[Effectiveness of Allergy Regimen for Allergic Reactions to Oxaliplatin].

Oxaliplatin, a platinum-containing antineoplastic agent, is a key drug for the treatment of colorectal cancer and gastric cancer; however, some patients develop allergic reactions. Our hospital uses a regimen to control allergic reactions in patients with mild allergies(Grade 1 and 2). The aim of this study was to determine the effectiveness and safety of our allergy regimen. We retrospectively investigated 22 patients who initiated our allergy regimen between January 2017 and December 2017. The median number of administration cycles before allergy development was 8, and the median cumulative dose of oxaliplatin was 700mg/m2. Of the 22 patients, 18(82%)were able to continue oxaliplatin therapy. Drowsiness was the only adverse event that occurred in this cohort. Our allergy regimen may be effective for controlling allergic reactions to oxaliplatin in patients with mild allergies.

The effectiveness of rebamipide mouthwash therapy for radiotherapy and chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis.

BACKGROUND: Oral mucositis is a frequent and severe adverse event in patients undergoing chemoradiotherapy for head and neck cancers, especially grade 3 or 4 mucositis. Occurrence may result in drop-out from treatment, thereby reducing survival. We aimed to clarify the effectiveness and safety of rebamipide mouthwash for oral mucositis in patients with head and neck cancer receiving treatment. METHODS: We carried out a systematic review and meta-analysis of patients with head and neck cancer who were treated with rebamipide mouthwash. We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), and the World Health Organization (WHO) International Clinical Trial Registry Platform. The primary outcome was the incidence of severe oral mucositis, and secondary outcomes were time from treatment start to onset of oral mucositis, the response rate of radiotherapy, and any adverse events. RESULTS: We included three studies comparing rebamipide versus placebo, all of which evaluating chemoradiotherapy induced oral mucositis. The chemotherapeutic agent was docetaxel in one study and cisplatin in the remaining two. Radiotherapy in each study consisted of 3D-conformal radiation therapy, intensity modulated radiation therapy and conventional radiation therapy, respectively. The calculated odds ratio was 0.29 [95% confidence interval (CI): 0.15 to 0.55], showing a positive association in the three studies between the incidence of grade 3-4 oral mucositis and chemotherapy for head and neck cancer. One study reported an onset of oral mucositis and the time to onset was 14.6 ± 6.4 days for the rebamipide group and 11.2 ± 4.4 days for placebo. One study reported a complete response of 8.3% for placebo and 16.7% for the rebamipide the group, and the partial response was 91.7 and 75.0%, respectively. Adverse events were reported in two studies to be 6.1 and 11.6% for placebo, and 19.4 and 26.0% in the rebamipide group, respectively. CONCLUSIONS: Rebamipide mouthwash is effective in the prevention of severe mucositis and stomatitis. However, evaluation of adverse events in observational studies are needed.

[Applications of Raman Spectroscopy on Quality Control of Hospital Formulations].

Hospital formulation has several advantages, including the flexibility of customization as per the disease state or the patients' precise requirements. However, compared with commercial formulations, hospital formulations are usually not under the same level of quality check. In the present study, we tested mixed powder formulations prepared in a hospital pharmacy using Raman spectroscopy to investigate the feasibility of applying Raman spectroscopy as a quality-control tool of hospital formulations. For this purpose, we first established a numerical evaluation method to determine the uniformity of a powder mixture using Raman chemical imaging data with atropine sulfate/lactose mixture samples and revealed that the mixing uniformity correlated to the experience level of the pharmacist. Next, we developed a content quantification method in a one-dose packaged powder formulation by measuring the Raman spectra from the outside of the package. Because this method allows for quantification of the components inside the package in a non-destructive and non-contact manner, it can be applied for content confirmation after one-dose packaging. Using this method, the content uniformity of the mixed powder formulation in the one-dose package was compared between the formulations prepared by the pharmacists and those prepared by a pharmacy robot. Our study indicates the possibility of applying Raman spectroscopy as a quality-control tool of hospital formulations. Studies on further applications of Raman spectroscopy in the field of clinical pharmacology are expected.

Assessment of drug content uniformity of atropine sulfate triturate by liquid chromatography-tandem mass spectrometry, X-ray powder diffraction, and Raman chemical imaging.

BACKGROUND: Atropine sulfate is an anticholinergic agent for treatment of hypertrophic pyloric stenosis and is orally administrated as a triturate with lactose hydrate. Because of the low safety margin of atropine sulfate, triturate uniformity is a key safety factor. In this study, we assessed the uniformity of atropine sulfate in 1000-fold triturates prepared by wet mixing and dry mixing methods and discussed the cause of the difference in uniformity between two preparation methods. METHODS: A 1000-fold triturate of atropine sulfate with lactose hydrate was prepared by two different methods: wet mixing and dry mixing. The wet mixing was performed according to Kurashiki Central Hospital protocol and the dry mixing was a simple physical mixing by a rocking mixer. The uniformity of atropine sulfate content in aliquots of a 1000-fold triturate with lactate hydrate was assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantification. Solid-state analyses of the triturates by Raman chemical imaging and X-ray powder diffraction (XRPD) were performed to investigate the difference in uniformity. RESULTS: The LC-MS/MS quantification showed that the uniformity of atropine sulfate in the 1000-fold triturate was excellent for wet mixing but was significantly variable for dry mixing. On the basis of the Raman chemical imaging and XRPD analyses, it was indicated that an amorphous thin film of atropine sulfate coated the surfaces of the lactose hydrate particles during wet mixing and contributed to the uniformity of the triturate. In contrast, clusters of the crystalline atropine sulfate were found in the dry mixing samples. CONCLUSION: The results showed that better atropine sulfate triturate uniformity was achieved using the wet mixing method rather than the dry method and the cause of the uniformity difference between two mixing methods was indicated by the multilateral assessment.

Retrospective serological tests for determining the optimal blood concentration of voriconazole for treating fungal infection.

We investigated the optimal blood concentration of voriconazole (VRCZ) based on trough blood concentrations (C) and serological test values in patients. With regard to the regulation of VRCZ dosage (D) to maintain optimal blood concentrations, we investigated the relationship between C and D. Twenty-three patients were enrolled in the present study, and at 28 point data were analyzed retrospectively.When the beta-D-glucan or the Aspergillus antigen were decreased below the standard set values, it was evaluated as effective. The adverse events were evaluated using the Common Terminology Criteria for Adverse Events ver. 3.0. We found a significant difference (p<0.05) in the average trough blood concentration between patients in whom VRCZ was effective and those in whom VRCZ was ineffective (8.21+/-2.19 microg/ml vs. 1.01+/-0.86 microg/ml), and patients presenting with adverse events and those with no adverse events (7.64+/-2.84 microg/ml vs. 1.49+/-1.79 microg/ml). There was no significant relationship between C and D (C: D, y=0.018-2.186, r(2)=0.349).Improved efficacy and more adverse events thus occurred with higher blood concentrations. The careful regulation of the dosage must be performed while measuring blood concentration and observing for adverse events. The implementation of therapeutic drug monitoring for VRCZ is a valuable tool for achieving effective fungal infection therapy and should be aggressively investigated in future studies.