Annals of Pharmacotherapy

Venturini, Francesca; Nichol, Michael B; Sung, Jennifer CY; Bailey, Karen L; Cody, Marisue; McCombs, Jeffrey S

doi: 10.1345/aph.18198pmid: 10200850

OBJECTIVE:To determine which factors affect compliance with sulfonylureas in a population served by a health maintenance organization in Southern California.METHODS:Retrospective analysis of pharmacy records and healthcare utilization data for two years (April 1993–March 1995), and a survey mailed to patients. Patients treated with sulfonylureas were selected for analysis on the basis of their prescription profile. Compliance was measured from the pharmacy records as the proportion of days the patient was in possession of the prescribed medications. Patient compliance with sulfonylureas was modeled as a function of four clusters of determinants: patient-related attributes, drug regimen characteristics and complexity, health status and disease-related variables, and characteristics of the interaction with healthcare providers.RESULTS:786 patients were identified for analysis (49.1% women, mean age 59 y). The mean compliance rate was 83% ± 22% SD. Compliance was significantly positively related with age and self-reported level of medication-taking compliance at baseline. Factors shown to have an inverse relationship with compliance were treatment complexity, perception of general health, and being a newly treated patient (adjusted R2 for the final model = 0.148).CONCLUSIONS:Our results suggest that factors found to be associated with noncompliant behavior (e.g., being a newly treated patient, self-reported compliance, regimen complexity) can be assessed by physicians and pharmacists as a routine practice.

McAlister, Finlay A; Ackman, Margaret L; Tsuyuki, Ross T; Kimber, Shane; Teo, Koon K

doi: 10.1345/aph.18195pmid: 10200851

OBJECTIVE:To define the contemporary practice patterns of digoxin utilization for the management of patients with atrial fibrillation (AF).METHODS:A retrospective medical records audit of 2490 patients with documented AF, from 12 Canadian hospitals and six outpatient clinics, during fiscal year 1993–1994, was conducted.RESULTS:There were 1158 women and 1332 men, with a mean age of 72 years; 956 patients were <70 years of age and 1534 were ≥70 years old. The majority of patients had nonvalvular AF (75% of those with a documented etiology). Paroxysmal AF (PAF) was documented in 800 patients, 936 had chronic AF, and 754 had new-onset AF. While the prescribing patterns were heterogeneous, the predominant strategy pursued in all subgroups appeared to be that of achieving rate control. Digoxin was the most commonly prescribed medication (79%) and was prescribed for the majority of patients in all subgroups, including patients with PAF (74%) and patients with a history of chronic AF who were currently in sinus rhythm (83%). Only 10% of the patients with PAF who were prescribed digoxin had congestive heart failure. Similarly, less than 25% of the patients with chronic AF who were prescribed digoxin after conversion to sinus rhythm had evidence of heart failure.CONCLUSIONS:In the absence of clinical trial evidence supporting either a strategy of antiarrhythmic therapy or rate control with anticoagulation, the appropriateness of the observed prescribing practices cannot be judged. However, digoxin is not the best rate-controlling agent for all patients and may be overused in certain subgroups of patients, such as those with PAF and those successfully converted to sinus rhythm.

Smith, Scott R; Boyd, Eddie L; Kirking, Duane M

doi: 10.1345/aph.18320pmid: 10200852

OBJECTIVE:To examine the strength of the associations between predisposing, enabling, and need-for-care variables and the self-treatment of HIV disease; and to compare sociodemographic and illness-related factors associated with the use of vitamins, nonprescription medications, herbs, and recreational substances among HIV-infected individuals.METHODS:Data were derived from 7887 interviews conducted as part of the AIDS Cost and Services Utilization Survey. The conceptual framework was the Andersen Behavioral Model of Health Services Use. Factors associated with nonprescription and alternative medication use were assessed using logistic regression. Generalized estimating equations were applied to adjust variance estimates for within-person correlations of drug use over time.RESULTS:After adjusting for perceived health status, T cell count, and stage of disease, the results indicated that African-Americans were less likely to use nonprescription drugs (odds ratio [OR] 0.65, 95% CI 0.52 to 0.81), vitamins (OR 0.59, 95% CI 0.48 to 0.73), and herbs (OR 0.41, 95% CI 0.22 to 0.76), compared with non-Hispanic whites. Similarly, Hispanics were less likely to report use of herbs (OR 0.58, 95% CI 0.34 to 0.98) or recreational drugs (OR 0.34, 95% CI 0.15 to 0.76) than were non-Hispanic whites. Oppositely, individuals who had a college education were more likely to use vitamins (OR 1.26, 95% CI 1.05 to 1.50) and herbs (OR 2.47, 95% CI 1.56 to 3.91). Enabling variables such as insurance status and income were generally associated only with use of recreational drugs. Need-for-care variables were generally associated only with use of nonprescription drugs and vitamins.CONCLUSIONS:Predisposing, enabling, and need-for-care variables from the Andersen Behavioral Model were significantly associated with the use of four categories of drugs to self-treat HIV disease. However, there was not a consistent pattern across the drug categories.

Smith, Joseph K; Aljazairi, Abdulrazaq; Fuller, Stephen H

doi: 10.1345/aph.18171pmid: 10200853

OBJECTIVE:To report a case of international normalized ratio (INR) prolongation in a patient receiving warfarin who experienced several episodes of diarrhea.CASE SUMMARY:A 56-year-old white woman, previously controlled on warfarin therapy (INR 2.5–3.5) after aortic valve replacement, experienced six episodes of INR elevation, each associated with an acute bout of diarrhea lasting from one to four days. The patient had not received additional warfarin or new medications (including nonprescription medications and herbal remedies) prior to the episodes. The patient had no obvious signs of bleeding (except bruising on 1 episode) or signs of infection determined through physician evaluation of the patient and her stools. In addition, she had no diagnosis of liver disease or acute or chronic malabsorption. The patient did report that her dietary intake decreased to 25–50% of normal during these episodes of diarrhea, which may result in decreased vitamin K ingestion.DISCUSSION:This is one of the first case reports documenting a trend of INR elevation specifically with episodes of diarrhea. Since most of the common reasons for acute INR elevation have been eliminated, diarrhea with decreased oral intake are the most probable causes for these observed changes in the INR. Several reports suggest that acute diarrhea results in malabsorption of vitamin K, which can predispose patients taking warfarin to INR elevations, but in many of these reports patients had other risk factors for INR elevation. Although the effect of diarrhea on vitamin K absorption and the INR is difficult to quantify, the INR elevation reported here seemed to be directly associated with the duration of each diarrheal episode.CONCLUSIONS:Diarrhea episodes in patients receiving warfarin can result in prolongation of the INR and possible bleeding. Patients who experience diarrhea or decreased oral intake resulting in elevated INRs should have their INRs evaluated more frequently and their warfarin doses adjusted appropriately.

Humma, Larisa M; Swims, Melanie P

doi: 10.1345/aph.18206pmid: 10200854

OBJECTIVE:To report the development of symptoms suggesting transient ischemic attacks during bupropion treatment for smoking cessation.CASE SUMMARY:A 67-year-old white man experienced paresthesia, dizziness, tinnitus, confusion, and gait impairment shortly after starting bupropion as an aid to smoking cessation. Bupropion was discontinued on hospital admission, and testing for vertebral basilar artery disease was negative. His symptoms resolved, and he remained asymptomatic until restarting bupropion two days after hospital discharge.DISCUSSION:Although separate case reports have reported sensory disturbances, tinnitus, and balance impairment associated with bupropion use, the combination of symptoms occurring in this patient has not been previously published.CONCLUSIONS:The temporal relationship between bupropion exposure and symptomatology suggests that bupropion caused symptoms mimicking transient ischemic attacks in this patient.

Budris, William A; Roxe, David M; Duvel, James M

doi: 10.1345/aph.18029pmid: 10200855

OBJECTIVE:To report a case of high anion gap metabolic acidosis related to infusion of aminocaproic acid (ACA) that temporarily corrected during hemodialysis and resolved upon ACA discontinuation.CASE SUMMARY:A 65-year-old white woman with staphylococcal sepsis complicated by acute renal failure was treated with ACA to control a hemorrhagic coagulopathy. After receiving an initial 5-g bolus of ACA, she received a continuous intravenous infusion of 500 mg/h for just over 5 days, then 250 mg/h for a final 12 hours. Immediately after beginning ACA therapy, she developed a severe anion gap metabolic acidosis that briefly improved after hemodialysis. The condition resolved completely only after the discontinuation of ACA and therapy with a systemic alkalinizer.DISCUSSION:ACA is not among the previously identified causes of high anion gap metabolic acidosis. The temporal profile relating anion gap to ACA initiation, hemodialysis treatment, and ACA discontinuation supports causality in this case. The magnitude of increase in the anion gap appears to have been proportional to the dose of ACA.CONCLUSIONS:In patients with renal impairment, ACA administration may produce a dose-related, high anion gap metabolic acidosis that might be reversible during hemodialysis. Insufficient data are available, but when ACA must be used in such patients, a more conservative dosing of ACA should be coupled with close monitoring.

Zaim, Sina; Wiley, David B; Albano, Shirley A

doi: 10.1345/aph.18214pmid: 10200856

OBJECTIVE:To report a possible association between naltrexone therapy and the development of rhabdomyolysis in one patient.CASE SUMMARY:A 28-year-old white man in good physical health was started on naltrexone 50 mg/d for inpatient treatment of alcohol dependence and depression. A routine serum chemistry panel obtained on day 9 of naltrexone therapy showed marked new elevations in creatine kinase and aspartate aminotransferase. The patient remained asymptomatic and did not develop renal insufficiency. The serum enzyme concentrations returned to normal within eight days of naltrexone discontinuation.DISCUSSION:Rhabdomyolysis has not been previously reported to occur in patients during treatment with naltrexone. Alcoholism may result in a reversible acute muscle syndrome, but our patient did not fit the appropriate clinical profile for such a syndrome. Additionally, the other prescribed medications could not be implicated as possible causative agents.CONCLUSIONS:This case report illustrates a possible association between naltrexone therapy and rhabdomyolysis.

Lalkin, Arieh; Kapur, Bhushan M; Koren, Gideon

doi: 10.1345/aph.18132pmid: 10200857

OBJECTIVE:To report an accidental contamination of antibiotic suspension by methadone that occurred in a retail Canadian pharmacy, leading to severe poisoning in a young child.CASE SUMMARY:A 4 1/2-year-old healthy Asian boy was prescribed amoxicillin suspension for cough and fever. Shortly after receiving the second dose of 5 mL he became drowsy and less responsive. On admission, he was arousable by deep pain, and pinpoint pupils were noted. A urine sample sent for a toxicology screen revealed the presence of methadone and its metabolite. Blood methadone concentrations were 0.23 and 0.14 mg/L, five and nine hours after the second dose of amoxicillin was given, respectively. The amoxicillin suspension was tested for methadone and was found to have a concentration of 2.4 g/L. The child gradually improved and was discharged on day 4 in good condition. The pharmacy in which the antibiotic was dispensed has been a dispensing center for a local methadone maintenance program, and methadone was accidentally mixed with the antibiotics.DISCUSSION:In this case, a near fatal outcome occurred when methadone was inadvertently mixed with antibiotics in a community pharmacy. A literature search revealed two previous reports of opiate toxicity in children following ingestion of oral antibiotic preparations.CONCLUSIONS:Prompt action is needed in Canadian pharmacies that dispense methadone in order to minimize such errors in the future. General practitioners, pediatricians, and emergency department physicians should recognize and suspect this rare cause of opiate toxicity in a child. In a patient presenting with a decreased level of consciousness and miosis, with or without respiratory depression, naloxone administration should be considered, whether or not a history of opioid ingestion is obtained.

Wooster, Melissa B; Luzier, Aileen B

doi: 10.1345/aph.18006pmid: 10200858

OBJECTIVE:To summarize the published data on reteplase, the most recent thrombolytic agent approved by the Food and Drug Administration for use in the management of acute myocardial infarction in adults.DATA SOURCES:Published data on reteplase identified by MEDLINE searches (January 1985–June 1997), as well as other pertinent literature.DATA SYNTHESIS:Reteplase is a new thrombolytic agent derived from human tissue plasminogen activator. Its mechanism of action is similar to that of alteplase, but it differs in pharmacokinetic and pharmacodynamic properties. Certain structural changes contribute to differences in pharmacokinetic properties such as a prolonged half-life (15 min), which allows it to be administered as two 10-MU bolus injections. Reteplase has been shown to have fibrin specificity similar to that of alteplase, but with a lower binding affinity for fibrin. This enables reteplase to bind to the thrombus repeatedly and increases its fibrinolytic potential. In clinical trials, reteplase demonstrated more rapid and complete coronary patency compared with alteplase, without a significant increase in clinical adverse events. However, the improvement in coronary artery patency with reteplase versus alteplase did not result in a reduction in mortality in the GUSTO III trial.CONCLUSIONS:Despite evidence that use of reteplase results in an improved coronary artery patency rate versus accelerated infusion alteplase, an improvement in mortality rate with reteplase was not shown. Reteplase may have an advantage over alteplase due to a more rapid and simpler dosing regimen, but the significance of this difference is yet to be determined.

Pai, Vinita B; Nahata, Milap C

doi: 10.1345/aph.18089pmid: 10200859

OBJECTIVE:To review the clinical pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of nelfinavir mesylate.DATA SOURCE:A MEDLINE search restricted to English-language literature from January 1966 to February 1998 and an extensive review of journals was conducted to prepare this article. MeSH headings included protease inhibitors, nelfinavir mesylate, and AG1343. Abstracts presented at meetings and data submitted to the Food and Drug Administration (FDA) were also reviewed.DATA EXTRACTION:The data on efficacy, pharmacokinetics, adverse effects, and drug interactions were obtained from in vitro studies, as well as open-label and controlled trials.DATA SYNTHESIS:Nelfinavir inhibits HIV protease enzyme resulting in formation of immature and noninfectious virions. In combination with nucleoside reverse transcriptase inhibitors, nelfinavir is effective in reducing the viral load below the quantifiable limit (<500 copies/mL) and increasing the mean CD4+ cell count. This antiviral effect is sustained at least over 21 months. The bioavailability of nelfinavir ranges from 20% to 80%, and it increases when nelfinavir is administered with food. Following multiple dosing of nelfinavir 750 mg three times daily, maximum concentration at steady-state was 3–4 μg/mL and minimum concentration was 1–3 μg/mL. The elimination half-life for nelfinavir ranges from three to five hours. Nelfinavir is primarily metabolized in the liver by the cytochrome P450 isoenzymes and excreted in the feces. Current dosing recommendations are 750 mg three times daily for adults and adolescents and 20–30 mg/kg/dose three times daily for children aged 2–13 years. Studies of twice-daily regimens in adults are being conducted and are promising. Use of nelfinavir as salvage therapy is also being studied. Some of the commonly reported adverse events of nelfinavir are diarrhea, nausea, vomiting, and abdominal pain.CONCLUSIONS:Despite the limited published data, the FDA has approved nelfinavir in combination therapy for the treatment of HIV infection. The choice of antiretroviral (ARV) regimens should be made based on the risk of disease progression as indicated by HIV RNA concentrations and CD4+ cell counts, patients' previous ARV experiences and responses, concomitant drug therapy, compliance history, underlying disease states, and adverse reaction history.