SUMMARYWhat is known and objective: The presence of cirrhosis has a multifaceted impact on hepatic drug metabolism. An area of concern and uncertainty in the care of patients with cirrhosis is the safe use of both prescription and over-the-counter medications. Comment: Retrospective studies indicate a high incidence of adverse drug reactions (ADRs) among patients with cirrhosis related to use of certain medication classes including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and non-steroidal anti-inflammatory drugs. Conversely, use of appropriate medications, such as statins, may be decreased in this population due to fear of precipitating hepatotoxicity. What is new and conclusion: Pharmacotherapy in cirrhosis is an area of uncertainty and heterogeneity in clinical practice. Prescribing and dosing guidelines are needed to decrease the risk of serious ADRs in this high-risk patient population. WHAT IS KNOWN AND OBJECTIVELiver cirrhosis is associated with compromised liver function, including the ability to metabolize drugs. The presence of cirrhosis has a multifaceted impact on hepatic drug metabolism. Higher plasma drug concentrations may occur due to reduced drug clearance in the setting of impaired hepatic blood flow 1,2 and altered activity of metabolizing enzymes and membrane transporters.2-4 For drugs with high protein binding and low hepatic extraction, hypo-albuminemia increases the fraction of unbound drug and can therefore heighten potential toxicity. 1,3,[5][6][7] Pharmacotherapy in cirrhosis is further complicated by the prevalence of concomitant renal dysfunction and need for multiple medications to manage the complications of cirrhosis, including varices, ascites and bacterial peritonitis. Patients with cirrhosis have tenuous physiology and are susceptible to a variety of complications. An area of concern and uncertainty in the care of patients with cirrhosis is the safe use of prescription and over-the-counter medications.3,8 Although hepatotoxicity is a common concern, patients with cirrhosis are generally at greater risk of renal failure, gastrointestinal bleeding and hepatic encephalopathy precipitated by medications. Adverse drug reactions (ADRs) constitute a significant cause of morbidity and mortality in the United States.9,10 An ADR is defined by the World Health Organization as an effect secondary to medication use which is 'noxious and unintended, and which occurs at doses used in man for prophylaxis, diagnosis or therapy '. 11 This definition is largely applied to the appropriate use of medications. More recently, the literature has focused on adverse drug events (ADEs), a more comprehensive term which refers to any injury resulting from medication use.12 ADEs and ADRs have been the focus of significant public and regulatory attention, prompting studies and guidelines aimed at decreasing their incidence. 10,12,13 Interventions and guidelines have been published for high-risk populations, including the elderly 14,15 patients with chronic kidney disease, 16 ...
Introduction: Contemporary dosing strategies for rabbit anti-thymocyte globulin (rATG) in kidney transplantation aim to reduce cumulative exposure, minimizing long-term adverse events. The use of ideal body weight-based dosing has been trialed, however concern for increased rejection post-transplant exists due to lower doses of rATG. Research Questions: The primary aim of this study was to compare rejection rates between rATG dosing protocols using actual body weight and ideal body weight and secondarily to evaluate cost savings following protocol implementation. Design: This was a retrospective study surrounding implementation of an ideal body weight-based dosing protocol for rATG. We compared 75 kidney transplant recipients in whom rATG was dosed based on actual body weight (pre-protocol group) to 64 in whom dosing was based on ideal body weight (post-protocol group), following a nine-month washout. Results: The mean cumulative rATG dose in the pre-protocol group was 6.3 mg/kg of actual body weight. When ideal body weight was used in the post-protocol group, the mean dose was 4.5 mg/kg of actual body weight. The rejection rate was 18.7% pre-protocol and 23.4% postprotocol, which did not represent a statistically significant difference (p = 0.491). The actual annual cost savings after protocol implementation exceeded $162,000, approximately $2,500 per patient. Conclusion: Results suggest ideal body weight-based dosing of rATG may reduce exposure and cost, without significantly impacting the risk of rejection in kidney transplant recipients. More studies are needed to confirm these findings.
Bipolar disorder (BD) lifetime prevalence estimates are 1-2% [3]. Patients with BD have a higher prevalence of liver disease as compared with matched controls (21.5% vs. 3.5%, odds ratio 7.58,
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