Annals of Pharmacotherapy

To determine the number of cases of statin-associated rhabdomyolysis reported to the Food and Drug Administration for 6 statins and to profile the cases.

A retrospective analysis of all domestic and foreign reports of statin-associated rhabdomyolysis between November 1997 and March 2000 was conducted. Outcome measures included the total number of reports (initial plus follow-up), the number of unique cases, age, gender, percentages of report codes and role codes, and frequencies of concomitant interacting drugs that may have precipitated rhabdomyolysis, outcomes codes, and report source codes.

There were 871 reports of statin-associated rhabdomyolysis in the 29-month time frame examined, representing 601 cases. The following number of cases were associated with each of the individual statins: simvastatin, 215 (35.8%); cerivastatin, 192 (31.9%); atorvastatin, 73 (12.2%); pravastatin, 71 (11.8%); lovastatin, 40 (6.7%); and fluvastatin, 10 (1.7%). Drugs that may have interacted with the statins were present in the following number of cases: mibefradil (n = 99), fibrates (n = 80), cyclosporine (n = 51), macrolide antibiotics (n = 42), warfarin (n = 33), digoxin (n = 26), and azole antifungals (n = 12). The reports of 62.1% of cases were classified as expedited. Statins were designated as the primary suspect in 72.0% of the cases. Death was listed as the outcome in 38 cases. The majority of reports (n = 556) were from health professionals.

Compared with the other statins, simvastatin and cerivastatin were implicated in a relatively higher number of reports. Because of the various limitations of a spontaneous reporting-system database, caution is urged when interpreting the relative number of cases reported.

To provide a historical perspective on the origin and similarity of the “ideal” body weight (IBW) equations, and clarify the terms ideal and lean body weight (LBW).

Primary and review literature were identified using MEDLINE (1966–November 1999) and International Pharmaceutical Abstracts (1970–November 1999) pertaining to ideal and lean weight, height–weight tables, and obesity. In addition, textbooks and relevant reference lists were reviewed.

All articles identified through the data sources were evaluated. Information deemed to be relevant to the objectives of the review were included.

Height–weight tables were generated to provide a means of comparing a population with respect to their relative weight. The weight data were found to correlate with mortality and resulted in the use of the terms desirable or ideal to describe these weights. Over the years, IBW was interpreted to represent a “fat-free” weight and thus was used as a surrogate for LBW. In addition, the pharmacokinetics of certain drugs were found to correlate with IBW and resulted in the use of IBW equations published by Devine. These equations were consistent with an old rule that was developed from height–weight tables to estimate IBW. Efforts to improve the IBW equations through regression analyses of height–weight data resulted in equations similar to those published by Devine.

The similarity between the IBW equations was a result of the general agreement among the various height–weight tables from which they were derived. Therefore, any one of these equations may be used to estimate IBW.

To develop practical recommendations for the use of low-molecular-weight heparins (LMWHs) as prophylaxis and treatment of venous thromboembolism and acute coronary syndromes in patients with impaired renal function or obesity.

Multiple MEDLINE searches were performed (November 2008) to identify studies for inclusion, using a comprehensive list of search terms including, but not limited to, LMWH, enoxaparin, dalteparin, tinzaparin, obesity, weight, renal, kidney, elderly, monitoring, and anti-Xa.

Only articles published in English that were relevant for this review were included.

In the majority of patients, standardized prophylaxis or treatment doses of LMWHs can be used without the need for monitoring and adjusting regimens. For patients with severe renal impairment (estimated creatinine clearance [CrCl] <30 mL/min), doses of some LMWHs should be adjusted or unfractionated heparin should be used instead. CrCl should be estimated using the Cockcroft-Gault method. Differences are noted in the degree of accumulation of various LMWHs in patients with moderate-to-severe renal impairment, and thus, the degree of dose adjustment may differ among the various LMWHs. Increasing the prophylactic doses of LMWH may be appropriate in morbidly obese patients (body mass index ≥40 kg/m²). The use of total body weight is appropriate for therapeutic doses of LMWH in obese patients. Laboratory monitoring of the anticoagulation effect of LMWHs is generally not necessary, but should be considered in patients with morbid obesity (weight >190 kg), those with severe renal impairment, and those with moderate renal impairment with prolonged (>10 days) LMWH use. When anti-Xa activity is monitored, it should be determined using a chromogenic method and a calibration curve based on the LMWH used.

Additional data are needed for specific dose guiding in obese and renally impaired patients, who are often excluded from larger clinical trials. Practice recommendations are made based on available evidence and authors' clinical opinions.

More elderly patients affected by severe and chronic diseases are treated in primary care. Reports on the use of prescription drugs by the general elderly population are scarce, and more investigations are needed to optimize pharmaceutical care for these patients.

To analyze prescription drug use, diagnoses, and healthcare utilization among noninstitutionalized elderly patients.

Retrospective cohort study.

All people ±65 years old (n = 4642) living in the community of Tierp, Sweden, in 1994 were included. Prescription drug use and healthcare utilization have been registered for all inhabitants of the community since 1972. Information about filled prescriptions and diagnoses were obtained from a computerized research register.

Prescription drug use was high among the elderly (78%); the most used pharmacologic groups were cardiovascular, nervous system, and gastrointestinal medications. Women used more prescription drugs than men (average 4.8 vs. 3.8) and had more nonfatal diagnoses. Use of five or more different prescription drugs during 1994 was common (39.0%), and multivariate analysis showed that the greatest number of primary care visits occurred with multiple drug use (±5 drugs over 1 y).

This study shows an extensive multiple drug use among elderly people living at home. Whether this multiple drug use per se is harmful to the patients or not could not be evaluated in this study. Further focused investigations are needed to assess the effect of multiple drug use in an elderly population.

Hypertension is poorly controlled in the US due to medication nonadherence. Recent evidence suggests that nonadherence can be classified as intentional or unintentional and different patient characteristics, such as the experience of adverse effects, may be associated with each.

To examine associations between patient characteristics, including reported adverse effects, and both intentional and unintentional nonadherence among 588 hypertensive patients.

Baseline data from a clinical trial, the Veterans' Study To Improve the Control of Hypertension, were examined. Intentional and unintentional nonadherence were assessed using a self-report measure. Participants were presented with a list of adverse effects commonly associated with antihypertensive medication and asked to indicate which symptoms they had experienced. Logistic regression analyses were used to examine adjusted associations between patient characteristics and type of nonadherence.

Approximately 31% of patients reported unintentional nonadherence and 9% reported intentional nonadherence. Non-white participants, individuals without diabetes mellitus, and individuals reporting ≥5 adverse effects were more likely to report intentional nonadherence than their counterparts. Individuals with less than a 10th-grade education and non-white participants were more likely to report unintentional nonadherence than their counterparts. When symptoms of increased urination and wheezing/shortness of breath were reported, patients were more likely to report intentional and unintentional nonadherence compared with those who were adherent. Unintentional nonadherence was also associated with reports of dizziness and rapid pulse.

Both intentional and unintentional nonadherence are common and related to perceived adverse effects. Furthermore, different interventions may be necessary to improve adherence in unintentionally and intentionally nonadherent patients.

To review the literature concerning the history, development, and therapeutic uses of bisphosphonates.

English-language articles were identified through a search of MEDLINE (through December 2004) using the key word bisphosphonate. Reference lists of pivotal studies, reviews, and full prescribing information for the approved agents were also examined.

Selected studies included those that discussed the discovery and initial applications of bisphosphonates, as well as their historical development, pharmacokinetic and pharmacodynamic properties, and current therapeutic uses.

Bisphosphonates structurally resemble pyrophosphates (naturally occurring polyphosphates) and have demonstrated similar physicochemical effects to pyrophosphates. In addition, bisphosphonates reduce bone turnover and resist hydrolysis when administered orally. The information gained from initial work with etidronate generated a considerable scientific effort to design new and more effective bisphosphonates. The PCP moiety in the general bisphosphonate structure is essential for binding to hydroxyapatite and allows for a number of chemical variations by changing the 2 lateral side chains (designated R¹ and R²). The R¹ side chain determines binding affinity to hydroxyapatite, and the R² side chain determines antiresorptive potency. Accordingly, each bisphosphonate has its own characteristic profile of activity.

The bisphosphonates reduce bone turnover, increase bone mass, and decrease fracture risk and therefore have a significant place in the management of skeletal disorders including osteoporosis, Paget's disease, bone metastases, osteogenesis imperfecta, and heterotopic ossification.

To review and evaluate clinically relevant epidemiology, microbiology, and clinical studies regarding the treatment of multidrug-resistant Acinetobacter infections.

Pertinent literature was identified by a MEDLINE search (1966-September 2003) and through secondary bibliographies of pertinent articles.

All English-language articles identified from data sources were evaluated for clinical relevance.

Acinetobacter baumannii has emerged as a worldwide problem as a nosocomial pathogen in hospitalized patients. Acinetobacter spp. can cause a multitude of infections including pneumonia, bacteremia, meningitis, urinary tract infections, and skin and soft tissue infections, and the mortality associated with these infections is high. Isolates resistant to almost all commercially available antimicrobials have been identified, thus limiting treatment options. The development of new agents and reappraisal of older compounds (ie, polymyxins, ampicillin/sulbactam) are necessary as we consider the optimal treatment of these multidrug-resistant organisms.

There is no simple answer to the treatment of Acinetobacter infections. Eradication of Acinetobacter spp. requires adherence to good infection control practices and prudent antibiotic use, as well as effective antimicrobial therapy. Alternative therapies such as colistin, ampicillin/sulbactam, and tetracycline are potential options, but prospective, randomized, controlled trials are still lacking.

Non—cystic fibrosis (CF) patients with bronchiectasis usually develop chronic bronchial infection with Pseudomonas aeruginosa (PA) that is related to worsening lung function and increased morbidity and mortality.

To determine whether direct aerosol delivery of tobramycin to the lower airways may control infection and produce only low systemic toxicity.

A double-blind, placebo-controlled crossover trial involving 30 patients was conducted to determine the clinical effectiveness and safety of 6-month tobramycin inhalation therapy. Patients received 300 mg of aerosolized tobramycin or placebo twice daily in 2 cycles, each for 6 months, with a one-month washout period. The number of exacerbations, number of hospital admissions, number of hospital admission days, antibiotic use, pulmonary function, quality of life, tobramycin toxicity, density of PA in sputum, emergence of bacterial resistance, and emergence of other opportunistic bacteria were recorded.

The number of admissions and days of admission (mean ± SD) during the tobramycin period (0.15 ± 0.37 and 2.05 ± 5.03) were lower than those during the placebo period (0.75 ± 1.16 and 12.65 ± 21.8) (p < 0.047). A decrease in PA density in sputum was associated with tobramycin administration in the analysis of the first 6-month cycle (p = 0.038). No significant differences were observed in the number of exacerbations, antibiotic use, pulmonary function, and quality of life. The emergence of bacterial resistance and other bacteria did not differ between the 2 periods of study. Inhaled tobramycin was associated with bronchospasm in 3 patients, but not with detectable ototoxicity or nephrotoxicity.

Aerosol administration of high-dose tobramycin in non-CF bronchiectatic patients for endobronchial infection with PA appears to be safe and decreases the risk of hospitalization and PA density in sputum. Nevertheless, pulmonary function and quality of life are not improved, and the risk of bronchospasm is appreciable.

Multiple measures of adherence have been reported in the research literature and it is difficult to determine which is best, as each is nuanced. Occurrences of medication switching and polypharmacy or therapeutic duplication can substantially complicate adherence calculations when adherence to a therapeutic class is sought.

To contrast the Proportion of Days Covered (PDC) adherence metric with 2 variants of the Medication Possession Ratio (MPR, truncated MPR).

This study was a retrospective analysis of the North Carolina Medicaid administrative claims data from July 1999 to June 2000. Data for patients with schizophrenia (ICD-9-CM code 295.xx) who were not part of a health maintenance organization, not hospitalized, and not pregnant, taking at least one antipsychotic, were aggregated for each person into person-quarters. The numerator for PDC was defined as the number of days one or more antipsychotics was available and the MPR numerator was defined as the total days’ supply of antipsychotics; both were divided by the total days in each person-quarter. Adherence rates were estimated for subjects who used only one antipsychotic, switched medications, or had therapeutic duplication in the quarter.

The final sample consisted of 25,200 person-quarters from 7069 individuals. For person-quarters with single antipsychotic use, adherence to antipsychotics as a class was: PDC 0.607, truncated MPR 0.640, and MPR 0.695 (p < 0.001). For person-quarters with switching, the average MPR was 0.690, truncated MPR was 0.624, and PDC was 0.562 (p < 0.001). In the presence of therapeutic duplication, the PDC was 0.669, truncated MPR was 0.774, and MPR was 1.238 (p < 0.001).

The PDC provides a more conservative estimate of adherence than the MPR across all types of users; however, the differences between the 2 methods are more substantial for persons switching therapy and prescribed therapeutic duplication, where MPR may overstate true adherence. The PDC should be considered when a measure of adherence to a class of medications is sought, particularly in clinical situations in which multiple medications within a class are often used concurrently.