Hepatotoxicity associated with administration of voriconazole (VRCZ) is a major treatment-related adverse event and in some cases requires discontinuation of therapy. This study aimed to investigate the clinical course and risk factors for VRCZ-induced hepatotoxicity. Demographic and laboratory data were retrieved retrospectively from the medical records of 66 Japanese patients who underwent VRCZ treatment. VRCZ-induced hepatotoxicity was defined as an abnormal increase in liver function tests. VRCZ-induced hepatotoxicity was observed in 30 patients (45%), with 11 (37%) of these patients needing to discontinue the drug. Most of the events were observed within 1 to 2 weeks after the first dose of VRCZ. Of the liver function tests, an abnormal increase in γ-glutamyl transferase tended to occur earlier than changes in the other tests (ie, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin). Multiple logistic regression analysis showed that the trough concentration of VRCZ was a risk factor for hepatotoxicity (adjusted odds ratio = 2.89, 95%CI 1.49-5.59, P = 0.002). Based on this result, a VRCZ trough concentration < 4 μg/mL was considered to be the target for minimizing the risk of developing hepatotoxicity. After discontinuation of VRCZ in patients who developed hepatotoxicity, every liver enzyme abnormality improved within approximately 1 week. In conclusion, this study shows that VRCZ-induced hepatotoxicity may occur early after the initiation of VRCZ therapy. We therefore recommend appropriate adjustments of the starting dose and frequent liver function tests in patients treated with VRCZ, especially during the first 2 weeks.
The drug-induced lymphocyte stimulation test (DLST) and the cell migration analysis (CMA) are widely used as in vitro techniques to identify medicine causing drug-induced allergy (DIA). Unfortunately, however, the positive rate of these tests for identifying the causative drug in DIA is insufficiently high. In this study, we tried to establish a simple and rapid method with Jurkat cells and patients' serum to screen DIA before confirming by DLST and CMA. The sera were obtained from the healthy volunteer and the patients who had allergy-like symptoms and CMA. The real-time recording of cell mobility was performed up to 4 h using an optical accessible chmotaxis apparatus with Jurkat cells and patients' serum. When the kinetics of Jurkat cells were analyzed using the images of cell migration and the ImageJ software, the significant chemotaxis of Jurkat cells was observed against the sera of patients who had the drug for DIA identified by CMA. The positive rate of CMA rose from 16.7% to 50% after employing this rapid and beforehand method for diagnosing DIA followed by selecting patients' serum for the inspection. These results suggest that it may be an effective method for analyzing the kinetics of Jurkat cells with patients' serum before CMA for diagnosing the possibility of DIA.
Hand-foot skin reaction (HFSR) is one of the major adverse effects of sorafenib necessitating discontinuation of the drug, however, no standard interventions for HFSR have been established yet. At our hospital, we are using a urea-containing cream prophylactically for HFSR associated with sorafenib. We carried out this study in 74 hepatocellular carcinoma patients receiving treatment with sorafenib at our hospital between June 2009 and January 2011 to assess the benefit of prophylactic use of urea-containing cream against sorafenib-induced HFSR. Patients with a history of previous use of tyrosine kinase inhibitors or insufficient data in respect of the dose of urea-containing cream were excluded. The patients were divided into a high-dose group (38 patients) and a low-dose group (36 patients) according to the median dose (2.9 g per day) of urea-containing cream used within the first 2 weeks after the start of sorafenib treatment. The frequency of grade 2 or 3 HFSR was 42.1% in the high-dose group and 61.1% in the low-dose group(P = 0.105). The relative dose intensity of sorafenib was 71.1% in the high-dose group and 59.6% in the low-dose group (P = 0.043). No significant difference was observed in the response rate or time to progression between the two groups. In conclusion, prophylactic use of a urea-containing cream might enhance the relative dose intensity of sorafenib, but further prospective studies are warranted to elucidate its usefulness.
Mycoplasma pneumonia is caused by infection of Mycoplasma pneumoniae, and is a frequently occurring infectious disease transmitted from children to young adults. Macrolides are recommended as first-line drugs, minocycline (MINO) and tosufloxacin (TFLX) are used for the second-line drugs. In this study, we investigated the factors affecting the treatment period of mycoplasma pneumonia. We compared the effects of azithromycin (AZM), TFLX and MINO. The duration from hospitalization to defervescence was shorter in the MINO group than in the TFLX group. We then attempted to identify the factors that affect the treatment period of mycoplasma pneumonia. Patients who were treated in accordance with the Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2011 (Guideline) showed shorter duration of fever and disease duration as compared with patients who were not treated in accordance with the guidelines. In the case macrolides are ineffective, quickly switching to other drugs showed higher efficiency. In the light of these results, as treatment is carried out in accordance with the Guidelines, the disease and fever periods are shortened, and prolonged treatment in children could be prevented. These results also suggest that MINO is more effective for the treatment of mycoplasma pneumonia than TFLX.
Docetaxel plus cyclophosphamide (TC) therapy is standard adjuvant chemotherapy for breast cancer. In TC therapy, rash frequently occurs and results in decreased quality of life for patients. In this study, we performed a retrospective analysis of the efficacy of dexamethasone (Dex) for reducing rash associated with TC therapy. Forty-two patients treated with TC therapy at our hospital between April 2012 and March 2014 were examined. The patients were classified into a low Dex group (n = 17), who were administered Dex (6.6 mg) before chemotherapy, and a high Dex group (n = 25), who were administered Dex (13.2 mg) before chemotherapy. On Days 2-4, both groups were orally administered Dex (4 mg/day). The incidence of rash in the low Dex group was Grade 1: 29.4%, Grade 2: 41.2%, Grade 3: 11.8%; the incidence of rash in the high Dex group was Grade 1: 56.0%, and Grade 2: 16.0%. The incidence of rash in the high Dex group was significantly lower than that in the low Dex group (P = 0.031). In both groups, rash appeared frequently in the first course (no significant difference). No difference was observed considering other adverse events between the two groups. Additionally, no other adverse events caused by Dex were observed, including consumption of a sleeping pill, treatment for gastric ulcer, marked worsening of diabetes mellitus, or reactivated hepatitis B virus. Our investigation suggests that administration of increased Dex doses before chemotherapy with TC is effective in reducing rash.
Poor medication adherence contribues to insufficient blood pressure management among hypertensive patients. This is especially the case for elderly people who, despite having control over their medicine intake, fail to take their medicine. As a solution to the problem of medication adherence, a one-dose package medication support system was devised (patent pending). This system alerts users about the time for medication intake by a chime. Further, if a patient forgets to take his or her medicine over a preset period, a voice message is automatically transmitted to his or her medication supporter via telephone. The purpose of this study was to clarify how this system improves medication adherence among elderly hypertensive patients living at home. The participants were four elderly patients and eight medication supporters (two per elderly person). During the experimental period, June to September 2013, medication adherence was investigated using the system and home blood pressure measurement. Following the experimental period, the participants and medication supporters were interviewed. Medication adherence during the monitoring period was 100%. For one participant, the role of medication management shifted from the family to the patient. The results show that this system could eliminate instances of forgetting to take medicine or inappropriate intake of medicine. They also show that the one-dose package medication support system can give an accurate understanding of a patient's medication adherence.
In Japan, the online distribution of over-the-counter (OTC) drugs began in June 2014. A distributor has a duty to explain information about drugs to consumers, as well as to provide OTC drugs that have undergone quality control. In this study, we investigated the method of identifying health conditions of customers and the delivery channels of OTC drugs from the distributors to consumers, using 130 online stores as our sample. First-class OTC drugs were sold at 29 stores; pharmacists are required to explain information about these drugs to consumers. All the stores set up a column on which consumers could select their health conditions on a computer screen. However, in 25 of the stores, “no problem” had been inserted in the column beforehand. This meant that consumers could buy first-class OTC drugs without indicating their health conditions. Felbinac-containing poultices, which are contraindicated for pregnant women, were sold at 99 stores. However, consumers could buy the poultices at 91 stores without providing information about pregnancy. All the stores delivered OTC drugs through home delivery services, which did not store the drugs in cool conditions. In addition, some stores delivered suppositories by mail services in summer. These findings suggest the need for online distribution of OTC drugs to incorporate an improved method of providing drug information to consumers and ensuring quality control.
The emitted dose and mass median aerodynamic diameter of active ingredients from dry powder inhaler (DPI) are reported to be affected by the type of device, procedure and the inhalation flow rate of the patients. The purpose of this study was to clarify the effect of device shaking on the emitted dose of active ingredient from reservoir DPI by using Dosage Unite Sampling Apparatus (DUSA). A procaterol hydrochloride (PH)-containing DPI, Meptin® Clickhaler®, was used as a model DPI requiring shaking before use. After shaking by 7 test collaborators following the patient instructions, the amount of PH emitted into the DUSA using a vacuum pump was determined by high-performance liquid chromatography. Without device shaking, the emitted dose of PH was markedly low and varied widely, and the result suggested that device shaking was prerequisite for the efficient emission of active ingredient from DPI. The amount of PH emitted after shaking of the device varied largely between 7 test collaborators, while their averages were more than 80% of the labeled amount. In one collaborator, the ratio of emitted dose varied up to 30% among 4 experiences. Tapping the device before use also enabled the efficient emission of PH. Smaller particles were observed in Meptin® Clickhaler® compared to those in other reservoir DPIs that do not require shaking may explain the importance of shaking before use. These results confirmed the relevance of advice including the shaking methods by health-care personnel for appropriate use of the DPI formulations.