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Objective: To evaluate the impact of including community pharmacists in strategies to alter excessive prescribing of antiulcer medications (AUMs) in a statewide drug utilization review (DUR) program. Mailing educational materials to physicians is a common intervention strategy of retrospective DUR programs. However, pharmacists are typically left out of this process, ignoring a possibly influential healthcare provider., Methodology: Patients without gastroesophageal reflux disease who received > or = 1.0 normalized therapeutic equivalents (e.g., 1.0 NTE = ranitidine 300 mg/d or omeprazole 20 mg/d) for five of six prior months were included. The pharmacists and physicians of these patients were divided into one of three geographically distinct groups: group 1 physicians received mailed materials only (pharmacists were not contacted); group 2 physicians and pharmacists received mailed materials only; and group 3 physicians and pharmacists received mailed materials, and the pharmacists were contacted by phone. Mean NTE and AUM costs were analyzed six months before and six months following the intervention., Results: One hundred thirty-eight, 329, and 248 patients were included in G1, G2, and G3, respectively. There was a 12.4%, 8.0%, and 14.0% reduction in NTE for G1, G2, and G3, respectively. G1 AUM cost decreased 7.7% ($7710); G2 decreased 6.8% ($14 037); G3 decreased 20.5% ($26722). The total decrease in AUM cost for the entire cohort from before to after the intervention was $48469 (p < 0.05) in the six months following the intervention., Conclusions: A follow-up phone call to pharmacists in a statewide DUR intervention enhances the effectiveness of DUR interventions under the conditions studied. Enlisting the support of community pharmacists may improve the cost savings of these interventions.

Objective: To document a case of anion gap, nonketotic metabolic acidosis occurring in a patient with acute renal failure who was receiving metformin., Case Summary: A 67-year-old white man presented with a 9-day history of weakness, nausea, dizziness, and difficulty moving; he had also not eaten during the previous 2 days. The patient had numerous abnormalities on his serum chemistry panel and arterial blood gases, including a pH of 7.1 and an anion gap of 21 mEq/L No ketones were detected in the urine. The patient was treated with intravenous fluids, sodium bicarbonate, insulin, and hemodialysis. All medications were discontinued. The acidosis resolved shortly after hemodialysis. The hospital course was complicated by the onset of atrial fibrillation occurring on day 2 that did not respond to chemical cardioversion. On day 6 the patient was discharged home with resolving acute renal failure and normal serum pH., Conclusions: The mortality rate of biguanide-induced lactic acidosis is approximately 50%; thus, early recognition and treatment are essential. Suspicion of lactic acidosis should be high when diabetic patients who are taking a biguanide present with acidosis. The majority of cases of metformin-induced lactic acidosis have occurred in patients with contraindications to the drug (i.e., renal dysfunction). Thus, it is important to maintain strict adherence to these contraindications and monitor patients for deteriorating renal function.

Objective: To determine whether salivary concentrations of ketoconazole and fluconazole may explain the apparent disparity between in vitro activity and clinical efficacy observed with these drugs., Design: Healthy subjects received a single oral dose of ketoconazole 400 mg or fluconazole 100 mg in a randomized, crossover fashion. Saliva was collected at 0, 1, 2, 3, 6, 12, and 24 hours. Blood samples were obtained at 2 and 24 hours. Salivary concentrations and plasma concentrations for each drug were determined by HPLC. Minimum inhibitory concentration (MIC) testing was determined in triplicate on 6 clinical isolates of Candida albicans, and times over the median MIC values were calculated., Participants: Eight subjects completed the study., Results: The mean (+/- SD) peak salivary concentration for ketoconazole was 0.119 +/- 0.050 microgram/mL at 3 hours; no subject had a detectable ketoconazole salivary concentration at 24 hours. At 2 and 24 hours, mean ketoconazole plasma concentrations were 7.64 +/- 3.87 and 0.11 +/- 0.05 microgram/mL, respectively. The saliva to plasma concentration ratio at 2 hours was 0.01. The mean peak salivary concentration of fluconazole was 2.56 +/- 0.34 microgram/mL at 3 hours. At 24 hours, the mean salivary concentration was 1.44 +/- 0.33 microgram/mL. At 2 and 24 hours, mean fluconazole plasma concentrations were 4.39 +/- 3.33 and 3.72 +/- 2.83 micrograms/mL, respectively. The saliva to plasma concentration ratio at 2 hours was 0.55. Median MIC values were 0.0625 microgram/mL (range 0.0313-0.125) for ketoconazole and 0.25 microgram/mL (range 0.125-0.5) for fluconazole. Calculated times over which ketoconazole and fluconazole exceeded the median MICs in saliva were approximately 13 and greater than 24 hours, respectively., Conclusions: After a single oral dose, fluconazole achieved higher salivary concentrations than did ketoconazole. This may explain the increased clinical efficacy of fluconazole in the treatment of oropharyngeal-esophageal candidiasis when compared with ketoconazole.

Objective: To discuss the in vitro activity, pharmacokinetics, clinical efficacy, adverse effects, and relative merits of loracarbef, a new orally administered carbacephem antibiotic., Data Sources: Pertinent literature was identified by a review of selected journals and a MEDLINE search. Additional information was provided by the manufacturer of loracarbef., Study Selection: All studies that have evaluated the clinical efficacy of loracarbef were included. In vitro studies were included if they used similar methodologies. Additional information was incorporated regarding the chemistry, pharmacokinetics, and adverse effects of loracarbef., Data Synthesis: Loracarbef has antibacterial activity against most community-acquired respiratory tract, skin and skin structure, and urinary tract pathogens. The drug is well absorbed after oral administration and plasma concentrations achieved in patients are greater than the in vitro minimum inhibitory concentrations for most of the above bacteria. Although the majority of the clinical studies with loracarbef have methodologic deficiencies, loracarbef therapy has demonstrated similar efficacy in the treatment of upper respiratory tract (except otitis media), lower respiratory tract, skin and skin-structure, and urinary tract infections compared with accepted antibiotics. Potential advantages of the new carbacephem may be improved patient compliance with its less frequent dosing schedule (once or twice a day, depending on the infection), and a low incidence of adverse effects., Conclusions: Preliminary data indicate that loracarbef may be an alternative agent for the treatment of a variety of community-acquired infections. Additional clinical experience and rigorously controlled comparative clinical trials are necessary to enable practitioners to fully define the therapeutic role of loracarbef.

Objective: To review the epidemiology of Haemophilus influenzae type b (Hib) disease, the first Hib vaccine and its limitations, the characteristics and clinical efficacy of the newer conjugate vaccines, and the current recommendations for administration of Hib vaccines., Data Sources: Pertinent literature was identified via a MEDLINE search. Additionally, references cited in published articles were used as data sources., Study Selection: Studies describing the epidemiology of Hib disease and the efficacy and/or immunogenicity of the Hib vaccines are reviewed., Data Synthesis: Serious invasive disease secondary to Hib infection causes significant morbidity and mortality in children between the ages of three months and five years. The original Hib vaccine was found to be ineffective in stimulating an adequate immune response in children younger than two years of age. The new Hib conjugate vaccines provide superior efficacy and immunogenicity compared with the original unconjugated vaccine. They stimulate an immune response that is distinctly different from that elicited by the original vaccine. Two vaccine products are currently licensed for use in children as young as two months of age, thus conferring immunity to those children at highest risk for Hib disease., Conclusions: The new Hib conjugate vaccines provide excellent efficacy and, when used as recommended, may significantly reduce the incidence of invasive Hib disease and its sequelae.

Objective: To discuss the potential of histamine H2-receptor antagonists (H2RAs) to cause malabsorption of vitamin B12 (cyanocobalamin)., Data Sources: Pertinent literature was identified via a MEDLINE search. Journals and references cited in published articles also were used as data sources., Study Selection: Studies evaluating the effect of H2RAs on vitamin B12 absorption were reviewed., Data Synthesis: H2RAs decrease acid secretion by the gastric parietal cells. Gastric acid and pepsin produced by these cells are required for the cleavage of vitamin B12 from dietary sources. Intrinsic factor (IF), also produced by gastric parietal cells, is required for vitamin B12 absorption from the gastrointestinal tract. Although H2RAs have not conclusively been shown to decrease IF secretion, studies have demonstrated a significant reduction in food-bound vitamin B12 absorption secondary to decreased acid secretion in patients taking these drugs., Conclusions: H2RAs have the potential to cause vitamin B12 deficiency. This may be important in patients with inadequate stores of vitamin B12 (e.g., poor diet), particularly those receiving H2RA therapy continuously for more than two years. Healthcare providers should be aware of this potential adverse effect.