The most common cause of peptic ulcer disease is a bacterium designated Helicobacter pylori that was first observed in gastric biopsy specimens in 1979 and has since been identified in every human population tested on six continents. The spiral- shaped, gram-negative bacterium causes acute and chronic gastritis, gastric ulcers, duodenal ulcers, gastric cancer, and a type of lymphoma; it is the most common single cause of infectious disease in the world. (See Helicobacter pylori and Ulcers a comprehensive review of H. pylori.) Last month the FDA approved two new combination drug products for the treatment of peptic ulcers: Glaxo Wellcome’s ranitidine bismuth citrate (Tritec) and Proctor & Gamble’s (P&G) bismuth subsalicylate plus tetracycline and metronidazole (Helidac).
Tritec (ranitidine bismuth citrate) for ulcers
Ranitidine bismuth citrate (RBC, Tritec / Glaxo) was approved for use in combination with clarithromycin (Biaxin / Abbott) for the treatment of active duodenal ulcer disease associated with H. pylori infection. RBC has cytoprotective effects and has also shown bactericidal activity, although the FDA-required labeling does not include statements concerning any antimicrobial effects. The product is available in 400-mg tablets equivalent to 162 mg ranitidine (Zantac / Glaxo), 128 mg trivalent bismuth, and 100 mg citrate. In clinical studies of RBC, 400 or 800 mg twice daily, in combination with clarithromycin, H. pylori eradication rates were from 73 to 84%. In trials comparing RBC with ranitidine alone, more patients were healed with RBC (86%) than with ranitidine alone (76%), and fewer patients relapsed during six-month follow-up.
Patients who are not cleared of H. pylori following therapy with RBC plus clarithromycin are considered to be clarithromycin-resistant; susceptibility testing should be performed, and if resistance is shown to clarithromycin (or if testing is not possible), an alternate therapy should be used. Additional trials are under way to determine if RBC/clarithromycin is superior to ranitidine alone plus clarithromycin, and to see if RBC reduces emerging resistance to clarithromycin.
Helidac (bismuth/TCN/metronidazole) for ulcers
P&G’s Helidac is a new product approved for H. pylori-associated duodenal ulcer disease; it is used in combination with a histamine2 antagonist. The product is a blister pack kit containing bismuth subsalicylate (Pepto-Bismol) plus generic tetracycline and metronidazole (by Ivax). There are 14 blister cards in each kit, and each card carries one day’s dosage (eight chewable tablets of bismuth subsalicylate 262.4 mg, four metronidazole 250-mg tablets, and four tetracycline 500-mg capsules). Tetracycline and metronidazole have proved to be effective as sole agents against most susceptible strains of H. pylori, but similar claims for bismuth subsalicylate await the completion of clinical trials. If Helicobacter pylori is not eradicated, the patient can be assumed to have a metronidazole- resistant strain.
Side effects are primarily gastrointestinal (nausea, diarrhea, abdominal pain, and melena). Helidac is contraindicated in patients with renal or hepatic impairment, in pregnant or nursing women (the tetracycline component can cause permanent tooth discoloration when administered during the last half of pregnancy and during infancy), and in children (the salicylate component increases risk of Reye’s syndrome and neurotoxicity, and the tetracycline can discolor teeth up to age eight). Labeling also cautions patients to avoid sun or sunlamp exposure and alcohol. Physical or pharmacologic interactions may occur with milk or dairy products, iron, zinc, antacids, anticoagulants, antidiabetic medication, probenecid, aspirin, sulfinpyrazone, sodium bicarbonate, penicillin, cimetidine, phenytoin, phenobarbital, lithium, and certain x-ray diagnostic procedures.
Originally posted 2010-03-17 08:41:21. Republished by Blog Post Promoter