Antimuscarinics in Older People: Dry Mouth and Beyond.

Many common prescription and over-the-counter medications have antimuscarinic effects. Antimuscarinics are a well recognized cause of dry mouth, with potential to cause other physical and cognitive adverse effects. A comprehensive medication review in a patient presenting with dry mouth can lead to overall health improvements. Scoring systems can be helpful in identifying antimuscarinic drugs and their adverse effects. CPD/Clinical Relevance: Antimuscarinic drug use is prevalent and a common cause of dry mouth. Older people are particularly susceptible to antimuscarinic adverse effects.

A randomized trial comparing omeprazole, ranitidine, cisapride, or placebo in helicobacter pylori negative, primary care patients with dyspepsia: the CADET-HN Study.

BACKGROUND: The management of Helicobacter pylori negative patients with dyspepsia in primary care has not been studied in placebo-controlled studies. METHODS: H. pylori negative patients with dyspepsia symptoms of at least moderate severity (> or =4 on a seven-point Likert scale) were recruited from 35 centers. Patients were randomized to a 4-wk treatment of omeprazole 20 mg od, ranitidine 150 mg bid, cisapride 20 mg bid, or placebo, followed by on-demand therapy for an additional 5 months. Treatment success was defined as no or minimal symptoms (score < or = 2 out of 7), and was assessed after 4 wk and at 6 months. RESULTS: Five hundred and twelve patients were randomized and included in the intention-to-treat (ITT) analysis. At 4 wk, success rates (95% CI) were: omeprazole 51% (69/135; 43-60%), ranitidine 36% (50/139, 28-44%), cisapride 31% (32/105, 22-39%), and placebo 23% (31/133, 16-31%). Omeprazole was significantly better than all other treatments (p < 0.05). The proportion of patients who were responders at 4 wk and at 6 months was significantly greater for those receiving omeprazole 31% (42/135, 23-39%) compared with cisapride 13% (14/105, 7-20%), and placebo 14% (18/133, 8-20%) (p= 0.001), but not ranitidine 21% (29/139, 14-27%) (p= 0.053). The mean number of on-demand study tablets consumed and rescue antacid used was comparable across groups. Economic analysis showed a trade-off between superior efficacy and increased cost between omeprazole and ranitidine. CONCLUSION: Treatment with omeprazole provides superior symptom relief compared to ranitidine, cisapride, and placebo in the treatment of H. pylori negative primary care dyspepsia patients.

Evidence-based analysis: postoperative gastric bleeding: etiology and prevention.

Although the incidence of stomach hemorrhage is declining, stress-related gastric bleeding remains an important source of morbidity and mortality in cancer patients undergoing major surgical procedures to remove tumor. Prevention of stress-related bleeding is desirable; however, the optimal use of drugs to prevent gastric bleeding is unclear. Prophylaxis is recommended for surgical patients who require prolonged mechanical ventilation or have a coaguloathy. Histamine-2 receptor antagonists and sucralfate will reduce the likelihood of clinically important gastric-bleeding. Sucralfate appears to be less effective than H-2 blockers, but it is associated with fewer side effects such as nosocomial pneumonia. Preliminary studies show that proton pump inhibitors are most effective, have few side effects, but are most expensive. Intravenous proton pump inhibitors may be the drugs of choice for stress ulcer prophylaxis (SUP) in high-risk patients.

Helicobacter pylori-positive duodenal ulcer: three-day antibiotic eradication regimen.

BACKGROUND: The most widely used treatments for ulcer healing and Helicobacter pylori eradication consist of a 1-2 week regimen of a proton pump inhibitor plus two or three antimicrobials. AIMS: To evaluate the efficacy, safety, cost, and tolerance of a three-day regimen with three antibiotics vs. a 10-day treatment with a proton pump inhibitor or vs. a ranitidine bismuth citrate triple therapy. METHODS: Two hundred and twenty-one patients with endoscopically-proven H. pylori-positive duodenal ulcers were recruited to the study. Recruited patients were assigned to one of the following four regimens: (I) omeprazole 40 mg o.m. plus amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. for 10 days (OAC: 55 patients); (ii) omeprazole 40 mg o.m. on days 1-5, plus amoxycillin 1 g b.d., clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. on days 3-5 (OACM: 56 patients); (iii) ranitidine bismuth citrate 400 mg b.d. plus amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. for 10 days (RAC: 54 patients); (iv) ranitidine bismuth citrate 400 mg b.d. on days 1-5, plus amoxycillin 1 g b.d., clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. on days 3-5 (RACM: 56 patients). Fisher's exact test was used to compare data regarding healing and eradication in the four groups. RESULTS: The intention-to-treat eradication and ulcer healing rates for the RACM regimen were 95% and 98%, respectively. Statistically significant differences were observed, relating to the eradication and healing of ulcers, between RACM and either the RAC or OAC regimens. CONCLUSION: The three-day antibiotic therapy with amoxycillin, clarithromycin and metronidazole in addition to ranitidine bismuth citrate is a very effective anti-H. pylori regimen.

The use of intravenous H2-receptor antagonists in a tertiary care hospital.

OBJECTIVE: The rationale for the widespread use of intravenous H2 receptor antagonists(IVH2 RA) in hospitalized patients is not clear. We therefore examined prescribing patterns and, using strict criteria, determined whether use was appropriate. Cost of administration and potential savings were also determined. METHODS: Data were obtained prospectively on 100 consecutive patients prescribed intravenous ranitidine and retrospectively on patients admitted with gastrointestinal (GI) bleeding. RESULTS: For the prospective study, various indications for prescribing intravenous ranitidine were given, including postoperative patients and patients treated with steroids. Using criteria from published literature 80% of the use was considered inappropriate. Nearly 40% of the doses were given while the patient was tolerating oral intake. Creatinine clearance was impaired in 26% of patients, though only one had dosage reduction. Estimated annual cost of intravenous ranitidine was $317,000. The retrospective study of 86 consecutive patients admitted with GI bleeding revealed that all patients received intravenous ranitidine on admission, none of which was considered appropriate. The final diagnoses were peptic ulcer (49), colonic process (11), esophagitis (seven), gastric erosions (five), esophageal varices (five), Mallory-Weiss tears (four), duodenitis (two), no diagnosis (three), and jejunal ulcer (one). CONCLUSIONS: Inappropriate use of intravenous ranitidine is common. This includes inappropriate indication, dosage, and duration of use. Large financial benefits could have been obtained if close attention was given to prescribing patterns.

H2-antagonist maintenance therapy versus Helicobacter pylori eradication in patients with chronic duodenal ulcer disease: a prospective study.

BACKGROUND: Few outcome studies directly compare Helicobacter pylori eradication therapy with maintenance H2-antagonist therapy in duodenal ulcer disease. AIM: To examine prospectively the efficacy of H. pylori eradication therapy with ranitidine maintenance therapy over 1 year in patients with confirmed chronic duodenal ulcer. METHODS: One hundred and nineteen patients with active H. pylori infection were randomized to receive ranitidine, 150 mg/day initially (58 patients), or omeprazole, 40 mg/day, amoxycillin 2 g/day and metronidazole 1.2 g/day for 14 days, or omeprazole 40 mg/day and clarithromycin 1.5 g/day, for 14 days (if penicillin-allergic). Symptoms were assessed using the Gastrointestinal System Rating Scale (GSRS) and SF36 quality of life index. RESULTS: 13C urea breath testing confirmed overall treatment success in 100% of patients (58/58) per protocol and 95.1% (58/61) on an intention-to-treat basis. At 4 and 12 months there were no differences in any GSRS symptoms between treatment groups. SF36 analysis showed a perceived health improvement at 4 and 12 months in patients who received H. pylori eradication. However, despite successful H. pylori eradication, one-fifth of patients still required antisecretory therapy. CONCLUSION: Following successful H. pylori eradication, chronic duodenal ulcer patients were at least as well symptomatically as when taking maintenance ranitidine. They perceived that their health had improved, but a subgroup was still acid-suppression dependent.

Triple therapy with ranitidine or lansoprazole in the treatment of Helicobacter pylori-associated duodenal ulcer.

OBJECTIVE: The aim of this study was to verify the efficacy--in the cure of duodenal ulcer associated H. pylori infection--of ranitidine 300 mg taken late in the evening or lansoprazole 30 mg taken before breakfast, coupled with clarithromycin and metronidazole. METHODS: Eighty patients with endoscopically proven active duodenal ulcer were randomized to take ranitidine or lansoprazole for 4-8 wk, together with clarithromycin 250 mg b.i.d. and metronidazole 500 mg b.id. for the first 2 wk. Endoscopic controls, as well as histological and urease tests for H. pylori, were performed at entry and after 4 and 8 wk. RESULTS: According to intent-to-treat analysis, ulcers were healed after 4 wk in 36/40 patients (90%) with ranitidine and in 38/40 (95%) with lansoprazole. After 8 wk, the healing percentage with ranitidine and lansoprazole was 97% (39/40) and 95% (38/40), respectively. H. pylori was eradicated in 85% of the patients taking ranitidine and in 90% of those taking lanzoprazole. Side effects were reported in 25% of the patients in both groups. CONCLUSIONS: Our results confirm that the combination of ranitidine, clarithromycin, and metronidazole can be considered an alternative to proton pump inhibitors in terms of clinical efficacy and economy.

Quality problems that result in adverse outcomes provide opportunities for quality improvement.

Patient suffers central nervous system damage after prolonged use of metoclopramide and ranitidine hydrochloride to control gastroesophageal reflux. Treatment is complicated by poor communication among providers and omissions in history-taking.

How Zantac became the best-selling drug in history.

Glaxo's Zantac began its dominance of the acid/peptic marketplace with a launch strategy, taking advantage of the established Roche sales force to rapidly promote the product. Educational symposia for physicians were instrumental in disseminating both disease and product information to primary care physicians and specialists. This technique not only pleased physicians (more referrals), but also increased public awareness of gastrointestinal disease, further expanding the patient market. Several novel marketing strategies contributed to Zantac's success, including the public-service announcements, celebrity media tours, and consumer-awareness bulletins, which brought the drug to the lay public and encouraged individuals to seek advice from their physicians.

Ranitidine-associated autoimmune hemolytic anemia in a health maintenance organization population.

Reversible hematologic abnormalities including hemolytic anemia [1] with a positive direct Coombs' test have been associated with ranitidine. In addition to the case report cited above, the U.S. Food and Drug Administration had received five other cases of hemolysis associated with recent intake of ranitidine as of February 1991. To investigate the possible association of ranitidine with autoimmune hemolytic anemia, a study was conducted to determine how often diagnoses of hemolytic anemia or abnormal Coombs' test results followed dispensing of ranitidine using the automated medical and pharmacy records of a large health maintenance organization. No occurrences of hemolytic anemia were identified among 12,054 individuals following 38,686 prescriptions for this medication. The 95% upper confidence bound was 3.1 cases/10,000 exposed persons. One abnormal direct Coombs' test with mild anemia was discovered during routine prenatal testing of an asymptomatic patient who was dispensed ranitidine two and a half months previously. Hemolysis, however, was not demonstrated and an association with prior ranitidine use could not be confirmed. Additional analyses indicate that in only 30% of ranitidine courses was a blood count obtained. In those courses with hematocrits below 40%, less than 1% had a Coombs' test performed. Chart review suggests that the majority of individuals with severe anemia have alternative explanations other than autoimmune hemolysis for their anemia. This analysis indicates that ranitidine is unlikely to be a common cause of clinically recognized autoimmune hemolytic anemia and demonstrates the utility of large automated medical and pharmacy data bases to conduct post-marketing studies of spontaneously reported drug effects.

Inaccurate assessment of drug-induced thrombocytopenia: reason for concern.

OBJECTIVE: To report two cases in which patients were reputed to have exhibited thrombocytopenia secondary to the histamine-receptor blocking agent ranitidine. Evaluation and the associated time frame of events failed to confirm these observations. DESIGN: Two case studies. RESULTS: Ranitidine was ordered as part of the therapeutic course of two patients admitted to the medicine service. The development of thrombocytopenia in both patients was attributed to this agent and it was discontinued. In addition to ranitidine, both patients received several other agents with greater potential to cause thrombocytopenia, and had a time course of development of the adverse effect that would not support ranitidine as the offending agent. Both patients required histamine-receptor antagonists at some point following their discontinuation and, based on the available evidence, the pharmacy suggested that these agents be restarted. In neither case did restarting the histamine-receptor antagonist lead to recurrence of thrombocytopenia. CONCLUSIONS: Although ranitidine can cause thrombocytopenia, the reported incidence is very low. Spontaneous reporting of adverse effects is essential in establishing a true pattern of safety for a drug. However, reports need to be scrutinized before they are rolled into the collective intelligence. Overzealous or incomplete reporting will lead to cautions that are either unnecessary or, because they deny people necessary treatment, dangerous.

Clinical appropriateness, therapeutic equivalence, and cost of conversion of H2 antagonist therapy.

A 12-month drug monitoring program targeting the use of H2 antagonists was initiated at the Erie County Medical Center, a 650-bed academic teaching hospital in Buffalo, NY. Discussed in this article are the development of indicators used to determine appropriateness of therapy, implementation of a H2 antagonist monitoring and screening program, examination of the effect of the program on budgetary expenditures for H2 antagonist therapy, evaluation of adverse effects and potential drug interactions associated with drug use, and measurement of possible drug cost savings resulting from the implementation of the program.

Clinical significance of hypergastrinaemia: relevance to gastrin monitoring during omeprazole therapy.

During the early experience with omeprazole, it was recommended that plasma gastrin levels be monitored to identify patients with 4-5-fold increases above baseline. Such patients were thought to be at an increased risk of developing gastric carcinoid tumours. Studies have established that plasma gastrin levels usually rise 2-4-fold during omeprazole therapy, there being considerable inter- and intra-individual variation. Approximately 3.3% of patients have plasma gastrin levels above 400 pg/ml when treated continuously for 1 year. In clinical practice, it is not cost-effective to screen all patients to detect such a small percentage, particularly given the paucity of realistic treatment options in such patients, and the growing evidence that hypergastrinaemia during omeprazole treatment is of little, if any, clinical significance.

Retrospective analysis of formulary restriction demonstrates significant cost savings.

Concurrent and retrospective analyses of drug use may be needed to ensure that formulary conversions are achieving the desired results. The department of pharmaceutical services at Botsford General Hospital, a 325-bed community teaching hospital in Farmington Hills, Mich., analyzed the impact of a formulary H2-receptor antagonist conversion and demonstrated that quality of care was maintained with significant cost savings achieved.

Time-motion study of intravenous ranitidine admixtures.

This study determined the total preparation time, cost, and contamination rate associated with preparing 50-mL admixtures of ranitidine 50 mg from each of the following commercial source vials: 50 mg/2 mL unit-dose vial (treatment A), 50 mg/2 mL 10 mL multidose vial (treatment B), and 50 mg/2 mL 40 mL multidose vial (treatment C). The study consisted of two separate phases: phase I extemporaneous compounding and phase II batch manufacturing. Twelve technicians prepared ten admixtures from each source vial during each phase. All admixtures were tested for sterility; bacterial contamination was not observed. Multidose vials saved approximately $197 per 200 admixtures. Drug and personnel costs were reduced when batch manufacturing with 40-mL multidose vials was compared with extemporaneous compounding with unit-dose vials. Our study showed that multidose vials decreased the total preparation time and cost for making ranitidine admixtures during both extemporaneous compounding and batch manufacturing by reducing setup time, preparation time, and drug procurement cost.

Ranitidine and sucralfate as maintenance therapy for gastric ulcer disease: endoscopic control and assessment of scarring.

The efficacy of ranitidine (150 mg nocte), and sucralfate (1 g tds) as maintenance therapy to prevent gastric ulcer relapse was evaluated in a 12 month trial in 363 patients. The relapse rates were 8.8% at three months, 14.7% at six months, 18.1% at nine months, and 21.0% at 12 months for the ranitidine group and 14.7%, 21.3%, 29.9%, and 30.2% respectively for the sucralfate group. At nine and 12 months the cumulative relapse rates for the ranitidine group were significantly lower than those for the sucralfate group (p less than 0.05). In both groups ulcers recurred mainly from red scars observed at the endoscopic scarring stage. This indicated the necessity of drug treatment up to the white scar stage. The results suggest that ranitidine is effective in preventing gastric ulcer relapse.