Real-life drug-drug and herb-drug interactions in outpatients taking oral anticancer drugs: comparison with databases.

PURPOSE: Due to polypharmacy and the rising popularity of complementary and alternative medicines (CAM), oncology patients are particularly at risk of drug-drug interactions (DDI) or herb-drug interactions (HDI). The aims of this study were to assess DDI and HDI in outpatients taking oral anticancer drug. METHOD: All prescribed and non-prescribed medications, including CAM, were prospectively collected by hospital pharmacists during a structured interview with the patient. DDI and HDI were analyzed using four interaction software programs: Thériaque®, Drugs.com®, Hédrine, and Memorial Sloan Kettering Cancer Center (MSKCC) database. All detected interactions were characterized by severity, risk and action mechanism. The need for pharmaceutical intervention to modify drug use was determined on a case-by-case basis. RESULTS: 294 patients were included, with a mean age of 67 years [55-79]. The median number of chronic drugs per patient was 8 [1-29] and 55% of patients used at least one CAM. At least 1 interaction was found for 267 patients (90.8%): 263 (89.4%) with DDI, 68 (23.1%) with HDI, and 64 (21.7%) with both DDI and HDI. Only 13% of the DDI were found in Thériaque® and Drugs.com® databases, and 125 (2.5%) were reported with similar level of risk on both databases. 104 HDI were identified with only 9.5% of the interactions found in both databases. 103 pharmaceutical interventions were performed, involving 61 patients (20.7%). CONCLUSION: Potentially clinically relevant drug interaction were frequently identified in this study, showing that several databases and structured screening are required to detect more interactions and optimize medication safety.

Comparative toxicities of 3 platinum-containing chemotherapy regimens in relapsed/refractory lymphoma patients.

Optimal salvage chemotherapy regimen for patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma remains unclear but often based on platinum regimens. This retrospective study assesses in real life the toxicities profiles of patients with relapsed or refractory lymphoma treated with DHA (dexamethasone, high dose aracytine cytarabine) plus platinum salt (dexamethasone-High dose aracytine (cis)platin (DHAP), dexamethasone-High dose aracytine carboplatin (DHAC), or dexamethasone-High dose aracytine Oxaliplatin (DHAOX)), from February 2007 to May 2013 in 2 French hospitals. Toxicities were recorded from medical files and assessed according to the National Cancer Institute Common Toxicity Criteria version 3.0. Potential risk factors of renal insufficiency were tested by univariate analyses. A total of 276 patients were treated: 168 with DHAP (60.9%), 79 with DHAOX (28.6%), and 29 with DHAC (10.5%). Rituximab was associated in 80.1% of patients (n = 221). Renal failure was reported in 97 patients, mainly with cisplatin regimen (86.6%) leading to 8.9% grade III to IV renal failure (P = .001). Renal insufficiency was reversible in most patients but remained persistent in 24, with all of them being treated with DHAP except 1. Cisplatin-based regimen (50.0% versus 12.0%, P < .05) and female (44.6% versus 29.7%, P < .05) appeared to be at higher risks of renal failure. Platinum cumulative dose is a significant risk factor of nephrotoxicity. Hematologic toxicity was more frequent with carboplatin and cisplatin with at least 1 event (all toxicity grade) respectively in 79.3% and 71.4% of patients treated (P < .005). Auditory toxicity was mainly reported with cisplatin (n = 19; 4 grade I-II and 15 grade III-IV). Oxaliplatin was implicated in 77.6% of neurotoxicity (n = 59), mainly moderate (grade I-II). In conclusion, DHAOX and DHAC regimens have more favorable toxicity profile than DHAP regimen. Their lack of renal toxicity makes them attractive regimens, which may be interesting for patients eligible for autologous stem cell transplantation. Nevertheless, these results have to be confirmed by the therapeutic efficacy of these 3 regimens.

New treatments for cutaneous metastatic melanoma: MAPK pathway-targeted and immune based therapies.

Increasing knowledge on cellular biology has permitted rapid changes in the treatment of metastatic melanoma. Until 2011, dacarbazine was the gold standard treatment at our disposal. In 2011 the treatment landscape changed dramatically with the approval by the FDA of ipilimumab and vemurafenib. These drugs use two new therapeutic approaches: immunomodulation and the targeting of mutated cellular pathways in tumor cells. These two drugs, used as single agents have shown important increases in overall survival, unseen before in patients with advanced melanoma, but are limited by their toxicities and the appearance of acquired resistances. In this article, we review new therapeutic options in pathway-targeted -with the arrival of MEK inhibitors - and immune based melanoma therapies -with the arrival of anti-PD1 and anti-PDL1- as well as new therapeutic strategies developed to overcome acquired resistance and diminish drug toxicities.

EPICC study: evaluation of pharmaceutical intervention in cancer care.

WHAT IS KNOWN AND OBJECTIVES: In cancer care, clinical pharmacists contribute to improving prevention and management of drug-related problems (DRPs). The 3-year EPICC study (Evaluation of Pharmaceutical Intervention in Cancer Care) aimed to collect and analyse pharmaceutical interventions (PIs) in oncology. METHODS: The free online version of the French Society of Clinical Pharmacy (SFPC) coding system, ACT-IP, was used, supplemented by a standardized dedicated cancer-care decision tree. RESULTS: A total of 29,589 medication orders (77,004 anticancer drug preparations) were analysed. Eight hundred and ninety-four PIs were recorded. ACT-IP identified 54·1% of DRPs as concerning over- or underdosage. The standardized dedicated cancer-care decision tree identified the three principal causes of dosage problems: 50·2% due to miscalculation, 20% to omission of dose adjustment and 12% to poor choice of antineoplastic regimen. About 13·8% of DRPs were adverse effects and 3·9% were drug-drug interactions. The decision tree showed that 22% of adverse events could be circumvented by a switch within the same drug family and 72% of drug-drug interactions would have led to increased neoplastic toxicity. DISCUSSION: Pharmaceutical analysis of prescription forms contributes to medication safety in cancer care, and the present dedicated decision tree highlights additional information about DRPs and PIs. The DRP rate (3% of prescriptions) was consistent with the literature. The pharmacist has a role to play in optimizing the management of patients with cancer in terms of dose adjustment, drug toxicity management, improvement of administration and drug-drug interactions. WHAT IS NEW AND CONCLUSION: This study, highlighting PIs in cancer care, is the first of this scale in terms of number of prescriptions analysed (nearly 30 000). Results demonstrated the specificity of DRPs and PIs for patients with cancer and the value of a dedicated coding system in cancer care.

SIMMEON-Prep study: SIMulation of Medication Errors in ONcology: prevention of antineoplastic preparation errors.

WHAT IS KNOWN AND OBJECTIVE: Medication errors (ME) in oncology are known to cause serious iatrogenic complications. However, MEs still occur at each step in the anticancer chemotherapy process, particularly when injections are prepared in the hospital pharmacy. This study assessed whether a ME simulation program would help prevent ME-associated iatrogenic complications. METHODS: The 5-month prospective study, consisting of three phases, was undertaken in the centralized pharmaceutical unit of a university hospital of Lyon, France. During the first simulation phase, 25 instruction sheets each containing one simulated error were inserted among various instruction sheets issued to blinded technicians. The second phase consisted of activity aimed at raising pharmacy technicians' awareness of risk of medication errors associated with antineoplastic drugs. The third phase consisted of re-enacting the error simulation process 3 months after the awareness campaign. The rate and severity of undetected medication errors were measured during the two simulation (first and third) phases. The potential seriousness of the ME was assessed using the NCC MERP(®) index. RESULTS AND DISCUSSION: The rate of undetected medication errors decreased from 12 in the first simulation phase (48%) to five in the second simulation phase (20%, P = 0.04). The number of potential deaths due to administration of a faulty preparation decreased from three to zero. Awareness of iatrogenic risk through error simulation allowed pharmacy technicians to improve their ability to identify errors. WHAT IS NEW AND CONCLUSION: This study is the first demonstration of the successful application of a simulation-based learning tool for reducing errors in the preparation of injectable anticancer drugs. Such a program should form part of the continuous quality improvement of risk management strategies for cancer patients.

Suspicion of drug-drug interaction between high-dose methotrexate and proton pump inhibitors: a case report - should the practice be changed?

We report a case of a potential drug-drug interaction in a woman treated by a first injection of high-dose methotrexate for a T-lymphoblastic lymphoma. Valaciclovir, fluoxetine and pantoprazole were given concomitantly. A methotrexate overdosage was shown at 36 h after infusion associated with a severe renal failure. Alkaline hyperhydration, folinic acid and carboxypeptidase G2 were given. Prescription analyses by pharmacists and literature research have permitted us to suggest that a drug-drug interaction between methotrexate and proton pump inhibitors (PPI) was responsible for this renal failure. Several mechanisms of interaction were suggested and might be related to the inhibition of renal methotrexate transporters by PPI, an increase in the methotrexate efflux to the blood by an upregulation of multidrug resistance protein 3 by PPI or genetic polymorphisms. This case shows that pharmacists can help physicians to optimize patient treatment: they consensually decided on the systematic discontinuation of PPI or a switch to ranitidine when patients were treated by high-dose methotrexate.