pylori infection [101-103], and new treatment strategies are therefore Wellcome. Flavonoids, in addition to their gastroprotective activity previously commented, have been also shown to inhibit Helicobacter pylori growth in vitro. In this way, Beil et al. [50]... 

CBS = colloidal bismuth subcitrate RBC = ranitidine bismuth citrate approximate formulas. 

Proton pump inhibitor or ranitidine bismuth citrate (as Ranitidine Bismutrex) b.d. + clarithromycin 500 mg b.d. + amoxycillin Ig b.d. for 7 days. 

Bismuth salts are still in use. Tripotassium dicitrato-bismuthate and bicitropeptide (a bismuth-peptide complex) are used in the eradication of Helicobacter pylori in combination with antibiotics (SEDA-21,233) (1 ), and ranitidine bismuth citrate is used to treat peptic ulcer (5). Bismuth salicylates are used in other intestinal diseases, such as microscopic colitis (6,7) and collagenous colitis (8). Bismuth subnitrate plus iodoform is used to pack surgical cavities. Bismuth oxide and bismuth subgallate are found in some topical formulations that are used for treating hemorrhoids. Bismuth is also used topically as a bacteriostatic. 

Data from 20 clinical studies in 5000 patients who had taken ranitidine bismuth citrate (200, 400, or 800 mg bd) have been reported (14). The incidence of adverse events was not different from that associated with placebo and was independent of dose. The most common events (>1% of patients) were upper respiratory tract infections, constipation, diarrhea, nausea, vomiting, dizziness, and headache, the last being the only event reported by over 2% of the patients. Adverse events considered by the chnical investigator to be adverse reactions occurred with a similar frequency amongst patients given ranitidine bismuth citrate (8%), ranitidine hydrochloride (6%), and placebo (6%). The incidence of adverse reactions was greater when amoxicillin (11%) or clarithromycin (20%) were co-prescribed. 

Van Oijen AH, Verbeek AL, Jansen JB, De Boer WA. Review article treatment of Helicobacter pylori infection with ranitidine bismuth citrate- or proton pump inhibitor-based triple therapies. Aliment Pharmacol Ther 2000 14(8) 991-9. 

Pipkin GA, Mills JG, Kler L, Dbcon JS, Wood JR. The safety of ranitidine bismuth citrate in controlled clinical studies. Pharmacoepidemiol Drug Saf 1996 5(6) 399 107. 

In patients with renal insufficiency the elimination of H2 receptor antagonists is subject to significant and clinically relevant alterations (18). Doses should be reduced, and ranitidine bismuth citrate should be avoided altogether in severe renal insufficiency. 

H. pylori when given with ranitidine bismuth citrate and metronidazole. Aliment. Pharmacol. Then 13, 651-659. 

Bismuth-containing preparations (e.g., those containing colloidal bismuth subcitrate) have effects similar to those of sucralfate, apparently because of their similar physical properties and coating effects. A combination of ranitidine-bismuth citrate is used with clarithromycin for eradication of H. pylori in the treatment and prevention of recurrence of duodenal ulcers. Combinations of bismuth subcitrate with other antibiotics and with H2 antihistamines also are used. Bismuth subsalicylate is used in this way as well. 

However, the manufacturers of TDB say that the toxic range of bismuth is arbitrary and a small increase in absorption is not clinically relevant, except perhaps in patients with renal failure, in whom this bismuth compound should be avoided in any case. Note that a complex of ranitidine with bismuth and citrate (ranitidine bismuth citrate) is available in many countries and is a recommended constituent in one of the triple therapy regimens for H. pylori eradication. As with all bismuth compounds, it is recommended that this is used only for limited periods a maximum of 16 weeks (two 8-week courses or four 4-week courses) in a 12-month period. ... 

Interestingly, all of the elements in group 15 in the periodic table (N, P, As, Sb and Bi) are directly or indirectly related to the maintenance of human life as either essential elements (e.g., N and P) or therapeutic/toxic elements (e.g.. As, Sb and Bi). Currently antimony compounds (e.g., sodium stibogluconate, Pentostam ) are used clinically for the treatment of leishmaniasis and bismuth compounds (e.g., bismuth subsalicylate (BSS), colloidal bismuth subcitrate (CBS) and ranitidine bismuth citrate (RBC)) are widely used for the treatment of ulcer and Helicobacter pylori infection [l-3c,10,132,133]. Recently, clinical... 

Scheme 5.7 The basic BP citrate dimer found in the antiulcer drugs, colloidal bismuth subcitrate (CBS, DE-Nol ) and possibly ranitidine bismuth citrate. Assembly of these building block leads to the formation of polymeric anion.

Figure 5.7 2D [ H, C] HSQC NMR spectrum of 5 mM ranitidine bismuth citrate showing different forms of bound citrate. Adapted with permission from J. A. Parkinson et al., Chem. Commun. 881 (1998) [138], Reproduced by permission of The Royal Society of Chemistry.

Eradication therapy is mainly carried out as a one-week triple therapy, i.e. a proton pump inhibitor (PPI) combined with amoxicillin and clarithromycin or metronidazole. Bismuth or Ranitidine bismuth citrate triple therapies are also prescribed, as... 

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