Famotidine is used orally for the treatment of active duodenal or gastric ulcer, gastroesophageal reflux disease, endoscopically diagnosed erosive esophagitis, and as maintenance therapy for duodenal ulcer. Oral famotidine also is used for the management of pathological GI hypersecretory conditions. IV famotidine is used in hospitalized individuals with pathological GI hypersecretory conditions or intractable ulcers, or when oral therapy is not feasible.
Famotidine is used for the short-term treatment of endoscopically or radiographically confirmed active duodenal ulcer. Antacids may be used concomitantly as needed for relief of pain. In controlled studies in patients with endoscopically confirmed duodenal ulcers, reported rates of ulcer healing for famotidine were substantially higher than those for placebo. In a multicenter, double-blind study in patients with endoscopically confirmed duodenal ulcer, reported rates of ulcer healing for oral famotidine dosages of 40 mg at bedtime daily, 20 mg twice daily, or 40 mg twice daily vs placebo were 32, 38, or 34%, respectively, vs 17%, at 2 weeks; 70, 67, or 75%, respectively, vs 31%, at 4 weeks; and 82-83% for these famotidine dosage regimens vs 45% for placebo, at 8 weeks. Famotidine also produced greater reductions in daytime and nocturnal pain and antacid consumption than did placebo, with complete relief of pain in most patients usually occurring within 2 weeks after initiation of famotidine therapy.
Famotidine appears to be at least as effective as cimetidine or ranitidine for the short-term treatment of active duodenal ulcer. An oral famotidine dosage of 40 mg at bedtime daily generally appears to be more effective than an oral cimetidine dosage of 800 mg daily and as effective as an oral ranitidine dosage of 300 mg daily (as a single or divided dose) in this condition. In a multicenter, double-blind study in patients with endoscopically confirmed duodenal ulcers, 68-81 or 76% of ulcers were healed following administration of famotidine (20 mg twice daily, 40 mg at bedtime daily, or 40 mg twice daily) or ranitidine (150 mg twice daily), respectively, for 4 weeks and 87-92 or 90%, respectively, were healed following therapy for 8 weeks. In geriatric patients, famotidine and ranitidine, in dosages of 40 mg at bedtime daily and 150 mg twice daily, respectively, were equally effective in healing active duodenal ulcers and providing symptomatic relief; 57 and 51% of ulcers were healed following administration of famotidine and ranitidine, respectively, for 8 weeks. In several studies, there appeared to be little difference between famotidine and ranitidine in reductions of daytime and nocturnal pain and antacid consumption.
Daily bedtime doses of famotidine generally appear to be as effective as a twice-daily regimen of the drug in healing active duodenal ulcer, although the bedtime regimen may be slightly less effective than twice-daily regimens at 4 but not 8 weeks. Ulcer healing rates averaged 32, 34, or 38% at 2 weeks; 68-70, 75-81, or 67-77% at 4 weeks; and 83-87, 82-92, or 82-92 at 8 weeks following oral famotidine dosages of 40 mg at bedtime daily, 40 mg twice daily, or 20 mg twice daily, respectively. Antacid consumption appeared to be similar with the various famotidine dosage regimens employed. Evidence from a multicenter, controlled study indicates that healing rates for duodenal ulcers in patients receiving famotidine may not be affected substantially by cigarette smoking or alcohol consumption, although healing rates were slightly higher in nonsmokers than in smokers.
Safety and efficacy of long-term famotidine therapy for active duodenal ulcer have not been determined. Studies to date have been limited to short-term treatment of active duodenal ulcer, and the safety and efficacy of treatment for active disease beyond 8 weeks have not been determined. Most patients with duodenal ulcer respond to famotidine therapy during the initial 4-week course of therapy; an additional 4 weeks of therapy may contribute to healing in some patients. However, short-term famotidine therapy (i.e., up to 8 weeks) for the treatment of active duodenal disease will not prevent recurrence following acute healing and discontinuance of the drug. Current epidemiologic and clinical evidence supports a strong association between gastric infection with Helicobacter pylori and the pathogenesis of duodenal and gastric ulcers; long-term H. pylori infection also has been implicated as a risk factor for gastric cancer. For additional information on the association of this infection with these and other GI conditions, .
Conventional antiulcer therapy with H2-receptor antagonists, proton-pump inhibitors, sucralfate, and/or antacids heals ulcers but generally is ineffective in eradicating H. pylori, and such therapy is associated with a high rate of ulcer recurrence (e.g., 60-100% per year). Duodenal ulcers have recurred within 6 months in 52-73% of patients following discontinuance of famotidine therapy. The American College of Gastroenterology (ACG), the National Institutes of Health (NIH), and most clinicians currently recommend thatall patients with initial or recurrent duodenal or gastric ulcer and documented H. pylori infection receive anti-infective therapy for treatment of the infection. Although 3-drug regimens consisting of a bismuth salt (e.g., bismuth subsalicylate) and 2 anti-infective agents (e.g., tetracycline or amoxicillin plus metronidazole) administered for 10-14 days have been effective in eradicating the infection, resolving associated gastritis, healing peptic ulcer, and preventing ulcer recurrence in many patients with H. pylori-associated peptic ulcer disease, current evidence principally from studies in Europe suggests that 1 week of such therapy provides comparable H. pylori eradication rates. Other regimens that combine one or more anti-infective agents (e.g., clarithromycin, amoxicillin) with a bismuth salt and/or an antisecretory agent (e.g., omeprazole, lansoprazole, H2-receptor antagonist) also have been used successfully for H. pylori eradication, and the choice of a particular regimen should be based on the rapidly evolving data on optimal therapy, including consideration of the patient's prior exposure to anti-infective agents, the local prevalence of resistance, patient compliance, and costs of therapy.
Current evidence suggests that inclusion of a proton-pump inhibitor (e.g., omeprazole, lansoprazole) in anti-H. pylori regimens containing 2 anti-infectives enhances effectiveness, and limited data suggest that such regimens retain good efficacy despite imidazole (e.g., metronidazole) resistance. Therefore, the ACG and many clinicians currently recommend 1 week of therapy with a proton-pump inhibitor and 2 anti-infective agents (usually clarithromycin and amoxicillin or metronidazole), or a 3-drug, bismuth-based regimen (e.g., bismuth-metronidazole-tetracycline) concomitantly with a proton-pump inhibitor, for treatment of H. pylori infection. For a more complete discussion of H. pylori infection, including details about the efficacy of various regimens and rationale for drug selection, .
Famotidine is used in reduced dosage as maintenance therapy following healing of active duodenal ulcer to reduce ulcer recurrence. In placebo-controlled studies, duodenal ulcer recurrence rates after 3, 6, and 12 months ranged from 9-14, 16-30, and 23-38%, respectively, for 20 or 40 mg of famotidine at bedtime daily vs 39, 52-73, and 57-77%, respectively, for placebo. Because the efficacy of H2-receptor antagonists in preventing duodenal ulcer recurrence appears to be substantially reduced in patients who are cigarette smokers compared with nonsmokers, patients who are cigarette smokers should be advised of the importance of discontinuing smoking in the prevention of ulcer recurrence. Maintenance therapy with famotidine has not been studied for longer than 1 year in placebo-controlled studies, and the effect of maintenance therapy with the drug in patients with previously healed duodenal ulcers remains to be more fully evaluated.
Pathologic GI Hypersecretory Conditions
Famotidine is used for the treatment of pathologic GI hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine adenomas). Famotidine reduces gastric acid secretion and associated symptoms (including diarrhea, nausea, and epigastric burning and pain) in patients with these conditions. Antimuscarinics (e.g., isopropamide iodide) have been used concomitantly with famotidine to augment famotidine-induced inhibition of gastric acid secretion in some patients with GI hypersecretory conditions.
In a limited number of patients with GI hypersecretory conditions, famotidine has effectively inhibited gastric acid hypersecretion and produced inhibition of longer duration than cimetidine and somewhat longer than that of ranitidine. However, these drugs appear to be comparably effective for the treatment of hypersecretion when adequate, equipotent dosages are used and patient compliance is optimal. In one study, patients with GI hypersecretory conditions who were successfully treated with 1.2-9 or 0.6-5.4 g of cimetidine or ranitidine, respectively, alone daily subsequently were treated successfully with 50-800 mg of famotidine alone daily. Although famotidine, cimetidine, and ranitidine were equally effective in controlling gastric hypersecretion, substantially lower doses of famotidine were required and with less frequency than with cimetidine or ranitidine. Famotidine therapy alone or in combination with an antimuscarinic agent has been continued in a few patients for up to 34 months.
Famotidine is used for short-term treatment of active, benign gastric ulcer. The efficacy of famotidine in the treatment of gastric ulcer appears to be similar to that of cimetidine or ranitidine, with 40-47, 36-71, or 40-76% of ulcers healed at 4 weeks; 65-68, 66-95, or 68-90% healed at 6 weeks; and 64-80, 67-86, or 79-91% healed at 8 weeks following therapy with famotidine, cimetidine, or ranitidine, respectively. In several other studies in patients with gastric ulcer, famotidine promoted healing of ulcers in about 42-65, 60-95, and 78 to greater than 91% of patients after 4, 6, and 8 weeks of treatment, respectively. Response of gastric ulcers to famotidine therapy does not appear to be affected by patient age or gender, cigarette smoking, alcohol consumption, or duration of disease. Patients with a history of chronic gastric ulcers (history of disease of 10 years or longer) appear to respond as well to famotidine therapy as patients with a brief history of disease. Famotidine also generally produced greater reductions in pain (fasting, postprandial, nocturnal) and other symptoms (including belching, nausea, anorexia) and in antacid consumption than did placebo. Safety and efficacy of famotidine in the treatment of gastric ulcer have not been established for periods exceeding 8 weeks; therefore, use of the drug for more prolonged treatment of active disease or for maintenance therapy of previously healed gastric ulcer remains to be more fully evaluated. If famotidine is used in the treatment of gastric ulcer, it should be kept in mind that symptomatic response does not preclude the presence of gastric malignancy.
Current epidemiologic and clinical evidence supports a strong association between gastric infection with H. pylori and the pathogenesis of gastric ulcers, and the ACG, NIH, and most clinicians currently recommend that all patients with initial or recurrent gastric ulcer and documented H. pylori infection receive anti-infective therapy for treatment of the infection. The choice of a particular regimen should be based on the rapidly evolving data on optimal therapy, including consideration of the patient's prior exposure to anti-infective agents, the local prevalence of resistance, patient compliance, and costs of therapy
(See Duodenal Ulcer: Acute Therapy, in Uses.)For a more complete discussion of H. pylori infection, including details about the efficacy of various regimens and rationale for drug selection,.
Gastroesophageal Reflux Disease
Famotidine is used to provide short-term symptomatic relief of gastroesophageal reflux disease (GERD). Famotidine also is used for short-term treatment of esophagitis associated with gastroesophageal reflux, including endoscopically proven erosive or ulcerative disease. By increasing gastric pH, H2-receptor antagonists have relieved heartburn and other symptoms of reflux and have been associated with somewhat higher healing rates of endoscopically proven esophagitis when compared with placebo and have reduced antacid consumption.
Suppression of gastric acid secretion is considered by the ACG to be the mainstay of treatment for GERD, and a proton-pump inhibitor or histamine H2- receptor antagonist is used to achieve acid suppression, control symptoms, and prevent complications of the disease. The ACG states that a histamine H2- receptor antagonist administered daily in divided doses is effective in many patients with less severe GERD, and over-the-counter (OTC) antacids and histamine H2- receptor antagonists are appropriate for self-medication as initial therapy in such individuals. A histamine H2-receptor antagonist is particularly useful when taken before certain activities (e.g., heavy meal, exercise) that may result in acid reflux symptoms in some patients. The ACG states that H2-receptor antagonists generally may be used interchangeably, although the drugs may differ in potency and in their onset and duration of action. However, proton-pump inhibitors are more effective (i.e., provide more frequent and more rapid symptomatic relief and healing of esophagitis) than histamine H2-receptor antagonists in the treatment of GERD. Although higher doses and more frequent administration of histamine H2-receptor antagonists appear to increase their efficacy, such dosages are less effective and more expensive than proton-pump inhibitor therapy. Once-daily administration of a histamine H2-receptor antagonist at full dosage is not considered to be appropriate therapy for GERD.
Based on data from a limited number of patients, famotidine 20 mg administered twice daily appears to be at least as effective as famotidine 40 mg administered at bedtime and more effective than placebo in improving symptoms of gastroesophageal reflux in patients who had no evidence of endoscopically proven erosive or ulcerative disease. Within 2 weeks of therapy, symptomatic relief was reported in a higher percentage of patients receiving famotidine compared with those receiving placebo; symptoms improved in 82, 69, and 62% of these patients at 6 weeks for famotidine 20 mg twice daily, famotidine 40 mg at bedtime, or placebo, respectively. In controlled studies in patients with endoscopically evaluated gastroesophageal reflux disease, reported rates of ulcer healing for famotidine were higher than those for placebo. Healing rates from controlled studies employing various dosage regimens were approximately 48, 32-34, 29, and 7-18% at 6 weeks and 69, 50-54, 43, and 26-29% at 12 weeks for famotidine 40 mg twice daily, 20 mg twice daily, 40 mg at bedtime, and placebo, respectively. Patients receiving famotidine reported faster relief of daytime and nocturnal heartburn and greater reduction in antacid consumption than those receiving placebo. Nocturnal heartburn relief was reported in a higher percentage of patients receiving famotidine than those receiving placebo; nocturnal heartburn relief occurred in about 58, 50, and 49% of patients receiving famotidine 20 mg twice daily, 40 mg at bedtime, and placebo, respectively, while daytime heartburn relief occurred in approximately 56, 42, and 46% of such patients, respectively. In a study in patients with gastroesophageal reflux who had endoscopically evaluated erosive or ulcerative disease, reported rates of ulcer or erosion healing at 6 weeks were 48 and 42% in patients receiving famotidine 40 mg twice daily or ranitidine 150 mg twice daily, respectively, while at 12 weeks rates of healing were 71 or 60% in patients receiving famotidine 40 mg twice daily or ranitidine 150 mg twice daily, respectively. However, ranitidine was as effective as famotidine in improving symptoms of gastroesophageal reflux.
H2-receptor antagonists also have been used in combination with metoclopramide in a limited number of patients who failed to respond to an H2-receptor antagonist alone, but the ACG states that frequent and potentially severe adverse CNS effects of metoclopramide have appropriately decreased regular use of the drug for GERD. Although some clinicians have suggested that a histamine H2- receptor antagonist also may be used in combination with bethanechol in patients who fail to respond to a histamine H2-receptor antagonist alone, the ACG states that bethanechol has limited efficacy in the treatment of GERD.
Short-term therapy (i.e., up to 12 weeks) with H2-receptor antagonists for the treatment of GERD will not prevent recurrence following ulcer healing and discontinuance of such therapy. Esophagitis has recurred within 6 months in up to 80% of patients following discontinuance of H2-receptor antagonist therapy. Because GERD is considered a chronic disease, many patients with GERD require long-term, even lifelong, treatment. The ACG states that proton-pump inhibitors are effective and appropriate as maintenance therapy in many patients with the disease. Maintenance therapy with an H2-receptor antagonist also has been used to reduce recurrence of GERD. However, many patients initially responding to proton-pump inhibitors experience symptomatic relapse and failure of esophageal healing with subsequent use of a histamine H2-receptor antagonist.
For further information on the treatment of GERD, see Uses: Gastroesophageal Reflux, in Omeprazole 56:28.36.
Famotidine may be used for self-medication for relief of symptoms of occasional heartburn (pyrosis), acid indigestion (hyperchlorhydria), or sour stomach and for prevention of such symptoms caused by consumption of food or beverages. Famotidine also may be used in fixed combination with calcium carbonate and magnesium hydroxide (Pepcid Complete) for self-medication for relief of symptoms of occasional heartburn (pyrosis) associated with acid indigestion (hyperchlorhydria) or sour stomach.
Famotidine also has been used in a limited number of patients to control intragastric pH and/or stress-induced GI bleeding in critically ill patients (e.g., traumatized or postoperative patients, patients in shock or with respiratory insufficiency). In patients with GI bleeding secondary to duodenal or stress ulcers or gastritis, the drug may control GI bleeding and reduce the need for emergency surgery, but may not prevent bleeding recurrence. Additional study to further evaluate the effect of famotidine on morbidity and mortality in patients with these conditions is necessary.