American Pharmacists Association

About: American Pharmacists Association is a other organization based out in Washington D.C., District of Columbia, United States. It is known for research contribution in the topics: Pharmacist & Pharmacy. The organization has 2413 authors who have published 1969 publications receiving 30470 citations. The organization is also known as: APhA & American Pharmaceutical Association.

Propoxyphene and warfarin interaction.

Abstract: TOTHEEDITOR: The choice of an analgesic in patients receiving oral anticoagulant treatment is not straightforward. A number of compounds, including aspirin, are contraindicated because of the increased risk of hemorrhage. Acetaminophen alone and in combination with propoxyphene (acetaminophen 325 mg, propoxyphene 32.5 mg) are common alternatives. We report a patient in whom the combination increased the anticoagulant response to warfarin. A 53-year-old male with a seven-year history of multiple sclerosis was admitted with a suspected deep vein thrombosis of the right calf. Clinical examination confirmed this and heparin was administered by continuous infusion for three days. Warfarin 5-6 mg/d was substituted and the prothrombin time maintained between 28-44 seconds. The Quick prothrombin time test with the Manchester Comparative Reagent was used to monitor response. Drug therapy at this time was dantrolene, mianserin, cephalexin, cyclopenthiazide with potassium, and acetaminophen. On January 18, acetaminophen 325 mg with propoxyphene 32.5 mg (2 tabs qid) was substituted for acetaminophen in an attempt to provide adequate pain relief. The prothrombin time increased to 80 seconds three days later but returned to previous levels in two days after discontinuation of warfarin and acetaminophen with propoxyphene. Warfarin 6 mg/d was reintroduced gradually and the prothrombin time remained stablebetween 24-36 seconds (Figure I). It appears that acetaminophen with propoxyphene potentiated the therapeutic effect of warfarin in this patient. This has been reported previously by Orme et al. who described two patients who developed haematuria following concurrent administration of warfarin and the combination product.' Acetaminophen has been shown to have little effect on the prothrombin time in patients receiving warfarin,\" although a recent report suggests that acetaminophen may increase the prothrombin time in patients receiving coumarin anticoagulants. 3 However this has yet to be verified and the mechanism by which this occurs is unclear. An increase in prothrombin time in this patient occurred only after substitution of acetaminophen with the combination product and therefore appears to be associated with propoxyphene. Warfarin and propoxyphene are metabolized by the same hepatic microsomal enzyme system and it has been suggested that they compete for these enzymes, resulting in increased plasma concentrations of warfarin.' Propoxyphene has been shown to inhibit the metabolism of phenytoin and carbamazepine. When administered with carbamazepine, propoxyphene significantly increased carbamazepine plasma levels, which resulted in adverse effects in a number of patients.' The metabolism of phenytoin in vitro is reduced significantly by propoxyphene, and phenytoin intoxication has been reported in one patient who periodically received this compound.' It therefore seems likely that in this patient propoxyphene inhibited the metabolism of warfarin, resulting in increased plasma warfarin levels and a loss of anticoagulant control. This interaction does not occur in every

GERPAC Consensus Conference – Guidance on the Assignment of Microbiological Shelf-life for Hospital Pharmacy Aseptic Preparations

Abstract: Abstract All dosage forms prepared in hospital pharmacies should be labelled with an appropriate shelf-life. This shelf-life should be validated taking chemical, physical and microbiological data into consideration. This guidance focuses on parenteral aseptically prepared products, as they are high-risk preparations. The risk is exacerbated by a requirement for longer shelf lives for reasons of economy and efficiency. The scope of this guidance includes individual patient preparations, preparations prepared in series (same type of preparation being repeatedly prepared) and batch preparations prepared from the same initial bulk admixture.

Survey of cyclosporin‐sparing agent use in Australasian transplant centres

Abstract: Background: The coprescription of drugs which elevate cyclosporin blood concentration has been advocated to reduce the costs associated with use of this expensive immunosuppressive drug. This is the first time that drugs have been widely prescribed for an economic purpose and while it is thought to be widespread, there are little published data on the extent of this practice in Australia and New Zealand. Aims: To determine the extent to which cyclosporin sparing agents are used by Australian and New Zealand organ transplant centres, to determine which agents are used and why these agents are used by some but not all centres. Methods: Organ transplant centres were surveyed via a questionnaire. Results: Considerable variation in use of cyclosporin sparing agents exists both within and across organ transplant types by Australian and New Zealand transplant centres. Diltiazem use is more widespread than ketoconazole. Conclusions: Little of the variability in use of cyclosporin sparing agents can be explained by scientific considerations. While the central government benefits from the significant cost savings achieved by the use of cyclosporin sparing agents, individual transplant units may not. Transplant units may however be the major target in the event of litigation arising as a result of adverse effects. The availability of generic brands and improved formulations of cyclosporin may affect the viability of using cyclosporin sparing agents

An update on current and emerging therapies for epithelial ovarian cancer: Focus on poly(adenosine diphosphate-ribose) polymerase inhibition and antiangiogenesis.

Abstract: Epithelial ovarian cancer is the leading cause of death from gynecologic tumors in western countries. Newly diagnosed epithelial ovarian cancer patients usually have good initial response to combination of platinum-based and taxane-based chemotherapy. However, most patients eventually experience relapses, and responses to subsequent therapies are generally short-lived. Intraperitoneal chemotherapy has been shown to improve survival outcomes, but toxicities and logistics limit its acceptance. Dose-dense schedule of paclitaxel combined with carboplatin remains controversial, and more studies are needed to validate this approach. About 15% of epithelial ovarian cancer patients carry gene mutations in BRCA1 and/or BRCA2. The development of poly(adenosine diphosphate-ribose) polymerase inhibitors represents a novel therapeutic strategy, in which poly(adenosine diphosphate-ribose) inhibition leads to the formation of double-stranded DNA breaks that cannot be accurately repaired in BRCA1- or BRCA2-mutated tumors, thus leading to tumor cell death. This principle of synthetic lethality can be demonstrated by olaparib, an oral agent that inhibits the repair of single strand DNA breaks during DNA replication, causing defective homologous recombination and hence tumor cell death. Currently, many poly(adenosine diphosphate-ribose) inhibitors are in different phases of development. Furthermore, mechanisms of defective homologous recombination pathway may include other genetic and epigenetic abnormalities in addition to either germline or somatic BRCA1 and/or BRCA2 mutations, making these pathways as potential therapeutic targets. The clinical pharmacology, clinical efficacy, safety, administration issues of olaparib and current clinical development of poly(adenosine diphosphate-ribose) inhibitors are described in this article, along with an overview on the treatment options (including intraperitoneal chemotherapy and dose-dense chemotherapy) for epithelial ovarian cancer. On the other hand, overexpression of the vascular endothelial growth factor and increased angiogenesis are associated with the development and progression of epithelial ovarian cancer. Although there are some expected toxicities associated with antiangiogenesis, combination of bevacizumab and systemic chemotherapy improves the progression-free survival and response rate compared to chemotherapy alone. The clinical efficacy of adding bevacizumab and its safety for advanced epithelial ovarian cancer is also reviewed, with emerging data on antiangiogenesis therapy.