Background: Denosumab, a RANK-ligand inhibitor, is an effective treatment for osteoporosis in postmenopausal women and men. Unlike the bisphosphonates, it is not excreted by the kidney. Little is known, however, about its efficacy and safety in patients with severe chronic kidney disease (CKD). Methods: A retrospective study was performed in CKD 4-5D patients from a tertiary referral hospital who were treated with denosumab between 1st January 2011 and 31st March 2014. Data collected included information about the following: CKD stage, fracture history, bone mineral density, serum calcium levels pre and post denosumab treatment, episodes of hypocalcemia, relevant medications and adverse events. Results: Eight patients with CKD-5 and 6 patients with CKD-4 were identified (all female, mean age 77.1 ± 9.9). The mean pre-denosumab calcium value was 2.42 ± 0.12 mmol/l, PTH 20.2 ± 14.7 pmol/l and 25-OH vitamin D 69.1 ± 30.1 nmol/l. After denosumab treatment, 6/8 patients with CKD-5/5D, and 2/5 patients with CKD-4 developed severe hypocalcemia. Two patients developed direct adverse complications of hypocalcemia (seizure, laryngospasm, prolonged QT_c). Among the patients who developed hypocalcemia, the median time to serum calcium nadir was 21 days and the median time to correction of hypocalcemia was 71 days. Treatment of hypocalcemia required large doses of oral calcium and calcitriol, and increases in dialysate calcium concentration. Conclusions: A high rate of severe hypocalcemia was observed in patients with advanced CKD treated with denosumab. If denosumab is used in patients with severe CKD, close monitoring and aggressive replacement of calcium and calcitriol is required to avoid the development of hypocalcemia.

Abstract:Older people are at increased risk of medication-related problems and adverse medication events. This paper reviews literature on problems with medicine use in older Australians published between 2006 and 2013. The prevalence of polypharmacy has continued to rise. Polypharmacy, multiple comorbidities and inappropriate prescribing have been linked to drug-drug and drug-disease interactions and medicine-related hospitalisations. Inaccurate medication histories, suboptimal continuity of medication management, complex medication regimens and non-adherence have been reported. Studies describing medication reviews, usually conducted by pharmacists, indicate that older people taking multiple medicines have an average of one to three current medication-related problems, including inappropriate or unnecessary medicines, untreated indications, suboptimal monitoring and adverse drug reactions. These findings indicate that problems with medicine use and adverse medication events remain highly prevalent in older Australians, despite the introduction of a range of quality use of medicines strategies. This may be due to a range of factors such as increasing intensity and complexity of medical therapy, and suboptimal uptake and /or targeting of quality use of medicines strategies. In settings where quality use of medicines strategies have been implemented, there is evidence for improved prescribing and, in some situations, reduced adverse events. Problems with medicine use in older people remain a major challenge to the Australian healthcare system: polypharmacy may be unavoidable in people with multiple comorbidities, so there needs to be a focus on managing and reducing the risks associated with polypharmacy.

No abstract

Aim To determine clinical staff's understanding of managing oral medications in patients with restrictions on oral intake. Method An online survey was designed consisting of 4 scenarios featuring a patient who was fasting pre‐surgery, day 1 post‐surgery, nil‐by‐mouth after stroke or had a nasogastric feeding tube in situ. The target population was clinical staff (nursing, medical, pharmacy, dietetics, speech pathology) involved in the management of oral medications and/or patients' oral intake. Medications studied were: aspirin (Cartia) 100 mg mane; gliclazide (Diamicron MR) 60 mg mane; atorvastatin (Lipitor) 40 mg mane; metoprolol (Betaloc) 50 mg bd; levodopa/carbidopa (Sinemet CR) 200/50 tds; ginkgo 7500 complex mane. Respondents could choose to give, withhold, cease, contact someone for advice, change the formulation before giving or choose ‘other’ and make a comment. Results 622 responses were received from clinical staff. When fasting, respondents would give metoprolol (65%) and levodopa (68%) but not aspirin (70%), gliclazide (63%), atorvastatin (50%) and ginkgo (65%). Approximately 10% of respondents would give oral medications to the nil‐by‐mouth patient. The consensus for the nasogastric feeding tube was to give all the medications via the tube, including modified‐ or controlled‐release medications. Conclusion There appeared to be varying understanding of managing oral medications when patients have restrictions on oral intake. This is concerning as it has the potential to result in adverse patient outcomes.

Despite having well‐established clinical roles in many specialties, hospital pharmacists have not traditionally provided clinical services in the operating suite (OS). This paper describes the introduction of a clinical pharmacy service in the OS of a large metropolitan public hospital network. The initial focus of the service was on non‐clinical issues that were priorities for pharmacy and OS staff, such as medication supply, waste minimisation, expenditure, interdepartmental communication and legal compliance. Once ongoing funding for the positions was secured, cognitive clinical pharmacy services have become the focus. Benefits of the service have been demonstrated in medication safety, antibiotic stewardship and quality use of medicines. The 2 pharmacists have now become essential members of the OS. Work is underway to further develop pharmacists' roles in areas such as perioperative antimicrobial prescribing and perioperative management of patient's regular medication regimens to optimise the continuum of care.

Background: Metaraminol 10 mg/mL injection is often diluted with sodium chloride 0.9% and pre-drawn into syringes by anaesthetists for use in the management of intraoperative hypotensive crisis. The 10 mg/mL ampoule presentation poses a significant safety hazard since the entire content needs to be drawn into a syringe and then diluted so that 0.5 mg doses may be administered. There have been incidents where 10 mg rather than the intended 0.5 mg have been administered to the patient. Additionally the pre-drawn metaraminol is discarded at the end of the case if not used, which results in significant wastage. A pre-filled syringe presentation of metaraminol will improve patient safety and reduce wastage. Aim: To determine the feasibility and stability of metaraminol 3 mg/6 mL pre-filled syringes. Method: Metaraminol 10 mg/mL injections were diluted with sodium chloride 0.9% and repacked into 3 mg/6 mL syringes. Syringes were stored at three different conditions: room temperature, refrigerated and frozen. Metaraminol syringes from each storage condition were analysed in triplicate, using a validated high performance liquid chromatography assay on Days 0,1,7,14, 28, 58, 91, 126, 161, 189, 252, 315 and 378. A 5% change limit was used to assess stability. Results: Metaraminol 3 mg/6 mL syringes were stable when analysed up to Day 378 with levels remaining at 95.4 +/− 0.4% of initial concentration for both room temperature and refrigerated storage. In the frozen storage arm, samples that were defrosted immediately and 7 days prior to sampling exceeded the 5% limit by day 315 and day 378, respectively. Conclusion: Metaraminol 3 mg/6 mL pre-filled syringes are stable for up to 378 days when stored at room temperature, or refrigerated and this presentation is feasible for use in the operating theatre.

No abstract

A 59-year-old female underwent a renal transplant in early 2015. Her initial immunosuppression regimen was mycophenolate mofetil, prednisolone and tacrolimus. The post-transplant recovery was complicated by chronic diarrhoea. This was related to mycophenolate and occurred with both the mofetil and the sodium salts.In January 2016, while the patient was overseas, her diarrhoea worsened. She was admitted to hospital where mycophenolate sodium was stopped and azathioprine was started.When assessed back in Australia, one month after starting azathioprine, the patient was found to have severe pancytopenia and she was admitted to hospital. The azathioprine was stopped, but the pancytopenia persisted despite three weeks of treatment with filgrastim and blood products. It was complicated by febrile neutropenia and polymicrobial sepsis. The patient died one month after admission from multiorgan failure secondary to bone marrow failure. CommentAzathioprine, a prodrug of mercaptopurine, is a purine antimetabolite which suppresses the immune system. In addition to preventing the rejection of organ transplants, it can be used to manage a range of autoimmune and inflammatory conditions such as inflammatory bowel disease and systemic lupus erythematosus.The enzyme thiopurine methyltransferase (TPMT) is important for converting azathioprine and mercaptopurine into inactive metabolites. This reduces the consequent risk of myelosuppression. In 0.3-0.6% of Caucasians there are genetic polymorphisms that lead to markedly reduced TPMT activity.1 During her final admission our patient was found to have a genetic polymorphism, which resulted in low TPMT activity. This made her extremely sensitive to the myelosuppressive effects of azathioprine. The role of genetic testing is uncertain. Pathology laboratories often report intermediate-activity genetic polymorphisms, however the clinical implications of this result are unclear. TPMT activity can also be quantified by directly testing the enzyme's activity (often described as a TPMT phenotype). While this method should capture all patients with low TPMT activity, the result is subject to significant intraindividual variability. David Liew2 Either method of testing is practically effective in detecting patients with low enzyme activity. An alternative approach to the patient taking azathioprine is to frequently monitor the full blood count, looking for the onset of neutropenia. RecommendationsThis case highlights that low TPMT activity, although uncommon, can have fatal consequences, particularly if there are inadequate blood counts in patients taking azathioprine. Routine testing may be useful in predicting an individual patient's risk of myelosuppression, as well as adjusting dosing.3 It is easy to incorporate into standard practice, and is likely to have a favourable cost-benefit profile. 4 We recommend that TPMT testing should be strongly considered before starting azathioprine. Azathioprine use can usually be anticipated so testing should be done before the patient starts the drug.TP...