In recent years, drug delivery systems (DDS) have been developed, along with anticancer agents for those systems based on the concept of achieving a better clinical response and tolerability. Several clinical trials have shown that these drugs have better clinical effects in the treatment of many cancers, leading to their expanded indications. Liposomal doxorubicin is one DDS agent used to treat AIDS-related Kaposi’s sarcoma and ovarian cancer in Japan. In addition to those two indications, the Food and Drug Administration (FDA) approved this drug for the treatment of multiple myeloma in 2007. Another DDS agent approved in Japan is nanoparticle albumin-bound paclitaxel, which has been used in the treatment of breast cancer. Most recently, this drug has been approved for the treatment of non-small cell lung cancer in the U.S.A. Although these DDS agents appear to be less toxic than conventional drugs, DDS-specific side effects such as various skin reactions, hypersensitivity reaction, and peripheral neuropathy sometimes occur. Therefore, medical staff must understand DDS anticancer agents fully, including characteristic side effects, to achieve the desired clinical outcomes.

Efficacy of therapeutic drug monitoring (TDM) of vancomycin (VCM) was retrospectively investigated in 184 patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. The incidence of nephrotoxicity was compared between the patients who received TDM practice (TDM group, n=73) and did not (non-TDM group, n=111). Creatinine clearance (CLcr) values decreased significantly after the VCM therapy in the non-TDM group (p<0.05). The patients with MRSA bacteremia or pneumonia were classified into two groups according to peak concentrations of VCM: above 25 μg/ml (Group A: n=29) and below (Group B: n=24). Mean duration of VCM therapy (14.1 d) in Group A was significantly shorter than that (27.0 d) in Group B. Mean cumulative total VCM doses (13.3 g) in Group A was significantly less than that (25.0 g) in Group B. These results indicate that monitoring peak concentration is essential to obtain better clinical effects for VCM therapy, and that the peak concentration above 25 μg/ml is more effective.

In spite of current recommended safe handling procedures, the potential for the exposure of healthcare providers to hazardous drugs exists in the workplace. A reliance on biological safety cabinets to provide total protection against the exposure to hazardous drugs is insufficient. Preventing workplace contamination is the best strategy to minimize cytotoxic drug exposure in healthcare providers. This study was conducted to compare surface contamination and personnel exposure to cyclophosphamide before and after the implementation of a closed-system drug transfer device, PhaSeal, under the influence of cleaning according to the Japanese guidelines. Personnel exposure was evaluated by collecting 24 h urine samples from 4 pharmacists. Surface contamination was assessed by the wiping test. Four of 6 wipe samples collected before PhaSeal indicated a detectable level of cyclophosphamide. About 7 months after the initiation of PhaSeal, only one of 6 wipe samples indicated a detectable level of cyclophosphamide. Although all 4 employees who provided urine samples had positive results for the urinary excretion of cyclophosphamide before PhaSeal, these levels returned to minimal levels in 2 pharmacists after PhaSeal. In combination with the biological safety cabinet and cleaning according to the Japanese guidelines, PhaSeal further reduces surface contamination and healthcare providers exposure to cyclophosphamide to almost undetectable levels.

The accuracy, safety and feasibility of, the compounding robot APOTECAchemo were evaluated in the clinical practice of Japan. Accuracy and precision of robotic preparations by APOTECAchemo was evaluated in 20 preparations of fluorouracil (FU) and cyclophosphamide (CPA) infusions by four pharmacists. Environmental and product contaminations with FU and CPA were evaluated by wipe testing. Robotic performance was compared with manual preparation in a biological safety cabinet. The number of robotic products, total compounding time and total pre-reconstitution time of lyophilized drugs between January 1, 2014 to December 31, 2015 were investigated. Robotic preparation resulted more accurate and precise (mean absolute dose error and coefficient of variation were 0.83 and 1.04% for FU and 0.52 and 0.59% for CPA) than those of manual preparation (respective values were 1.20 and 1.46% for FU and 1.70 and 2.20% for CPA). Drug residue was not detected from any of the prepared infusion bags with the robotic preparation, whereas FU was detected in two of four analyzed infusion bags with manual preparation. Average total time to make single anticancer drug preparation (compounding plus reconstitution of lyophilized drugs) was 6.11 min in the second half of 2015. During the study period, the highest percentage of production covered by APOTECAchemo was 70.4% of the total inpatient pharmacy activity. Robotic preparation using APOTECAchemo should give substantial advantages in drug compounding for accuracy and safety and was able to be successfully worked in Mie university hospital.