Brian J. Gates

Meloxicam: a reappraisal of pharmacokinetics, efficacy and safety

The discovery of two distinct isoenzymes of COX has led to the development and clinical introduction of COX-2 inhibitors with increased selectivity onto the market. Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class, and is a preferential inhibitor of COX-2, demonstrating effectiveness with anti-inflammatory, analgesic and antipyretic activity. Meloxicam is therapeutically utilised in the management of osteoarthritis and rheumatoid arthritis. Trials have examined the risk of gastrointestinal ulceration of meloxicam when compared with traditional non-specific COX-inhibiting NSAIDs with mixed results; meloxicam seems to have a greater gastrointestinal risk than the highly specific COX-2 NSAIDs. Meloxicam has a plasma half-life of ∼ 20 h and is convenient for once daily administration. Neither moderate renal nor hepatic insufficiency significantly alters the pharmacokinetics of meloxicam in short-term studies. Furthermore, dose adjustment is not required in the elderly. Recent drug–drug interaction studies have demonstrated that meloxicam interacts with some medications, including cholestyramine, lithium and some inhibitors of cytochrome P450 -2C9 and -3A4. Consequently, increased clinical vigilance should be maintained when coprescribing some medications with meloxicam. Concentration-dependent therapeutic and toxicological effects have yet to be extensively elucidated for meloxicam. Long-term safety in various organ systems, especially in the heart and vascular system and with concomitant drug administration, remains to be proven. The pharmacokinetics of meloxicam enables once daily application, which increases compliance compared with some shorter acting NSAIDs; however, long-term clinical data clearly demonstrating safety and efficacy advantages are lacking.

Review of osteoporosis pharmacotherapy for geriatric patients.

BACKGROUND Fractures are a significant problem in geriatric patients, and understanding the evidence for benefit and possible harm of osteoporosis treatments is critical to appropriate management of this patient population. OBJECTIVE The purpose of this article was to review the evidence and treatment considerations related to use of the approved osteoporosis treatments in the United States across the continuum of ages in the geriatric population. METHODS MEDLINE and the Web of Science were searched to find English-language articles published from 2000 through July 2009. Search terms included: practice guideline, osteoporosis, calcium, vitamin D, pharmacoeconomics, ethnicity, and treatment. The generic names of each of the osteoporosis treatments approved in the United States were searched to find relevant clinical trials and randomized controlled trials (RCTs). Pivotal trials that included fracture data or focused specifically on elderly patients (> or = 60 years of age) were selected. Bibliographies in the identified articles were searched for additional articles, and the prescribing information for each of the approved treatments was reviewed. RESULTS Many osteoporosis studies have a mean patient age >60 years, but data for older patients are limited. Subanalyses of older patient groups have found risedronate to be beneficial for vertebral fractures in patients aged 70 to 79 years (absolute risk reduction [ARR], 8.4%; P < 0.001) and teriparatide to be beneficial for both vertebral (ARR, 6.4%; P < 0.05) and new nonvertebral fragility fractures (ARR, 9.9%; P < 0.05) in women aged > or = 75 years. However, no RCTs of geriatric patients who were either nonambulatory or had multiple comorbidities were identified in the literature. CONCLUSIONS Evidence indicates that the osteoporosis treatments currently available in the United States are beneficial for treating osteoporosis in geriatric patients. However, data are limited for the oldest patients (> or = 80 years) and those with significant comorbidities. Because of the limited availability of data for geriatric patients with significant comorbidities, the properties of the various agents, including efficacy, tolerability, and potential contraindications, should be considered carefully for each geriatric patient.

Colesevelam Hydrochloride for the Treatment of Type 2 Diabetes Mellitus

BACKGROUND Colesevelam hydrochloride is a bile acid sequestrant approved in January 2008 by the US Food and Drug Administration (FDA) for the treatment of adult patients with type 2 diabetes mellitus (DM) in combination with a sulfonylurea, metformin, and/or insulin therapy. OBJECTIVE The purpose of this article was to review the pharmacology, pharmacokinetics, efficacy, adverse effects and tolerability, drug-drug interactions, contraindications/precautions, dosage and administration, pharmacoeconomics, and the overall role of colesevelam in the management of adult patients with type 2 DM. METHODS A literature search using MEDLINE (1966-October 27, 2008), PubMed (1950-October 27, 2008), Science Direct (1994-October 27, 2008), Web of Science (1980-October 27, 2008), American Diabetes Association Scientific Abstracts (2004-2008), and International Pharmaceutical Abstracts (1970-October 27, 2008) was performed using the term colesevelam. English-language, original research and review articles were examined, and citations from these articles were assessed. Manufacturer prescribing information and the FDA review of the new drug application for colesevelam were also examined. RESULTS Colesevelam is a hydrophilic, water-insoluble polymer, with negligible absorption and systemic distribution, that is excreted primarily in the feces. Through a mechanism still under investigation, colesevelam effectively lowers glycosylated hemoglobin (HbA(1c)) when used in combination with a sulfonylurea, metformin, and/or insulin therapy. Three completed, published Phase III clinical trials investigating colesevelam for the treatment of type 2 DM were evaluated for information, data, and conclusions. At dosing of 1.875 g BID or 3.75 g once daily in combination with one of the aforementioned agents versus placebo, reductions in HbA(1c) in all 3 Phase III clinical trials of colesevelam ranged from 0.5% to 0.7% (P < 0.02). In clinical trials, colesevelam was well tolerated, with hypoglycemia occurring in approximately 3% of studied patients. CONCLUSIONS When used in combination with a sulfonylurea, metformin, and/or insulin therapy, colesevelam has been reported to significantly reduce HbA(1c) in adult patients with type 2 DM. Colesevelams role in the management of type 2 DM remains undefined, however; further investigation into its mechanism of action and long-term efficacy and safety should be performed.

Management of osteoporosis in elderly men

Osteoporosis is a common condition associated with aging but has been considered to primarily affect women because of the substantial effect of menopause on osteoporosis. Bone density can decrease with aging in men but occurs more gradually than in postmenopausal women. With improvements in healthcare and extended life expectancy, it is becoming more apparent that osteoporosis affects men and can have serious consequences. Recently, a greater number of osteoporosis studies are either including men or focusing specifically on them. The majority of medication trials in men, however, used bone density as the primary outcome rather than fractures. Therefore, treatment data for men is still rather limited, and there is also very little information in the oldest subset of this population. The more recent guidelines for treating osteoporosis now include men, but the recommendations for screening and treatment are not necessarily gender specific. Despite the limited data, some osteoporosis treatments have received approval to treat or prevent osteoporosis specifically in men. Future studies must provide greater information on fracture prevention in men and also must include a greater population of the oldest geriatric patients, who are typically not well represented in osteoporosis trials, to evaluate any differences in both efficacy and side effects. The oldest group is important because they are at the highest risk for both osteoporosis-related complications and treatment-related adverse events.

Medication Intervention for Chronic Kidney Disease Patients Transitioning from Hospital to Home: Study Design and Baseline Characteristics.

Background: The hospital readmission rate in the population with chronic kidney disease (CKD) is high and strategies to reduce this risk are urgently needed. Methods: The CKD-Medication Intervention Trial (CKD-MIT; www.clinicaltrials.gov; NCTO1459770) is a single-blind (investigators), randomized, clinical trial conducted at Providence Health Care in Spokane, Washington. Study participants are hospitalized patients with CKD stages 3-5 (not treated with kidney replacement therapy) and acute illness. The study intervention is a pharmacist-led, home-based, medication management intervention delivered within 7 days after hospital discharge. The primary outcome is a composite of hospital readmissions and visits to emergency departments and urgent care centers for 90 days following hospital discharge. Secondary outcomes are achievements of guideline-based targets for CKD risk factors and complications. Results: Enrollment began in February 2012 and ended in May 2015. At baseline, the age of participants was 69 ± 11 years (mean ± SD), 50% (77 of 155) were women, 83% (117 of 141) had hypertension and 56% (79 of 141) had diabetes. At baseline, the estimated glomerular filtration rate was 41 ± 14 ml/min/1.73 m2 and urine albumin-to-creatinine ratio was 43 mg/g (interquartile range 8-528 mg/g). The most frequent diagnosis category for the index hospital admission was cardiovascular diseases at 34% (53 of 155), but the most common single diagnosis for admission was community-acquired acute kidney injury at 10% (16 of 155). Conclusion: Participants in CKD-MIT are typical of acutely ill hospitalized patients with CKD. A medication management intervention after hospital discharge is under study to reduce post-hospitalization acute care utilization and to improve CKD management.

A survey of the perceptions, knowledge, and use of A1C values by home care patients and nurses.

PURPOSE The purpose of this study was to provide baseline information on the perceptions, use, and knowledge of hemoglobin A1C (A1C) values among home healthcare nurses and patients. METHODS A convenience sample (44 patients, 26 nurses) from a Medicare-certified home care agency was surveyed using an investigator-developed demographic and knowledge questionnaire. Data collected from telephone interviews (patients), written questionnaires (nurses), and medicA1 record reviews were analyzed using descriptive methods. RESULTS Most of the home care nurses correctly identified the American Diabetes Associations recommendation for target A1C values; however, nurses rarely contact the physician to obtain A1C results. Nurses do not routinely teach patients about A1C values and inconsistently use A1C values to plan care for their patients with diabetes. Most patients said that they had never had an A1C test performed, and most did not recall the nurse providing any teaching about A1C. CONCLUSIONS Education related to target A1C values is needed. Methods to increase the availability of A1C results in the home care setting should be explored. The importance and clinicA1 utility of A1C values need to be more effectively conveyed to both nurses and patients in the home care setting.

A Comparison of Educational Methods to Improve NSAID Knowledge and Use of a Medication List in an Elderly Population

The objective of this study is to compare the effectiveness of pharmacist-provided individualized education with standardized video education for(a) improving patient understanding of gastropathy caused by nonsteroidal anti-inflammatory drugs (NSAIDs) and (b) stimulating the use of a medication list. Home care patients were assessed and then randomized to receive either video education or a tailored intervention from a home care pharmacist. Patients in the tailored group were more likely to keep an updated list (p = .033) and utilize it before purchasing over-the-counter medications (p = .043). Tailored education may be more effective than standardized video education for changing behaviors related to NSAID-induced gastropathy.

Risedronate’s Role in Reducing Hip Fracture in Postmenopausal Women with Established Osteoporosis

Osteoporosis is a significant concern for postmenopausal women and is a critical factor in hip fracture. Examining evidence for osteoporosis medications in hip fracture is important for optimizing treatment. Purpose Review risedronates role for hip fracture in postmenopausal women. Methods A literature search was conducted using Medline and Web of Science. The search was limited using the terms “risedronate” and “hip fracture,” and to studies that included women. Similar articles linked to the search and pertinent articles in bibliographies were also examined. Results Risedronate has demonstrated efficacy and cost effectiveness for hip fracture, but may not be beneficial for patients with low fracture risk. Risedronate is generally well tolerated, but may cause side effects in some patient populations. Conclusion Risedronate has benefit for hip fracture, but patients should be carefully screened to determine the appropriateness of risedronate before starting treatment.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Research to Help Your Patients Use them Safely

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective medications for the treatment of many chronically painful medical conditions. However, it is estimated that 25% of all serious adverse drug reactions involve NSAIDs, with more than 100,000 hospitalizations and 16,000 deaths occurring annually due to NSAID-induced gastrointestinal (GI) events. Advanced age; concurrent anticoagulant, aspirin, corticosteroid, or antacid use; and a history of cardiovascular disease, peptic ulcer disease, or GI hemorrhage all increase the risk of NSAID-induced gastropathy. Home care patients often have many of these characteristics. This article will provide evidence-based information about interventions that can reduce patients’ NSAID-induced gastropathy risk, including knowledge gained from a home care–specific study.