Apixaban in patients with impaired renal function is supported by limited data. Landmark clinical trials evaluating apixaban in patients with atrial fibrillation and/or acute venous thromboembolism excluded patients with creatinine clearance (CrCl) <25 mL/min. This multicenter, retrospective chart review was conducted to evaluate the safety and effectiveness of apixaban compared with warfarin in patients with CrCl <25 mL/min. Included patients were newly initiated on apixaban or warfarin for at least 45 days with a CrCl <25 mL/min. Patients were evaluated for thrombosis and bleeding outcomes 6 months following initiation of anticoagulation. The primary outcome was the time to first bleeding or thrombosis event. A total of 128 patients met inclusion criteria in the apixaban group and 733 patients in the warfarin group. Time to first bleeding or thrombosis event was significantly different between the apixaban and warfarin groups. Cox proportional hazards model was conducted to control for potential confounding factors for the primary outcome. After controlling for atrial fibrillation and coronary artery bypass grafting, risk of thrombotic and bleeding events was lower in the apixaban group (hazard ratio, 0.47; 95% confidence interval, 0.25-0.92). There was not a statistical difference between time to thrombosis (83 days vs 54 days, P = .648), rate of thrombosis (5.5% vs 10.3%, P = .08), time to bleeding (46 days vs 54 days, P = .886), or rate of bleeding (5.5% vs 10.9%, P = .06). The severity of bleeding and thrombotic events was not different between groups. Apixaban may serve as a reasonable alternative compared with warfarin in patients with severe renal dysfunction.

Naltrexone/bupropion is an investigational combination for weight loss and maintenance in patients who are obese or have a BMI ≧ 27 kg/m² with comorbid diabetes, hypertension or hyperlipidemia. Pooled results from four phase 3 trials reveal placebo-subtracted mean weight loss of 4.7% (range 3.2–5.2%) with naltrexone/bupropion after 1 year (p < 0.001 vs. placebo in each trial). The placebo-subtracted proportion of patients achieving ≧5% weight loss with naltrexone/bupropion ranged from 26 to 33% (p < 0.001 vs. placebo in each trial). In the majority of phase 3 trials, naltrexone/bupropion significantly improved proportion of patients achieving ≧10% weight loss, waist circumference, triglycerides, high-density lipoprotein, fasting insulin, insulin resistance, and obesity-specific quality of life compared to placebo. In patients with diabetes, naltrexone/bupropion therapy decreased hemoglobin A1c (HbA1c) approximately 0.5% more than placebo (p < 0.001). Common side effects associated with naltrexone/bupropion include nausea, constipation, vomiting, dizziness, and dry mouth. Greater improvement in systolic blood pressure and pulse were seen with placebo compared to naltrexone/bupropion (p < 0.001). Further studies are necessary to determine the effect of naltrexone/bupropion on cardiovascular outcomes. The safety and efficacy of naltrexone/bupropion in weight management is reviewed in this article.

Riociguat is the first approved medication from the novel class of soluble guanylate cyclase (sGC) stimulators and the only agent approved for treating both chronic thromboembolic hypertension (CTEPH) and pulmonary arterial hypertension (PAH). The novel mechanism of riociguat lies in its ability to restore the homeostatic and therapeutic effects of nitric oxide that are diminished as a result of phenotypic alterations associated with pulmonary hypertension (PH). Improvements in 6-minute walk distance (6MWD) in patients with PAH during the phase 3 PATENT-1 trial were comparable to other oral agents approved for the treatment of PAH. Improvements in 6MWD in patients with CTEPH during the phase 3 CHEST-1 trial were greater than those previously observed with other oral PAH-directed therapies. Hypotension is the dose-limiting adverse effect of riociguat and dose titration is performed gradually according to systolic blood pressure. Riociguat was tolerated at maximal doses by most patients during PATENT-1 and CHEST-1 and was well tolerated during long-term extension studies. Key factors to consider with riociguat are a patient's systolic blood pressure, drug interactions mediated by CYP1A1, CYP3A4, and P-glycoprotein, cost, and teratogenicity requiring enrollment in a Risk Evaluation and Mitigation Strategy program. Recently published guidelines recommend riociguat monotherapy as an option for treatment-naïve patients with World Health Organization Functional Class (WHO FC) II or III symptoms or as add-on therapy for patients with persistent WHO FC III or IV symptoms being treated with an ERA or inhaled prostanoid. Postmarketing experience and ongoing clinical investigations will further define the safety and role of riociguat in patients with PAH and other types of PH.

A patient receiving daptomycin developed asymptomatic transaminitis and hyperbilirubinemia without concurrent multiorgan dysfunction or elevation of his creatinine kinase level. After ruling out other etiologies, the liver injury was attributed to daptomycin and was subsequently resolved. A single-center retrospective cohort analysis of baseline and follow-up liver function panels (n ‫؍‬ 614) from all admissions from 2008 to 2013 during which daptomycin was administered did not reveal any other cases of probable or definite drug-induced liver injury associated with daptomycin. Drug-induced liver injury (DILI) has been ascribed to Ͼ1,000 medications (1). While various scales have been developed to establish causality (e.g., the Naranjo probability scale, the Roussel Uclaf causality assessment method [RUCAM], the Maria and Victorino [M&V] scale, and the Council for International Organizations of Medical Sciences [CIOMS] scale), none has been adopted as a gold standard (2-5). The U.S. National Library of Medicine suggests that expert opinion is also suitable for attributing causality (see http://livertox.nih.gov/).Daptomycin has been associated with transaminase elevations in 3% of subjects (6) but not with other findings indicating a hepatic origin (e.g., gamma-glutamyl transferase [GGT]) (Cubist Pharmaceuticals Medical Affairs, written communication). Therefore, the elevations likely reflect myocyte injury, a known effect that necessitates creatinine kinase (CK) monitoring. One previous case of daptomycin-associated DILI mirrored this pattern, while another report described a patient with multiorgan failure (7,8). The case discussed below is unique because the patient developed isolated asymptomatic liver injury.Case report. A 31-year-old man with a history of psychiatric disorders, degenerative disc disease with chronic back pain, and intravenous drug abuse presented with suicidal ideation. He also reported a productive cough, left-sided inspiratory chest pain, abdominal pain, and back pain. He denied using ethanol or drugs except previously prescribed oxycodone (30 mg every 4 h as needed) and alprazolam (2 mg daily). The physical exam revealed an abscess involving the left antecubital fossa, into which the patient eventually admitted to injecting crushed morphine tablets. No jaundice or hepatosplenomegaly was identified. He was febrile to 39.3°C. His urine drug screen was positive for opiates and benzodiazepines. His liver function test (LFT) values were elevated, including a total bilirubin level of 2.1 mg/dl, an aspartate aminotransferase (AST) level of 95 IU/liter, an alanine aminotransferase (ALT) level of 95 IU/liter, and an alkaline phosphatase (ALP) level of 150 IU/liter (Fig. 1). After ruling out vertebral osteomyelitis with a gallium-67-tagged white cell scan, the abdominal pain was attributed to opioid withdrawal, and the patient was treated with dicyclomine and an opioid taper.On hospital day 3, the blood cultures started at admission grew Gram-positive cocci, and vancomycin was initiated. Treatment ...