-- Back to Table of ContentsStudy Objective. To evaluate the differential effect on coagulation and fibrinolysis parameters of combination therapy with glimepiride-metformin and with rosiglitazone-metformin beyond their effect on glucose metabolism in patients with type 2 diabetes and metabolic syndrome.
Design. Multicenter, double-blind, randomized, controlled trial.
Setting. Two university-affiliated medical centers in Italy.
Patients. Ninety-five patients with type 2 diabetes for at least 6 months without glycemic control by diet and oral hypoglycemic agents to their maximum tolerated dosage and who also had metabolic syndrome.
Intervention. All 95 patients received metformin 1500 mg/day. In a randomized manner, 47 patients received glimepiride 2 mg/day and 48 patients received rosiglitazone 4 mg/day.
Measurements and Main Results. Body mass index (BMI), glycemic control, and coagulation and fibrinolysis parameters were evaluated at 3, 6, 9, and 12 months of treatment. Compared with baseline values, significant decreases in BMI, fasting plasma glucose, postprandial plasma glucose, and hemoglobin A1c were observed at 12 months in both the glimepiride and rosiglitazone groups (p<0.05 and p<0.01, respectively). Decreases in fasting plasma insulin and postprandial plasma insulin were observed at 12 months (p<0.05 and p<0.01, respectively) compared with baseline values in the rosiglitazone group. Furthermore, improvement in the Homeostasis Model Assessment index was observed only at 9 and 12 months (p<0.05 and p<0.01, respectively) compared with baseline in the rosiglitazone group. Significant improvement in plasminogen activator inhibitor (PAI)-1 was present in the rosiglitazone group after 9 months (p<0.05), and significant PAI-1 improvement was observed in the glimepiride and rosiglitazone groups after 12 months (p<0.05 and p<0.01, respectively).
Conclusions. The rosiglitazone-metformin combination significantly improved the long-term control of all insulin resistance-related parameters compared with the glimepiride-metformin combination. However, both combinations were associated with a slight but statistically significant improvement in PAI-1 value, related to a similar reduction in insulin resistance.
Key Words: rosiglitazone-metformin, glimepiride-metformin, type 2 diabetes, metabolic syndrome, combination therapy, antithrombotic effects.
(Pharmacotherapy 2005;25(5):637-645)
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Study Objective. To compare the effects of different calcineurin inhibitors on sirolimus pharmacokinetics during long-term, staggered administration in kidney transplant recipients.
Design. Randomized, open-label, parallel-group trial.
Setting. A medical center and one of its teaching hospitals in Taiwan.
Patients. Twenty-two de novo kidney transplant recipients.
Intervention. Patients received cyclosporine microemulsion or tacrolimus capsules twice/day in combination with once-daily sirolimus solution and corticosteroids. Sirolimus was administered 6 hours after the morning dose of cyclosporine or tacrolimus. After receiving a 6-mg loading dose of sirolimus, participants received sirolimus 2 mg/day for at least 7 days. Neither the cyclosporine nor the tacrolimus dosage was adjusted for at least 3 days before and during blood sampling for pharmacokinetic profiling.
Measurements and Main Results. One patient dropped out because of trimethoprim-sulfamethoxazole-related hepatotoxicity. We observed no differences between the two patient groups in terms of their demographic data, renal and liver function, or dosage of sirolimus during the study. During multiple-dose administration, the area under the whole-blood concentration-time curve and the peak and trough concentrations of sirolimus in the cyclosporine group were, respectively, 1.46 (95% confidence interval [CI] 1.21-1.71), 1.42 (95% CI 1.08-1.76), and 1.42 (95% CI 1.09-1.76) times higher than those of the tacrolimus group, even though sirolimus was administered 6 hours after the other agents.
Conclusion. Sirolimus pharmacokinetics may change significantly when calcineurin inhibitors are switched, even with staggered administration, which may not completely prevent a drug interaction between cyclosporine and sirolimus solution.
Key Words: cyclosporine, drug interactions, kidney transplantation, pharmacokinetics, sirolimus, tacrolimus.
(Pharmacotherapy 2005;25(5):646-653)
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Study Objective. Metabolife 356, an ephedra-containing weight-loss product, substantially increases the corrected QT (QTc) interval. Metabolife Ephedra Free, a similar supplement, contains caffeine and extracts of green tea, garcinia cambogia, and yerba mate. Its electrocardiographic (ECG) effects are not known. Therefore, we sought to determine the effect of this supplement on the QTc interval.
Design. Randomized, double-blind, placebo-controlled, crossover study.
Setting. University of Connecticut, Storrs Campus.
Subjects. Twenty healthy volunteers.
Intervention. A single capsule containing half the normal recommended dose of Metabolife Ephedra Free or matching placebo was administered in crossover fashion, with a 7-day washout period between treatments.
Measurements and Main Results. Baseline and three postdose ECG measurements were obtained, and QTc intervals were measured over a 5-hour study period. No significant differences in the QTc interval or other ECG variables were observed between the Metabolife Ephedra Free and placebo groups.
Conclusion. At half the recommended single dose, Metabolife Ephedra Free does not affect the QTc interval or other ECG variables over 5 hours. Dose-response studies and studies of longer duration should be conducted.
Key Words: Garcinia cambogia, hydroxycitric acid, green tea extract, epigallocatechin-3-gallate, EGCG, Metabolife Ephedra Free, ECG, QTc interval.
(Pharmacotherapy 2005;25(5):654-659)
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Study Objective. To compare persistence, switching, and discontinuation rates among patients taking brand-name selective serotonin reuptake inhibitors (SSRIs).
Design. Retrospective cohort study.
Data Source. Protocare Sciences managed care database.
Patients. A total of 14,933 patients with depression, posttraumatic stress disorder, or social anxiety disorder whose prescriptions for brand-name SSRIs were filled from January 1, 1999-June 30, 2002.
Measurements and Main Results. A total of 5598 patients received sertraline, 4131 citalopram, and 5204 paroxetine. Adherence status was categorized as persistence, switching (from one SSRI to another SSRI), and discontinuation. Persistence was determined based on the number of days’ supply of the prescribed drug, with a minimum of 15 days to refill. Survival analyses using life-table survival curves and Cox proportional hazard models were conducted. Age, sex, and copayment were covariates in the Cox proportional models. Sensitivity analysis with a longer time to refill was performed to determine whether the results were sensitive to the algorithm for determining adherence. Compared with patients receiving sertraline and citalopram, those receiving paroxetine had lower rates of persistence (23.79% vs 25.96% for sertraline [p=0.0093] and 26.56% for citalopram [p=0.0022]) and higher rates of switching (3.55% vs 3.32% for sertraline [p=0.5076] and 2.78% for citalopram [p=0.0359]) and discontinuation (72.66% vs 70.72% for sertraline [p=0.0258] and 70.66% for citalopram [p= 0.0334]). Survival curves showed that persistence rates with sertraline and citalopram were significantly greater than with paroxetine (p<0.05, log-rank and Wilcoxon tests). Age was an independent predictor of persistence; male sex and copayment were not. The comparisons across SSRIs were robust in the sensitivity analysis that varied the time to refill allowed.
Conclusion. Differences in the persistence rates were noted among patients receiving three brand-name SSRIs, with patients receiving paroxetine having lower persistence than those receiving sertraline and citalopram. Observed differences in persistence across SSRIs were not sensitive to model specifications. Prescription of SSRIs that demonstrate better adherence would benefit both the patient and the health care system.
Key Words: depression, selective serotonin reuptake inhibitor, SSRI, persistence, switching, discontinuation.
(Pharmacotherapy 2005;25(5):660-667)
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Study Objective. To estimate the costs of hospitalization for neutropenia among chemotherapy-treated patients with newly diagnosed non-Hodgkin’s lymphoma and to assess baseline patient factors associated with these costs.
Design. Retrospective cohort study.
Data Source. Linked Surveillance, Epidemiology, and End Results Program-Healthcare Cost and Utilization Project databases for Iowa from 1993-1998.
Patients. Patients with newly diagnosed non-Hodgkin’s lymphoma who received all inpatient care at Iowa hospitals during their first course of chemotherapy.
Measurements and Main Results. Neutropenia-related hospitalization costs were estimated from discharge abstracts found within the earliest of the following: 6 months after the diagnosis month, the date of bone marrow transplantation, or date of death. We performed univariate tests of differences in neutropenia-related hospitalization costs in all patients in the sample, as well as tests for neutropenia-related hospitalization costs, length-of-stay, and cost/inpatient day for patients with at least one hospitalization for neutropenia. We modeled total inpatient charges over the period for patients with at least one neutropenia-related hospitalization (multiple regression). A total of 1636 patients with non-Hodgkin’s lymphoma had chemotherapy in Iowa and met inclusion criteria; of these, 316 had at least one hospitalization for neutropenia. The 316 patients had 418 stays. Patients with advanced stage (vs limited stage), previous anemia (vs no anemia), positive Charlson comorbidity score (vs score of 0), and diffuse large cell histology (vs follicular) had higher mean neutropenia-related hospitalization cost/patient with non-Hodgkin’s lymphoma (p<0.05). Among those with neutropenia-related hospitalizations, a longer length of stay was associated with nonfollicular histologies, previous anemia, and positive Charlson score (p<0.05).
Conclusion. When estimating expected payments for neutropenia-related hospitalization in patients with non-Hodgkin’s lymphoma, payers need to be aware of the distribution of clinical characteristics in these patients.
Key Words: Surveillance, Epidemiology, and End Results Program, SEER Program, Healthcare Cost and Utilization Project, HCUP, linked databases, non-Hodgkin’s lymphoma, neutropenia, hospitalization costs.
(Pharmacotherapy 2005;25(5):668-675)
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Study Objective. To develop and validate a diabetes mellitus-specific risk-adjustment tool -- the diabetes severity index (DSI) -- to assist in predicting health care costs and resources within populations of patients with diabetes.
Design. Retrospective analysis of clinical and resource use for patients with a diagnosis of diabetes mellitus. Model estimation was conducted with half the sample, and validation analysis was conducted with the other half.
Setting. Southern Arizona Veterans Affairs Health Care System.
Patients. Seven hundred thirty-four patients with diabetes (710 men, 24 women; mean age 66 yrs).
Measurements and Main Results. Clinical measures of diabetes severity (known as the DSI) were used to predict three health care resource outcomes: risk of hospitalization, and total and ambulatory health care costs. Validity of the DSI was assessed by comparing the DSI with the revised chronic disease score (CDS). The DSI weights ranged from -471.5-3081.2 for total health care costs, from -304.3-1582.1 for outpatient costs, and -0.19-0.93 for risk of hospitalization. The DSI explained 6-8% of the variance in total and ambulatory costs and performed significantly (p<0.05) better than demographics alone, but was similar to the CDS. When the DSI was used with the CDS, up to 8% of variability in costs and use were explained.
Conclusion. The DSI was developed to stratify veterans with diabetes according to diabetes severity and comorbidity. Since additional variance in medical care costs were explained by combining the DSI and CDS, the two indexes may explain different dimensions of a patient’s severity of diabetes. However, the utility of such an index based on clinical measures to predict short-term use may be limited due to low yet significant variability explained in the outcomes.
Key Words: risk adjustment, diabetes, health care resources, costs, predictive models, severity of illness.
(Pharmacotherapy 2005;25(5):676-684)
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Study Objective. To compare adverse events related to anticoagulation in patients assigned to a pharmacist-managed anticoagulation service versus those receiving usual care.
Design. Retrospective cohort analysis.
Setting. Three hundred-bed community hospital.
Patients. Four hundred twenty patients referred for anticoagulation management.
Measurements and Main Results. Primary outcomes were the number of adverse events requiring patient hospitalization and the number of patients experiencing such events. Secondary outcomes were the median length of hospital stay/admission and the total number of hospital days. The total numbers of adverse events requiring hospitalization were three for the pharmacist-managed group and 14 for the usual care group (p=0.0153). The number of patients experiencing an adverse event requiring hospitalization was also lower for the pharmacist-managed group than for the usual care group (3 vs 10, p=0.0962). The median length of hospital stay associated with each adverse event was not significantly different between the two groups; however, the total number of hospital days accrued was higher in the usual care group.
Conclusion. At 6 months after discontinuation of the pharmacist-managed anticoagulation service, the frequency of adverse events increased significantly, resulting in both an increased number of hospitalizations and an increased number of hospital days accrued. This coordinated anticoagulation program using a pharmacist reduced warfarin-related complications.
Key Words: anticoagulation, warfarin, pharmacist-managed care.
(Pharmacotherapy 2005;25(5):685-689)
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Study Objectives. To identify the types and frequencies of adverse events associated with community-based amphotericin B infusion therapy. A second objective was to validate the effectiveness of a monitoring system, based on guidelines from the Infectious Diseases Society of America (IDSA).
Design. Retrospective medical record review.
Setting. Outpatient clinic at a tertiary care center.
Patients. One hundred five patients who received amphotericin B therapy from a home care provider between January 1997 and July 2002.
Measurements and Main Results A total of 113 courses of amphotericin B formulations were administered: liposomal amphotericin B, 41 courses (36%), amphotericin B deoxycholate, 31 courses (27%), amphotericin B lipid complex, 31 courses (27%), and amphotericin B colloidal dispersion, 3 courses (3%); an additional 7 courses consisted of sequential therapy with two different formulations. Nephrotoxicity was associated with 46 (41%) courses, electrolyte abnormalities with 40 (35%) courses, venous access device complications with 12 (11%) courses, and infusion reactions with 13 (12%) courses. Nephrotoxicity occurred most frequently in adults aged 60 years or older, solid organ transplant recipients, and those receiving concomitant cyclosporine. Only two (12%) of 17 courses in children younger than 13 years were associated with nephrotoxicity. Thirteen of all 113 courses resulted in patients requiring hospital admission due to their adverse events. Monitoring of electrolyte, serum creatinine, and blood urea nitrogen levels 2 or 3 times/week was adequate for identifying these events.
Conclusion. Significant rates of adverse events occurred in patients who received community-based amphotericin B infusion therapy. A monitoring system based on IDSA guidelines was effective in facilitating the detection and management of these adverse events.
Key Words: amphotericin B, community-based therapy, adverse effects, nephrotoxicity, monitoring.
(Pharmacotherapy 2005;25(5):690-697)
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Antiretroviral agents, especially nucleoside reverse transcriptase inhibitors, require significant dosage adjustments in patients who have renal dysfunction and the human immunodeficiency virus (HIV). Some antiretroviral agents and fixed combination preparations are contraindicated in this population. In addition, many preferred antiretroviral regimens may be difficult to administer conveniently in patients with decreased creatinine clearance or in those receiving renal replacement therapies. Some highly active antiretroviral therapy regimens, however, can be used conveniently in patients with HIV and altered renal function.
Key Words: highly active antiretroviral therapy, HAART, human immuno-deficiency virus, HIV, renal dosage adjustments, renal insufficiency, renal failure.
(Pharmacotherapy 2005;25(5):698-708)
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Cinacalcet is the first calcimimetic drug approved by the United States Food and Drug Administration for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. A literature search, performed by using PubMed and MEDLINE from January 1997-June 2004, identified articles concerning the efficacy and safety of cinacalcet in this patient population. Currently, Vitamin D and its analogs are considered first-line therapy for secondary hyperparathyroidism. However, use of these agents is often accompanied by an increase in serum calcium and phosphorus concentrations, a problem that often limits their use. Cinacalcet’s mechanism of action decreases parathyroid hormone, calcium, and phosphorus levels, offering potential advantages over the other treatments for secondary hyperparathyroidism. Additional clinical trials are needed to evaluate the long-term safety and efficacy of the drug as a first-line agent.
Key Words: cinacalcet, secondary hyperparathyroidism, calcimimetic.
(Pharmacotherapy 2005;25(5):709-716)
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Gemifloxacin is a synthetic fluoroquinolone antimicrobial agent exhibiting potent activity against most gram-negative and gram-positive organisms, such as the important community-acquired respiratory pathogens Streptococcus pneumoniae (including multidrug-resistant S. pneumoniae), Haemophilus influenzae, and Moraxella catarrhalis. The agent’s mechanism of action involves dual targeting of two essential bacterial enzymes: DNA gyrase and topoisomerase IV. Gemifloxacin was approved by the Food and Drug Administration in April 2003 for treatment of community-acquired pneumonia and acute bacterial exacerbation of chronic bronchitis. The drug has an oral bioavailability of approximately 71%. Approximately 20-35% of gemifloxacin is excreted unchanged in the urine after 24 hours. The elimination half-life of gemifloxacin is 6-8 hours in patients with normal renal function, supporting once-daily dosing. The 24-hour free-drug area under the plasma concentration-time curve:minimum inhibitory concentration ratio (f AUC0-24:MIC) associated with efficacy, based on results from in vitro and animal models of infection, is approximately 30. With a mean fAUC0-24 of approximately 3 µg•hour/ml (35% of total AUC0-24 of 8.4) and a median S. pneumoniae MIC for 90% of tested strains of 0.03, a f AUC0-24:MIC ratio of 100 would be expected after standard dosing (320 mg once/day). In clinical studies involving both hospitalized and outpatient populations, gemifloxacin has been highly effective in the treatment of community-acquired pneumonia and acute exacerbation of chronic bronchitis. Clinical success rates ranged from 93.9-95.9% in patients with community-acquired pneumonia and 96.1-97.5% in those with acute exacerbation of chronic bronchitis. Gemifloxacin is well tolerated; the frequency of adverse events with this agent is low. Most adverse events are mild-to-moderate in severity, with diarrhea (< 4%), nausea and rash (< 3%), and headache (< 2%) most commonly reported. Drug interactions with gemifloxacin are not common, although absorption is greatly reduced when given with divalent and trivalent cation-containing compounds, such as antacids. Due to its potent activity against many common gram-positive and gram-negative respiratory pathogens, its proven clinical efficacy, and its favorable safety profile, gemifloxacin is a highly effective empiric treatment for community-acquired lower respiratory tract infections.
Key Words: gemifloxacin, fluoroquinolones, Streptococcus pneumoniae, lower respiratory tract infections, pharmacokinetics-pharmacodynamics, adverse events, drug interactions, community-acquired pneumonia.
(Pharmacotherapy 2005;25(5):717-740)
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Infection with the human immunodeficiency virus (HIV) continues to affect millions of people worldwide. Preventive measures have done little to slow the transmission of the virus. Discovery of an effective vaccine to prevent HIV could have a tremendous impact on this global pandemic. However, the complex interactions between HIV and the host immune system have limited the progress in vaccine development. Traditional vaccination strategies have shown little promise. Currently, subunit vaccines, DNA vaccines, recombinant vector vaccines, and prime-boost strategies are being evaluated in clinical trials. Although many breakthroughs have been made in HIV vaccine research, only three candidate HIV vaccines have been studied in phase III clinical trials. The current strategies being investigated in the development of preventive HIV vaccines are reviewed.
Key Words: human immunodeficiency virus, HIV, preventive vaccine, vaccine development, vaccine.
(Pharmacotherapy 2005;25(5):741-747)
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High-dose intravenous methotrexate is an important component of many effective chemotherapeutic regimens for childhood acute lymphoblastic leukemia (ALL). Its use has a strong pharmacologic rationale: to overcome mechanisms of resistance of the malignant cells and to achieve cytotoxic concentrations in sanctuary sites for lymphoblasts. Although therapeutic progress in ALL during the past 4 decades has been closely associated with more widespread use of intravenous methotrexate and in progressively larger doses, little data exist to clearly support the use of high-dose intravenous methotrexate over a regimen of prolonged administration of low-dose methotrexate. The implied superiority of intravenous methotrexate mainly stems from studies that used identical leucovorin rescue with low-dose methotrexate or from studies of upfront window therapy in untreated children with ALL in which single standard doses of oral methotrexate were compared with high-dose intravenous methotrexate with leucovorin rescue. The evidence favoring administration of intravenous methotrexate for children with ALL is critically reviewed. Despite its extensive use, high-dose intravenous methotrexate has not been proved conclusively to be more effective than less toxic, less labor intensive, and less costly methods of methotrexate administration.
Key Words: acute lymphoblastic leukemia, ALL, leucovorin, methotrexate.
(Pharmacotherapy 2005;25(5):748-755)
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Anabolic-androgenic steroids are synthetic derivatives of testosterone that some athletes have used to enhance muscle mass and improve their athletic performance. Ephedrine is a potent sympathomimetic agent that can lead to cardiomyopathy similar to that seen with catecholamine excess. Adverse cardiovascular events attributed to anabolic steroid and ephedra use, such as arrhythmias, myocardial infarction, cardiomyopathy, and sudden death, are rarely reported. Bodybuilders have used g-hydroxybutyrate, a potent secretagogue of growth hormone, to promote muscle development. Although dilated cardiomyopathy is a known complication of excess growth hormone levels, it has not been associated with use of g-hydroxybutyrate. A healthy 40-year-old man was admitted to our hospital for new-onset congestive heart failure and severe acute hepatitis that developed several months after he began using anabolic-androgenic steroids, ephedra, and g-hydroxybutyrate supplements. Analysis with an objective causality assessment scale revealed a probable adverse drug reaction between the patient’s use of anabolic steroids, ephedra, and g-hydroxybutyrate and the development of his cardiomyopathy and acute liver injury.
Key Words: anabolic steroids, dilated cardiomyopathy, liver injury, ephedra, g-hydroxybutyrate, GHB, liquid ecstasy, Ma Huang.
(Pharmacotherapy 2005;25(5):756-761)
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Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.
Key Words: lone atrial fibrillation, arrhythmia, creatine monohydrate, herbal products, dietary supplements.
(Pharmacotherapy 2005;25(5):762-764)
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A 71-year-old Caucasian man diagnosed with myelodysplastic syndrome developed interstitial and alveolar fibrosis after receiving a 7-day course of azacitidine therapy. The patient’s pulmonary function began to deteriorate immediately after the administration of his chemotherapy regimen. Other potential causes of pulmonary toxicity were ruled out such as viral, fungal, and bacterial pathogens, as well as other concomitant drugs. To our knowledge, this is the first case report documenting biopsy-proven interstitial and alveolar fibrosis associated with azacitidine. The frequency of this adverse drug reaction is unknown but may become more evident with increasing exposure of the population to azacitidine.
Key Words: azacitidine, interstitial fibrosis, alveolar fibrosis, myelodysplastic syndrome.
(Pharmacotherapy 2005;25(5):765-768)
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Two patients with chronic kidney disease experienced a major bleeding event, retroperitoneal hematoma, requiring a blood transfusion after the administration of enoxaparin. The first patient was a 61-year-old Caucasian woman with multiple comorbidities, including chronic kidney disease stage 4. She received subcutaneous enoxaparin 45 mg every 12 hours, along with antiplatelet agents. On the seventh day, she developed a large retroperitoneal hematoma and her hematocrit had decreased, requiring a transfusion of packed red blood cells. The second patient was a 74-year-old, obese Caucasian woman with multiple comorbidities, including chronic kidney disease stage 2-3 and atrial fibrillation. She was given enoxaparin 120 mg every 12 hours, along with warfarin and aspirin to prevent embolization. She developed a large retroperitoneal hematoma and died despite vigorous supportive care. Enoxaparin should be administered with great caution in patients with chronic kidney disease, especially if antiplatelet agents or other anticoagulants are administered concomitantly.
Key Words: anticoagulation, chronic kidney disease, enoxaparin, heparin, retroperitoneal hematoma.
(Pharmacotherapy 2005;25(5):769-772)
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A 47-year-old renal transplant recipient came to the transplant clinic with a serum creatinine level that was elevated above her baseline value. She had been taking celecoxib for arthritic pain. She was told to discontinue the drug, and shortly after, her serum creatinine level returned to baseline. Several case reports describe nephrotoxicity with cyclooxygenase (COX)-2 inhibitors. However, only two of these reports involved renal transplant recipients, and in both, rofecoxib was the COX-2 inhibitor of concern. To our knowledge, this is the first case report of a renal transplant recipient who developed nephrotoxicity while taking celecoxib. The potential renal effects of COX-2 inhibitors have received little attention, even though nonsteroidal anti-inflammatory drugs are considered to carry the risk of nephrotoxicity in patients with comorbidities such as diabetes mellitus and hypertension. Further studies are necessary to determine the safety of COX-2 inhibitors in transplant recipients and other patient groups that may be at heightened risk of nephrotoxicity.
Key Words: cyclooxygenase-2 inhibitors, celecoxib, nephrotoxicity, renal transplant, transplantation.
(Pharmacotherapy 2005;25(5):773-777)
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