Systemic antifungal drugs are widely used in the haematology/oncology setting and exhibit numerous potential drug interactions and adverse events in cancer patients. Our results highlight the challenges related to antifungal drugs and should valuably contribute to a safe and efficient application of this increasingly important class of drugs.

An international myeloma meeting entitled "Challenging the current approaches to multiple myeloma- and other cancer-related bone diseases: from bisphosphonates to targeted therapy" was held in Freiburg, Germany in July 2011 to discuss novel insights into and approaches to myeloma bone disease and other bone-seeking tumors. This review briefly summarizes the most prominent data of the meeting and current literature on our understanding of bone disease, the role of imaging techniques, operative interventions and systemic bone-seeking treatment, all of which should further improve our future therapeutic choices.

2568 Introduction: Invasive mycoses show high morbidity and mortality rates among immunocompromised patients (pts), and have multiplied the use and costs of systemic antifungal drugs (SAD). Especially pts with induction chemotherapy for acute leukemia and pts after allogeneic stem cell transplantation are at a high risk. This challenges physicians, as various drug-related aspects have to be considered. As side by side comparisons in unselected high-risk pts with different SAD are lacking, we prospectively analysed the frequency, clinical relevance and severity of SAD-related problems in consecutive pre- and acute leukemic pts, a 'typical', rather than highly-selected study cohort, in order to improve the efficacy and safety of SAD treatment. Methods: SAD-analysis was performed by daily participation on ward rounds, consultation of ward physicians and review of pts' medication charts and laboratory values. Pt characteristics, side effects (SE), in particular development of renal and hepatic toxicity, potential drug interactions (DI), treatment outcome and costs were assessed. SAD were given according to EORTC-adapted guidelines. Results: Currently, data from 100 consecutive pts have been obtained (AML n=71, ALL n=20, MDS n=9), these showing a median age of 59 years (range 19–75). For SAD use and their respective indications, see Table 1. The frequency of 1, 2 or 3–5 SAD regimens/pt was 56, 28 and 16, respectively, with SAD combination therapy rarely being applied (3%). Pts with relapsed leukemia (n=28) vs. with initial leukemia diagnosis (n=72) received more than one subsequent SAD in 64% vs. 36%, respectively. The importance of detailed DI analyses was stressed with a substantial median number of 22 concomitantly administered medications (range 1–50). We identified 47 potentially interacting combinations of SAD and concomitant drugs (Table 1). In total, 88% of pts receiving SAD were affected by at least one DI. SE leading to a change of SAD occurred in 13%, 10% and 6% of pts receiving lip. amphotericin B, voriconazole and posaconazole, respectively. Fluconazole, which was applied prophylactically and was low dosed in all cases, and caspofungin, showed very favourable safety profiles, necessitating no therapy adaptations. Determining renal function (RF) deterioration by comparing median eGFR values at SAD-initiation vs. after SAD-medication-end revealed a considerable eGFR decrease of 17% for lip. amphotericin B, whereas caspofungin and azole SAD had no major effects on RF. Pts with liver predamage were preferably treated with caspofungin (median baseline bilirubin level of 0.9 mg/dl compared to ≤ 0.7 mg/dl for all other agents), showing excellent tolerability. In 2009, SAD accounted for 20% of our department's inpt drug expenses, including chemotherapeutics. Median SAD costs per analysed hospital stay in our pt cohort were 2813€, with 64% of pts inducing costs higher than 1000€. According to the increased SAD use in pts with relapsed leukemia, costs in this cohort exceeded those of pts with initial diagnosis by 109% (4794€ vs. 2290€). As posaconazole is increasingly used for prophylaxis and treatment of fungal infections, we are currently obtaining serum posaconazole levels using our previously published HPLC method for quantification [Neubauer W. J Chromatogr B 2009] to ensure sufficient protection in these high-risk pts. Data on obtained serum levels will be presented at the meeting. Conclusion: This ongoing real-life analysis highlights the high number of aspects related to SAD-treatment in a high-risk pt cohort and the need for close monitoring of pts to avoid negative effects of DI and to reduce the rate of SE. By detecting and analyzing frequent DI, SE as well as pharmacoeconomic aspects, it suggests to valuably contribute to a safe, efficient and economically appropriate use of SAD. Disclosure: Metzke: MSD Merck Sharp & Dohme GmbH: Research Funding. Engelhardt:MSD Merck Sharp & Dohme GmbH: Research Funding.

4250 Introduction: Drug-drug interactions (DDI) may lead to adverse drug events and constitute a risk for patients and a major challenge for treating physicians. Especially cancer patients receive a considerable number of concomitant drugs for the treatment of the underlying disease, the side effects of cancer therapy and due to preexisting comorbidities. As more and more older and severely compromised patients are treated today, polypharmacy and its related problems are of growing importance. However, data on the frequency and nature of DDI in cancer patients during hospitalization are rare. Methods: To determine the prevalence and nature of potential DDI, we performed a detailed chart review of all hospitalized patients in our hematology and oncology department during two randomly appointed days. All medications administered on these very days were extracted from the electronically archived patients' medical charts. DDI were identified and rated for severity and level of evidence using two different electronic interaction databases, Micromedex 2.0 and Lexi-Interact. Only DDI of at least moderate severity (i.e. rated as moderate, major or contraindicated) were included in the analysis, and documented irrespective of their actual clinical consequences. At the time of analysis, no routinely performed DDI screening or electronic DDI alert system was in place in our department. Results: Medication profiles from 157 inpatients were analyzed. Patients' median age was 62 years (range: 25–94). Underlying diseases were leukemia (n=51), lymphoma (n=49), solid tumors (n=49) and non-malignant diseases (n=8). We evaluated a total of 1748 drug prescriptions with a median of 11 drugs per patient and day (range: 1–22). The median number of drugs was 9 in patients with solid tumors, 11 in patients with leukemia, and 12 in patients with lymphoma or non-malignant diseases. We found a total of 1153 drug interactions rated as of at least moderate severity by either Micromedex or Lexi-Interact, which corresponds to 734 DDI/100 patient days. The drug classes most frequently involved comprised antibiotics (23%), antifungals (21%), diuretics (20%), corticosteroids (17%), calcium channel blockers (11%), immunosuppressants (10%), benzodiazepines (9%) and opioid analgesics (8%). Antineoplastic drugs constituted 2.7% of all prescribed drugs, and were involved in 47 DDI (4%). The severity rating for all DDI was contraindicated, major and moderate in 2%, 24% and 74% of cases, respectively, according to the respective higher rating of both databases. The median number of DDI per patient was 5 (range: 0–31), and was highest for patients with leukemia with a median number of 7. 85% of patients experienced at least one DDI, and 26% of patients were exposed to ≥10 DDI on the evaluated day. The level of evidence of the 1153 DDI identified was excellent, good, fair and poor in 10%, 45%, 44% and 1% of cases, respectively. To identify the most clinically relevant DDI, we also determined the frequency and nature of those DDI which were rated as major severity or contraindicated by both databases. 61 DDI fulfilled these criteria and occurred in 33/157 patients (21%). The level of evidence of those 61 DDI was excellent, good and fair in 18%, 28% and 54% of cases, respectively. The most frequently detected potential clinical consequences of the 61 DDI rated as major or contraindicated by both databases were QT-prolongation with a variety of drug combinations (n=36), extrapyramidal reactions of different combinations including metoclopramide (n=5), and cyclosporine toxicity in combination with voriconazole (n=4). Conclusions: This retrospective DDI analysis revealed a high percentage of patients encountering DDI, including contraindicated drug combinations. Although some of these DDI are difficult to avoid or well manageable through close monitoring of the patients' clinical condition or laboratory results, there is a strong need for rising awareness of DDI to avoid patient harm. This is of particular relevance in the hematology and oncology setting, where numerous drugs are being applied, including cytotoxic agents. By identifying the most relevant DDI in this setting, these results allow targeted physician education and highlight the need to implement an electronic prescription system with DDI alerts in close cooperation with clinical pharmacists. Disclosures: No relevant conflicts of interest to declare.