Annals of Pharmacotherapy

Gora-Harper, Mary Lea; Record, Kenneth E; Darkow, Theodore; Tibbs, Phillip A

doi: 10.1345/aph.10340pmid: 11724076

BACKGROUND:Ketorolac's efficacy as a postoperative analgesic has been shown to be comparable to that of narcotic analgesics, but with significantly fewer narcotic-related adverse events.OBJECTIVE:To assess whether the choice of postoperative analgesic, narcotic or ketorolac, has an impact on healthcare resource utilization and cost during inpatients' recovery period.DESIGN:Retrospective, multicenter, controlled, parallel, cost-minimization analysis.SETTING:Six US teaching hospitals.PATIENTS:This study included 559 patients that underwent either a spine or joint procedure and received adequate doses of narcotic (n = 284 of either morphine or meperidine) or ketorolac (n = 275).MEASUREMENTS:Time to reach recovery milestones, average utilization of healthcare resources, and average per-case postoperative treatment cost.RESULTS:Several recovery milestones, including time to first bowel movement, first oral intake, and first unassisted ambulation, were reached sooner in the ketorolac group, with a resultant shorter mean length of postoperative stay (narcotic 3.78 d, ketorolac 2.80 d; p = 0.01). Total per-patient cost of treatment was 32% greater in the narcotic group, resulting primarily from higher costs associated with hospitalization.CONCLUSIONS:Despite the higher acquisition cost of medication, healthcare resource utilization and total per-patient cost of treatment were lower for patients in the ketorolac group compared with patients in the narcotic analgesic study group. The majority of patients in the ketorolac group were also given concurrent narcotic analgesics; therefore, the beneficial effects observed may be secondary to the combination of ketorolac and narcotic analgesics.TRASFONDO:La eficacia de ketorolac como agente analgésico postoperatorio se ha demostrado que es comparable a la de los analgésicos narcóticos pero con significativamente menos eventos adversos relacionados con el efecto narcótico.

Robinson, Renee F; Nahata, Milap C

doi: 10.1345/aph.10354pmid: 11724077

OBJECTIVE:To determine the safety of gentamicin administered intravenously as a bolus.METHODS:All patients (n = 123, ages: up to 18y, 121; 21y, 1; 31y, 1) who received gentamicin intravenously as a bolus over a four-month period were studied retrospectively. Patient demographics, type of infection, dosing regimen, length of therapy, peak and trough serum concentrations, blood urea nitrogen, serum creatinine, and urine output were reviewed. Patients were stratified into four groups and data analyzed statistically.RESULTS:Mean initial dose (5.32 ± 2.38 mg/kg/d) was consistent with established guidelines for age and kidney development, with subsequent adjustments based on serum concentrations. Susceptible organisms were eradicated with a mean length of therapy of 6.9 ± 6.9 days (range 1–35). Patients received a median of nine doses: 42% received doses every eight hours and 33% received doses every 24 hours. No relationship between dosing and abnormal serum creatinine were found (p = 0.69). The estimated cost savings mainly from less nursing time and lower equipment and supply use were $50/patient with bolus administration of gentamicin.CONCLUSIONS:Intravenous bolus administration was safe in pediatric patients and was associated with lower costs.

Peloquin, Charles A; Zhu, Min; Adam, Rodney D; Singleton, Michael D; Nix, David E

doi: 10.1345/aph.1A088pmid: 11724078

OBJECTIVE:To determine the pharmacokinetics and relative bioavailability of para-aminosalicylic acid (PAS) granules.DESIGN:Phase I pharmacokinetics study.SETTING:University of Arizona School of Pharmacy.PARTICIPANTS:Sixteen healthy male and female volunteers aged 36 ± 8 years.INTERVENTIONS:Subjects received single doses of PAS granules (6 g) combined with cycloserine 500 mg, clofazimine 200 mg, ethionamide 500 mg, and pyridoxine 100 mg. Drugs were given on an empty stomach after an overnight fast (reference) with high-fat food, with orange juice, and with antacids.MEASUREMENTS AND RESULTS:Four subjects did not complete all four treatments due to adverse events or personal reasons. Plasma and urine samples were collected for 48 hours and measured by a validated HPLC assay. Pharmacokinetic data analysis was performed with WinNonlin using noncompartmental methods and a one-compartmental model. Bioequivalence testing was performed using the mean ratios of the maximum concentrations (Cmax) and AUC0-∞ of PAS, with 90% confidence intervals. Compared with the fasted condition, food increased Cmax 1.5–fold and AUC0-∞ 1.7-fold, and it doubled the time to maximum concentration (tmax). The least-squares mean ratios (treatment/reference) for Cmax were 0.90 (58% to 139% CI), 1.16 (75% to 179% CI), and 0.82 (52% to 127% CI) with orange juice, food, or antacid treatment, respectively. Corresponding ratios for AUC0-∞ were 1.05 (71% to 155% CI), 1.52 (103% to 224% CI), and 0.84 (57% to 125% CI), respectively.CONCLUSIONS:Food significantly enhanced the absorption of PAS, while orange juice and antacids had minor effects.

Shilo, Lotan; Hadari, Ruth; Kovatz, Susy; Qasim, Mahmud; Shenkman, Louis

doi: 10.1345/aph.10402pmid: 11724079

BACKGROUND:Nitrates are one of the most commonly prescribed drug groups for cardiac disease, especially for angina pectoris and congestive heart failure. The chronic efficacy of nitrates is limited by the development of tolerance, which can be attenuated by use of sustained-release preparations or administration of regular-release preparations asymmetrically.OBJECTIVE:To determine whether patients receiving isosorbide 5-mononitrate (ISMN) use the drug in a pharmacologically appropriate manner and whether they had been instructed in the prophylactic use of sublingual nitrates prior to effort.METHODS:We administered a questionnaire regarding details of nitrate use to 229 patients with ischemic heart disease using oral ISMN, prescribed prior to their current admission. The study was conducted in a 600-bed university-affiliated hospital.RESULTS:We found that only 15% of patients receiving regular-release ISMN were taking the drug asymmetrically. In contrast, 82.6% of the patients receiving sustained-release ISMN were using the drug properly. Only 38.1% of the patients treated with regular-release ISMN were treated with the dose recommended in the literature. Furthermore, of the 190 patients who reported experiencing effort angina, only 17.9% had been instructed in the prophylactic use of nitrates prior to effort.CONCLUSIONS:The majority of patients (85%) using regular-release ISMN were taking the medication in an inappropriate fashion, while most patients taking sustained-release preparations were using them properly. More than half the patients treated with regular-release ISMN were treated with doses exceeding the recommended dose. In addition, most patients experiencing effort angina had not been instructed regarding the prophylactic use of nitrates. These findings suggest that both physicians and pharmacists must be reminded of the continuing need to properly counsel patients regarding appropriate drug use.TRASFONDO:Los nitratos representan uno de los grupos de medicamentos que más se prescriben para enfermedad cardíaca, especialmente angina de pecho e insuficiencia cardíaca congestiva. La eficacia crónica de los nitratos está limitada por el desarrollo de tolerancia, la cual puede ser atenuada mediante el uso de preparaciones de liberación sostenida o la administración asimétrica de preparaciones de liberación regular.

Westerlund, LO Tommy; Marklund, Bertil RG; Handl, Wolfgang HA; Thunberg, Margareta E; Allebeck, Peter

doi: 10.1345/aph.1A065pmid: 11724080

OBJECTIVE:To document the number and types of drug-related problems (DRPs) identified in customers purchasing nonprescription products in Swedish pharmacies; describe the distribution of DRPs by customer's gender, age, underlying ailment, and class of drug; determine whether problems are identified to the same extent in pharmacies with staffed nonprescription self-service departments as in pharmacies with over-the-counter sales; and document the number and types of pharmacy interventions to prevent or resolve DRPs, including reasons for drug switches and referrals to physicians.METHODS:A computerized instrument for documentation of DRPs and pharmacy interventions was developed. The study was conducted in 45 volunteer pharmacies in Sweden during 10 weeks in late 1999.RESULTS:A total of 1425 problems and 2040 interventions were recorded by 308 pharmacy practitioners. Relatively fewer DRPs were documented in pharmacies with self-service departments. The most common DRPs were uncertainty about the indication for the drug (33.5%) and therapy failure (19.5%). Dyspepsia was the most frequently specified symptom (11.4%). Consumers of dermatologic products had significantly higher rates of problems than expected in relation to sales volume. The most common ways of responding to a problem were with consumer drug counseling (61.1%), switching of drugs (43.9%), and referral to a physician (27.5%).CONCLUSIONS:The study has demonstrated a need for more professional attention and intervention by pharmacy staff to prevent and rectify DRPs in nonprescription consumers. It seems especially important to make sure that consumers receive the appropriate drugs for their current ailments.

Al Khaja, Khalid AJ; Sequeira, Reginald P; Mathur, Vijay S

doi: 10.1345/aph.10399pmid: 11724081

OBJECTIVE:To determine drug prescription patterns and the extent of conformity with World Health Organization/International Society of Hypertension (WHO/ISH) guidelines in diabetic hypertension.DESIGN:Retrospective prescription-based survey.SETTING:Seven primary-care health centers, comprising approximately one-third of primary-care health centers in Bahrain.PATIENTS:Patients with type 2 diabetes and hypertension.MAIN OUTCOME MEASURE:The prescribing pattern of antihypertensive and antidiabetic drugs.RESULTS:Among a study sample of 1463 patients with type 2 diabetes and hypertension, antidiabetic agents were prescribed as monotherapy in the following descending order: glyburide, gliclazide, insulin, and metformin. As combinations, sulfonylureas plus metformin was most popular, followed by metformin plus insulin, and sulfonylureas plus insulin. Sulfonylurea and metformin with insulin was rarely used. There was no significant difference in prescribing of glyburide and metformin between the elderly and young middle-aged diabetic patients; many patients older than 65 years were treated with a β-blocker along with a long-acting sulfonylurea. Both as monotherapy and in overall use, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium-channel blockers were most often prescribed. Among 35.5% patients treated with antihypertensive combinations, various two- and three-drug combinations of β-blockers, ACE inhibitors, calcium-channel blockers, and diuretics were often used. The proportion of patients taking atenolol 100 mg/d was higher with combination regimens. Hydrochlorothiazide 25 mg or equivalent thiazide diuretics were extensively used.CONCLUSIONS:The prescribing pattern of antihypertensives in diabetic hypertension differs in many instances from WHO/ISH guidelines, especially regarding the choice of antihypertensive drugs and their combinations. The appropriateness of antidiabetic drug choice is questionable in relation to the antihypertensive used.

Zhang, Yanping; Trissel, Lawrence A

doi: 10.1345/aph.1A150pmid: 11724082

OBJECTIVE:To evaluate the physical and chemical stability of piperacillin sodium 3 and 4 g/100 mL and ticarcillin disodium 3 g/100 mL each admixed in NaCl 0.9% injection packaged in AutoDose Infusion System bags.DESIGN:Triplicate test samples of the penicillin antibiotics in NaCl 0.9% injection were packaged in ethylene vinyl acetate (EVA) plastic containers, AutoDose bags, designed for use in the AutoDose Infusion System. Samples were stored protected from light and evaluated at appropriate intervals for up to seven days at 23 °C and up to 30 days at 4 °C. Physical stability was assessed using turbidimetric and particulate measurement as well as visual inspection. Chemical stability was assessed by HPLC.RESULTS:All of the penicillin admixtures initially were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and exhibited little change in the ticarcillin disodium samples throughout the study. The piperacillin sodium samples exhibited small increases in measured haze throughout the study, but no accompanying increase in particulates ≥1.04 μm was found. All samples were essentially colorless throughout the study. HPLC analysis found some decomposition in the samples. Piperacillin sodium exhibited a 9–10% loss after five days at 23 °C. In the samples stored at 4 °C, piperacillin sodium exhibited acceptable stability through 21 days of storage, but losses exceeded 10% after 30 days. Ticarcillin disodium exhibited a 7% loss after three days, but 14% after five days at 23 °C. Less than 7% loss occurred after 21 days, but 12% loss after 30 days at 4 °C.CONCLUSIONS:Piperacillin sodium and ticarcillin disodium exhibited physical and chemical stability consistent with previous studies on these drugs. The AutoDose Infusion System bags were not found to adversely affect the physical and chemical stability of these penicillin antibiotics.

Hagmeyer, Kathleen O; Stein, Jenny

doi: 10.1345/aph.10239pmid: 11724083

OBJECTIVE:To report a severe episode of pruritus and elevated serum transaminases in a patient who was receiving carvedilol.CASE SUMMARY:A 40-year-old white man who had been taking carvedilol for the treatment of cardiomyopathy presented to the emergency department with pruritus over his entire body. Laboratory tests showed elevated serum transaminases. Carvedilol was discontinued and the patient received hydroxyzine hydrochloride to relieve symptoms. Liver function test results returned to normal in three weeks. Approximately one year later the patient was started on metoprolol and within 10 days again developed pruritus. The patient was told to discontinue the metoprolol immediately. At the time the metoprolol was stopped the liver function test results were normal.DISCUSSION:To the best of our knowledge, the adverse reaction presented in this case report is rare. The etiology of this adverse reaction remains unknown but suggests a possible adverse reaction that may recur if the patient is switched to another β-adrenergic blocker. The liver function test abnormalities appear to return to normal on discontinuation of carvedilol.CONCLUSIONS:Carvedilol may cause pruritus and elevated liver function test results. This reaction may recur if the patient is changed to an alternative β-adrenergic blocker. Patients taking carvedilol should be monitored for signs and symptoms of hepatotoxicity. If elevated liver function test results are noted, carvedilol should be discontinued.

Gilbar, Peter J; Brodribb, T Robert

doi: 10.1345/aph.1A051pmid: 11724084

OBJECTIVE:To report a probable drug interaction between phenytoin and fluorouracil.CASE REPORT:A 66-year-old white man started adjuvant chemotherapy for colon cancer with weekly bolus injections of fluorouracil and leucovorin calcium. He had been taking phenytoin 300 mg/d for epilepsy for more than four years. Eleven weeks later, the patient was reported to be unsteady on his feet and had fallen several times. The serum phenytoin concentration at that time was 36 μg/mL. The phenytoin dosage was decreased and the symptoms resolved. Phenytoin concentrations were monitored and the dosages were adjusted accordingly throughout the remaining 15 weeks of treatment with fluorouracil. After completion of chemotherapy, the phenytoin dose was gradually increased to the original dose with no signs of toxicity.DISCUSSION:Phenytoin is principally metabolized by CYP2C9. Inhibition of that isoenzyme by fluorouracil, and possible interference with its synthesis, appears to be the most likely cause of this interaction. The reduction in saturating substrate concentration of phenytoin was reduced as a result of this interaction, thus causing decreased clearance and increased serum concentrations. No previous interaction between phenytoin and fluorouracil has been reported. Both phenytoin and warfarin are metabolized by CYP269 and therefore exhibit the same spectrum of interactions when that isoenzyme is inhibited. Interactions have been reported with concurrent administration of warfarin and fluorouracil.CONCLUSIONS:The nature and extent of this phenytoin—fluorouracil interaction should be elucidated by in vitro investigations and a prospective study. Until then, clinicians should be aware of this potentially serious drug interaction and monitor patients closely for phenytoin toxicity.

Pollak, P Timothy; Mukherjee, Som D; Fraser, Albert D

doi: 10.1345/aph.1Z431pmid: 11724085

OBJECTIVE:To report a case of hypoglycemia that occurred in a patient treated with the selective serotonin-reuptake inhibitor, sertraline.CASE SUMMARY:An 82-year-old white woman with mild cardiovascular disease and no history of glucose intolerance was seen in the emergency department for a presyncopal episode associated with a blood glucose of 32 mg/dL as measured by the ambulance attendant. She had similar symptoms the day before. Despite repeated administration of oral and intravenous glucose, the patient had recurrent episodes of hypoglycemia and was hospitalized for four days. She had started taking sertraline 50 mg once daily for mild depression 25 days prior to presentation. Other medications included furosemide 20 mg/d, ramipril 5 mg/d, clopidogrel 75 mg/d, nitroglycerin patch 0.4 mg/h, and lorazepam 1 mg taken occasionally for agitation. She had never been prescribed any oral hypoglycemic agents. Serum sertraline and desmethylsertraline concentrations measured two, three, and four days after discontinuing sertraline were within the expected range, but the rate of decline was consistent with a moderately prolonged half-life.DISCUSSION:Sertraline has been shown to blunt postprandial hyperglycemia in rats and to potentiate the hypoglycemic effects of sulfonylurea agents in humans. It has not been reported to cause hypoglycemia independently, but in this case, a nondiabetic patient experienced multiple episodes of hypoglycemia that resolved after discontinuation of sertraline.CONCLUSIONS:This report and another implicating fluoxetine in a case of hypoglycemia suggest that healthcare professionals should consider these medications among the possible causes of hypoglycemia occurring in patients receiving selective serotonin-reuptake inhibitors.