Annals of Pharmacotherapy

Tang, Ignatius Y; Cox, Donna S; Patel, Kruti; Reddy, Bharathi V; Nahlik, Linda; Trevino, Sharon; Murray, Patrick T

doi: 10.1345/aph.1E480pmid: 15632219

BACKGROUND:Argatroban, a direct thrombin inhibitor, is an effective anticoagulant for patients who have heparin-induced thrombocytopenia (HIT). Anticoagulation is usually required for renal replacement therapy (RRT).OBJECTIVE:To prospectively evaluate the pharmacokinetics, pharmacodynamics, and safety of argatroban during RRT in hospitalized patients with or at risk for HIT.METHODS:Five patients with known or suspected HIT underwent hemodialysis (n = 4) or continuous venovenous hemofiltration (CVVH, n = 1), while receiving a continuous infusion of argatroban 0.5–2 μg/kg/min. Activated partial thromboplastin times (aPTTs), activated clotting times (ACTs), argatroban concentrations (plasma, dialysate, CVVH effluent), and safety were assessed before, during, and after a 4-hour session of RRT. Systemic and dialytic argatroban clearances were calculated.RESULTS:Among the 4 hemodialysis patients, aPTT, ACT, and plasma argatroban concentrations remained stable during RRT, with respective mean ± SD values of 74.3 ± 34.2 seconds, 198 ± 23 seconds, and 499 ± 353 ng/mL before RRT, and 70.6 ± 21.4 seconds, 181 ± 12 seconds, and 453 ± 295 ng/mL 2 hours after starting RRT (p values NS). Systemic clearance was 17.7 ± 12.8 L/h before hemodialysis and 17.0 ± 9.5 L/h during hemodialysis (n = 2). The dialyzer clearance (dialysate recovery method) was 1.5 ± 0.4 L/h (n = 4). Generally similar responses occurred in the CVVH patient: systemic argatroban clearance was 4.8 L/h before CVVH and 4 L/h during CVVH. The hemofilter argatroban clearance was 0.9 L/h. No bleeding or thrombosis occurred.CONCLUSIONS:Argatroban provides effective alternative anticoagulation in patients with or at risk for HIT during RRT. Argatroban clearance by high-flux membranes during hemodialysis and CVVH is clinically insignificant, necessitating no dose adjustment.

Breekveldt-Postma, Nancy S; Herings, Ron MC

doi: 10.1345/aph.1E163pmid: 15598968

BACKGROUND:Controlled-release dosage forms may enhance persistence with therapy because of reduced dosing frequency and fewer adverse effects.OBJECTIVE:To assess the differences in persistent use of nifedipine between once-daily nifedipine gastrointestinal therapeutic system (GITS) and twice-daily nifedipine retard formulations.METHODS:Incident nifedipine users were selected from January 1992 to December 2001 from the PHARMO database, including drug-dispensing records and hospital records of more than one million subjects in the Netherlands. Patients with unaltered formulation and dosing frequency of nifedipine in the first year of follow-up with at least 2 prescriptions were included in the cohort. Persistence with different formulations was assessed using Cox's proportional hazard analyses. Covariates included in the analysis were, among others, hospitalizations and comedication for cardiovascular diseases.RESULTS:In total, 5889 incident users of nifedipine were included. The median duration of the first treatment episode was 133 days for nifedipine retard and 262 days for nifedipine GITS. One-year persistence with nifedipine increased from 32% in patients using retard formulations to 44% in patients using nifedipine GITS. Multivariate analyses showed that patients using nifedipine GITS were 1.3 times (RR 1.33; 95% CI 1.22 to 1.46) more persistent than those using retard formulations of nifedipine. Persistent patients more often used other antihypertensive drugs and were more often hospitalized for cardiovascular diseases.CONCLUSIONS:Patients using once-daily nifedipine GITS are more persistent with therapy than patients using twice-daily retard formulations.

Summers, Kelly M; Brock, Tina Penick

doi: 10.1345/aph.1E321pmid: 15613465

BACKGROUND:Osteoporosis-associated fractures burden both individuals and the overall healthcare system. Bone mineral density (BMD) screening remains the gold standard measure for identifying patients at risk.OBJECTIVE:To determine the impact of convenient, pharmacist-led BMD screening and counseling sessions on identification and education of patients at risk for or with osteoporosis.METHODS:Nonpregnant persons >18 years of age were eligible for enrollment in this descriptive study. At an urban retail pharmacy, participants underwent risk factor assessment, peripheral BMD scanning, and personalized counseling. At 3 and 6 months after screening, subjects were questioned by telephone regarding any subsequent primary care provider (PCP) interactions, as well as any behaviors initiated and/or medications modified.RESULTS:Of the 102 subjects screened, 22.6% and 11.7% were identified as being at medium risk (T score −1.0 to −2.5) and high risk (T score −2.5 or less) for osteoporosis, respectively. By 6 months, 42.5% of the participants reported increasing their dietary intake of calcium, 29.3% began or increased calcium supplements, and 54.9% positively modified smoking status, exercise level, alcohol consumption, or caffeine intake. Additionally, 24 of 52 subjects who had discussed their results with a PCP by 6 months also received a treatment recommendation. Eighty-nine participants reported the community location increased their likelihood of receiving a BMD scan.CONCLUSIONS:Overall, pharmacist-led BMD screenings that include individualized counseling sessions appear convenient, accessible, and beneficial for patients. With the establishment of clinical benefit of and positive reception to such screenings, pharmacists can now look toward securing consistent reimbursement for this vital pharmaceutical care service.

Sansgiry, Sujit S; Pawaskar, Manjiri D

doi: 10.1345/aph.1E494pmid: 15644473

BACKGROUND:Over-the-counter (OTC) medication packages are important sources of information forconsumers during product selection and use. Consumers may not be able to accessinformation from OTC packages if external tags, namely price or anti-theft tags, areimproperly placed.OBJECTIVE:To determine the amount and type of information concealed by anti-theft tags and pricetags affixed on OTC drug packages.METHODS:A field study was performed by evaluating packages containing acetaminophen andcombinations of acetaminophen in stores located in Houston. Five packages for 4 productsselected from each store after an initial survey for presence of an external tag wereexamined. A data collection sheet was prepared that extracted the type and amount ofinformation concealed by these tags. Data were analyzed by performing descriptiveanalyses to provide an understanding of the information obscured.RESULTS:A total of 24 stores were considered in the study, and 67 products and 285 packageswere evaluated. External tags, both anti-theft and price tags, obscured significantamounts of information on the principal display panel (53.4%) and the Drug Facts panel(47.7%) of OTC packages. These tags concealed crucial information on various aspects oflabels such as brand names (42.3%), product description (36.3%), warnings (51.5%), uses(10.4%), and purposes (7.2%).CONCLUSIONS:Results suggest that improper use of external tags clearly obscured importantinformation on OTC medication packages necessary for consumers to make informeddecisions regarding product selection and use. Tagging practices should be altered toallow consumers full access to drug information on the product.

Sheth, Heena S; Verrico, Margaret M; Skledar, Susan J; Towers, Adele L

doi: 10.1345/aph.1E361pmid: 15644479

BACKGROUND:Prochlorperazine and droperidol were commonly used antiemetics at the University of Pittsburgh Medical Center– Presbyterian Hospital until a shortage of prochlorperazine occurred and a black box warning was added to droperidol prescribing information. Subsequently, promethazine was selected as the approved intravenous antiemetic for therapeutic interchange in December 2001. Promethazine use and adverse drug events (ADEs) were investigated following review of a serious ADE that identified promethazine use as a probable contributing factor.OBJECTIVE:To illustrate ADEs associated with promethazine and characterize high-risk patients.METHODS:An ADE database analysis identified promethazine ADEs reported from 2000 to 2003. Promethazine utilization and ADEs were compared with those of other antiemetics during the pre- and post-interchange periods.RESULTS:Promethazine utilization increased significantly during the post-interchange period compared with all other antiemetics (p < 0.001). Promethazine ADEs increased from one event during the pre-interchange period to 13 events during the post-interchange period. Causality assessment using the Naranjo algorithm ranged from possible to probable. The promethazine ADE rate per 10 000 doses was significantly higher than the combined ADE rate for all other antiemetics (p < 0.001; incident rate ratio [IRR] 4.32). Elderly patients (aged ≥65 y) experienced more promethazine ADEs than younger patients (p = 0.005; IRR 4.68). Concurrent use of opioids and/or sedating drugs contributed to promethazine ADEs in 11 of 14 (78.6%) patients.CONCLUSIONS:Geriatric status is a significant risk factor for promethazine ADEs. Concomitant use of sedating drugs may further increase the risk for ADEs. Therapeutic interchange programs should be monitored for both ADEs and utilization.

Levy, Howard; Small, David; Heiselman, Darell E; Riker, Richard; Steingrub, Jay; Chen, Ruqin; Qualy, Rebecca L; Darstein, Christelle; Mongan, Ellen

doi: 10.1345/aph.1E386pmid: 15632220

BACKGROUND:Drotrecogin alfa (activated) [DrotAA] is approved for the reduction of mortality in adults with severe sepsis (sepsis with acute organ dysfunction) and high risk of death. Patients whose actual body weight was >135 kg were excluded from the Phase III PROWESS trial.OBJECTIVE:To compare exposure to DrotAA in patients with severe sepsis weighing >135 kg with those weighing ⩽135 kg in an open-label, Phase IV trial, and quantify the elimination half-life (t1/2) of DrotAA in these patients.METHODS:PROWESS inclusion/exclusion criteria were used, except that patients >135 kg were enrolled. Blood samples were collected for steady-state plasma concentration (Css) analysis of activated protein C once each day and for t1/2 analysis after infusion. Weight-normalized clearance (Clp) and t1/2 estimates for DrotAA were calculated and compared between weight groups.RESULTS:Patient weight range was 59–227 kg. There were 32 patients ⩽135 kg and 20 patients >135 kg enrolled. Median Clp was 0.45 L/h/kg (interquartile range [IQR] 0.37–0.54) for patients ⩽135 kg and 0.42 L/h/kg (IQR 0.33–0.54) for patients >135 kg (p = 0.692). Median estimates of Css were 51.9 ng/mL (IQR 43.4–62.0) and 56.5 ng/mL (IQR 44.9–71.1; p = 0.570). In patients ⩽135 kg, DrotAA had a median t1/2 of 16.7 minutes (IQR 13.9–20.0) compared with 16.0 minutes (IQR 12.9–19.8) in patients >135 kg (p = 0.767), for a composite median t1/2 of 16.3 minutes (IQR 14.2–18.8).CONCLUSIONS:There is no statistically significant difference in Css concentrations or t1/2 of DrotAA between patients weighing ⩽135 kg and >135 kg. DrotAA should be dosed by actual body weight.

Oborne, C Alice; Luzac, Michal L

doi: 10.1345/aph.1D160pmid: 15644485

BACKGROUND:In the UK, medicines are being reclassified from prescription-only drugs to allow supply without prescription. This allows faster and easier access to medicines to treat minor ailments and allows patients to take greater responsibility for their health. However, over-the-counter (OTC) drugs may pose risks to patients; thus, it is important to understand patients' OTC medicine use.OBJECTIVE:To assess use of OTC drugs prior to and during hospital stay of inpatients of all ages and specialties.METHODS:Data were collected for 186 randomly selected patients. Patients were interviewed about OTC medicine use. Clinical notes and drug charts were examined for documentation of OTC medicine use.RESULTS:A total of 268 OTC medicines were used by 119 (64.0%) patients, and 117 (43.7%) were taken at least daily. Only 13 (4.9%) OTC drugs were recorded in the drug history taken at admission. Twenty-six (9.7%) OTC agents were still taken during hospitalization, but only 8 (31%) were recorded on drug charts. Patients bought 183 (68.3%) items from pharmacies, 28 (10.4%) in health food shops, and 57 (21.7%) elsewhere including supermarkets, homeopaths, or mail order. Patients had little knowledge of potential adverse effects or contraindications.CONCLUSIONS:Many patients use OTC medication prior to and during hospital stay, but documentation in hospital notes is poor. Healthcare professionals must pay closer attention to patients' use of OTC drugs.

Buckner, Kaitlin D; Chavez, Mary L; Raney, Erin C; Stoehr, James D

doi: 10.1345/aph.1E433pmid: 15644475

BACKGROUND:Many pregnant women use dietary supplements during pregnancy; however, relatively scant information is available on the safety of these products. Consumers of dietary supplements often rely on employees of health food stores to provide recommendations.OBJECTIVE:To evaluate recommendations made by health food store employees in the Phoenix metropolitan area regarding treatment of nausea/vomiting and migraines during pregnancy.METHODS:Phone calls were made by a disguised shopper to 155 health food stores in the greater Phoenix area. The caller posed as a woman 8 weeks' pregnant asking for recommendations for treatment of nausea/vomiting and migraines. Responses and recommendations were recorded and then compared with current scientific evidence obtained during a search of the literature using MEDLINE (1966–September 2004) as to whether or not the supplements and the methods of their use during pregnancy were contraindicated.RESULTS:Eighty-nine percent of stores offered recommendations for nausea/vomiting, and 82% provided recommendations for migraines. The use of ginger was the most recommended therapy for nausea/vomiting. Only 3.6% of respondents recommended correct usage, but failed to supply the correct dosage and duration. A total of 15 of 278 (5%) recommendations, for both nausea/vomiting and migraines, were for products contraindicated in pregnancy.CONCLUSIONS:In light of the increased use of dietary supplements by women during pregnancy, the willingness of personnel in health food stores to make any recommendations should foster concerns by patients and healthcare providers alike. Use of dietary supplements contraindicated in pregnancy could cause significant harm to the mother and/or fetus. Studies are needed to address the need for more stringent guidelines regarding health food stores and their recommendations.

Trissel, Lawrence A; Zhang, Yanping

doi: 10.1345/aph.1E408pmid: 15613463

BACKGROUND:Palonosetron HCl is a selective 5-HT3 receptor antagonist used for the prevention of chemotherapy-induced nausea and vomiting. Palonosetron HCl may be administered with other drugs by Y-site administration, including doxorubicin HCI and epirubicin HCI. Consequently, stability and compatability information are needed to verify the acceptability of such Y-site administration.OBJECTIVE:To evaluate the physical and chemical stability of undiluted palonosetron HCl 50 μg/mL with doxorubicin HCl 1 mg/mL and epirubicin HCl 0.5 mg/mL during simulated Y-site administration.METHODS:Triplicate samples of palonosetron HCl with each of the anthracycline chemotherapy drugs were tested. Samples were stored and evaluated for up to 4 hours at room temperature near 23°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 admixtures were clear and red—orange when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and remained low throughout the study. The drug concentration was unchanged in any of the samples throughout the study.CONCLUSIONS:Palonosetron HCl is physically and chemically stable with doxorubicin HCl and epirubicin HCl during simulated Y-site administration of these drugs over 4 hours at ambient room temperature.

Pakyz, Amy L

doi: 10.1345/aph.1E407pmid: 15598963

OBJECTIVE:To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions and precautions, and dosing recommendations of rifaximin, a new nonabsorbed antimicrobial agent for travelers' diarrhea.DATA SOURCES:A MEDLINE search (1966–July 2004) was conducted to extract human and animal research data in the English language on rifaximin.STUDY SELECTION AND DATA EXTRACTION:Randomized, double-blind, placebo-controlled trials were reviewed and included to evaluate the efficacy of rifaximin in the treatment of travelers' diarrhea.DATA SYNTHESIS:Rifaximin is approved for the treatment of travelers' diarrhea in patients ≥12 years of age with diarrhea caused by noninvasive strains of Escherichia coli. Rifaximin was superior to placebo and trimethoprim/sulfamethoxazole and equivalent to ciprofloxacin in the primary clinical endpoint of the time to the last unformed stool passed.CONCLUSIONS:Rifaximin is a viable alternative to ciprofloxacin for the treatment of travelers' diarrhea. As rifaximin is not systemically absorbed, it offers the advantage of leading to the development of less resistance compared with systemically absorbed antibiotics, in addition to fewer systemic adverse effects and drug interactions. However, the potential for cross-resistance between rifaximin and rifampin, as well as with other classes of antibiotics, is of concern and needs to be elucidated.