[Two Cases at Community Pharmacies of Mercaptopurine Removal from a Disk-type Powder-packaging Machine by Wiping It with Water].

"Leukerin® powder 10%" containing mercaptopurine (6-MP) is an oral anticancer drug that requires careful handling. As a powder formulation, there are risks of exposure due to scattering during dispensing and possible 6-MP contamination to other drugs due to adhesion to the packaging machine. We previously reported that wiping with an alcohol-containing towel is useful for removing scattered powder after dispensing. However, it is recommended to wipe disk-type powder-packaging machines with water instead of cleaning with the alcohol-containing towel. Hence, we scattered 6-MP powder 100 mg (total amount of 6-MP: 10 mg), and then wiped with water three times using different types of cloth each time. We confirmed that third time wiping cloth did not have any 6-MP. Furthermore, we confirmed that the adhering 6-MP could be removed by wipe-cleaning (water-wiping twice and dry-wiping once) after dispensing 6-MP powder at two pharmacies that routinely dispensed 6-MP powder using a disk-type powder-packaging machine. In addition, we confirmed the adhesion of 6-MP in parts of the machine not cleaned by wipe-cleaning and also in parts that were washed only with water, in both the pharmacies. Based on the above observations, we recommend the following steps for cleaning disk-type powder-packaging machines after dispensing 6-MP powder: (1) wipe-cleaning that includes water-wiping twice and then dry-wiping once, (2) cleaning all areas of the packaging machine, and (3) wipe-cleaning with water before washing with water.

Mixture of clopidogrel bisulfate and magnesium oxide tablets reduces clopidogrel dose administered through a feeding tube.

BACKGROUND: In clinical practice, a mixed suspension of clopidogrel bisulfate and magnesium oxide (MgO) tablets is administered frequently via a feeding tube. However, there is no report on the changes occurring when suspensions of these two drugs are combined, including the effects or potential decrease in dose following tube administration. Thus, the purpose of our study was to investigate the (i) changes caused by mixing clopidogrel bisulfate (ion form) and MgO tablets and (ii) effects on the administered clopidogrel dose after passing through a feeding tube. METHODS: The molecular structure of clopidogrel generated in a mixture of clopidogrel bisulfate and a basic compound, such as sodium bicarbonate or MgO tablet, was determined by 1H-NMR after extraction and purification. The suspension of clopidogrel bisulfate tablet alone and the mixed suspension of clopidogrel bisulfate tablet and MgO tablet were passed through a feeding tube. We compared the yield of the molecular form of clopidogrel from each passed fraction. RESULTS: The substance obtained from the mixture of clopidogrel bisulfate tablet and sodium bicarbonate or MgO tablet was identified as the molecular form of clopidogrel, and chemical degradation did not occur under these conditions. In the tube passage test, the yield of clopidogrel (molecular form) from the mixture of clopidogrel bisulfate and MgO tablets was lower than that from the suspension of clopidogrel bisulfate tablet alone. CONCLUSIONS: The mixture of clopidogrel bisulfate and MgO tablets caused a considerable reduction in the administered dose passed through the feeding tube. Therefore, it is recommended to administer the suspensions of clopidogrel bisulfate and MgO tablets separately for safe and effective pharmacotherapy.

[Safe Handling Method for Splitting Azathioprine Tablets].

The immunosuppressant azathioprine (AZA) is classified as a hazardous drug. AZA contamination during tablet-splitting increases exposure risk. However, there is no study on contamination and exposure during AZA tablet splitting and dispensing. AZA tablet splitting and dispensing methods were classified based on whether tweezers are used during splitting and packaging. In Dispensing Method (1), no tweezers were used in either step. In Dispensing Method (2), no tweezers were used during tablet splitting, but were used during packaging. In Dispensing Method (3), tweezers were used in both steps. After AZA half-tablet split-dispensing, we quantified the adherent AZA removed from the tools, packaging machines, and dispensing counters by three consecutive wipings with water-dampened polypropylene cloths. A large amount of AZA adhered to the gloves used in Dispensing Methods (1) and (2), wherein tablets were placed with gloved hands, compared with Dispensing Method (3), wherein tablets were held with tweezers. Thus, the gloves must be replaced before touching the packaging paper during the final step. After three consecutive wipings, AZA was not detected at most of the sites in the third round. Thus, we recommend that (1) AZA tablet splitting should be performed while wearing gloves, (2) the gloves should be changed before packaging the half tablets, and (3) the tools, packaging machines, and dispensing counters should be wiped twice or thrice with a water-dampened cloth after dispensing.

Evaluation of Measures against Exposure during Administration of Hazardous Drugs through a Feeding Tube.

Hazardous drugs (HD), which need to be handled with care, may be administered through a feeding tube using the simple suspension method. However, instrument contamination during HD administration with the simple suspension method remains unclear. Therefore, to minimize such contamination during the simple suspension method using an injector, we propose the following exposure countermeasures method: (1) Wear two layers of gloves. (2) Prepare injectors for administration and flushing. (3) Use caps. (4) Replace outer gloves after the removal of tablets from the press-through package (PTP) sheet. (5) Handle drugs on a tray. (6) Inject while wrapping the connection site between the injector for administration and the tube with gauze. (7) Wrap the connection site between the injector and tube with gauze. (8) Do not point the injector downward. To establish whether these countermeasures method are effective, 16 ward nurses who routinely administer drugs via a feeding tube were enrolled as subjects. By visual evaluation, we compared differences in instrument contamination between a suspension using a medicine cup and administration via a feeding tube (the conventional method) and the exposure countermeasures method. Exposure with the countermeasures method under our instruction was markedly lower than that with the conventional method. Furthermore, after implementing the exposure countermeasures method, most nurses noted that caution and awareness of exposure countermeasures increased. Thus, to minimize exposure, we recommend the implementation of the exposure countermeasures method and increasing knowledge and awareness of measures against exposure.

Clinical Pharmacy Education in Japan: Using Simulated Patients in Laboratory-Based Communication-Skills Training before Clinical Practice.

The Japanese pharmaceutical curriculum was extended from four to six years in 2006. Students now receive practical communication-skills training in their fourth year, before progressing to train in hospital and community pharmacies in their fifth year. Kitasato University School of Pharmacy, Tokyo, had established a program to meet these aims before the 2006 guidance. In the present study, we discuss and evaluate the features of this communication-skills training program. This study enrolled 242 fourth-year pharmacy students at Kitasato University. Students filled out a questionnaire survey after completing the laboratory element of their undergraduate education. As part of training, students were asked to obtain patient data from a model medical chart, before performing simulated patient interviews covering hospital admission and patient counseling. These simulations were repeated in a small group, and feedback was provided to students by both the simulated patient and the faculty after each presentation. It was found that students were able to develop their communication skills through this approach. Thus, an effective system of gradual and continuous training has been developed, which allows students to acquire clinical and practical communication skills.

Comparison of the effects of single doses of elcatonin and pregabalin on oxaliplatin-induced cold and mechanical allodynia in rats.

Oxaliplatin frequently causes peripheral neuropathy. Clinical studies have indicated that pregabalin ameliorates oxaliplatin-induced peripheral neuropathy. However, pregabalin frequently causes dizziness and somnolence. We previously reported that elcatonin, a synthetic analog of eel calcitonin, attenuated oxaliplatin-induced cold and mechanical allodynia in rats. The aim of the present study was to compare the anti-allodynic effects of elcatonin and pregabalin in the rats developing the oxaliplatin-induced neuropathy. Male Sprague-Dawley rats were treated with a single dose of oxaliplatin (6 mg/kg, intraperitoneally (i.p.)) to induce cold and mechanical allodynia. We assessed the effects of subcutaneous elcatonin (20 U/kg) and oral pregabalin (30 mg/kg) on cold and mechanical allodynia by cold stimulation (8°C) to the hind paw of the rats and the von Frey test, respectively. Elcatonin reversed the effects of oxaliplatin-induced cold and mechanical allodynia in rats for a longer time period than pregabalin does. These results suggested that elcatonin might be useful for the clinical treatment of oxaliplatin-induced neuropathy.

Salmon calcitonin reduces oxaliplatin-induced cold and mechanical allodynia in rats.

Oxaliplatin is commonly used anti-cancer drugs, but it frequently causes peripheral neuropathic pain. Recently, we reported that elcatonin, a synthetic analog of eel calcitonin, attenuated the oxaliplatin- and paclitaxel-induced cold and mechanical allodynia in rats. In the present study, we determined whether salmon calcitonin also had anti-allodynic effects on oxaliplatin-induced neuropathy in rats. The rats were treated with a single dose of oxaliplatin (6 mg/kg, intraperitoneally (i.p.)). Oxaliplatin resulted in cold and mechanical allodynia. We assessed the anti-allodynic effects of subcutaneously administered salmon calcitonin (20 U/kg/d) by cold stimulation (8°C) directly to the hind paw of the rats and by using the von Frey test. Salmon calcitonin almost completely reversed the effects of both cold and mechanical allodynia. These results suggest that salmon calcitonin is also useful for treatment of oxaliplatin-induced neuropathy clinically.

Effect of synthetic eel calcitonin, elcatonin, on cold and mechanical allodynia induced by oxaliplatin and paclitaxel in rats.

Oxaliplatin and paclitaxel are commonly used anti-cancer drugs, but they frequently cause peripheral neuropathic pain. In this study, we investigated the effect of elcatonin, a synthetic eel calcitonin, on oxaliplatin- and paclitaxel-induced neuropathy in rats. The rats were treated with a single dose of oxaliplatin (6 mg/kg, i.p.) or repeated doses of paclitaxel (2 mg/kg, i.p.) on 4 alternate days. Both treatments resulted in cold and mechanical allodynia. We assessed the anti-allodynic effects of subcutaneously administered elcatonin (20 U/kg/day) by using a newly developed method to provide cold stimulation (8°C) directly to the hind paw of the rats and by using the von Frey test. Elcatonin almost completely reversed the effects of both cold and mechanical allodynia. To determine the mechanism of this anti-allodynic effect, we examined the effect of elcatonin on neuropathy induced by intraplantar injection of two organic compounds: allyl isothiocyanate (1 nmol/paw), which activates transient receptor potential ankyrin-1 channels, and menthol (1.28 µmol/paw), which activates transient receptor potential ankyrin-1 and melastatin-8. Pre-administration of elcatonin almost completely prevented cold and mechanical allodynia from being induced by both compounds. These results suggest that elcatonin attenuates oxaliplatin- and paclitaxel-induced neuropathic pain by inhibiting the cellular signaling related to transient receptor potential ankyrin-1 and melastatin-8. Thus, we conclude that administration of elcatonin may improve the quality of life of cancer patients receiving chemotherapy.

[Analysis of cardiac toxicity caused by cyclophosphamide in the H9c2 cell line and isolated and perfused rat hearts].

Cyclophosphamide is used for liver cancer, breast cancer and multiple myeloma, and the pretreatment of hematopoietic stem cell transplantation. A medium to high dose of cyclophosphamide is known to cause irreversible heart failure in some cases, and recently cardiac tamponade and pericarditis have been reported to occur when cyclophosphamide is administered for the pretreatment of hematopoietic stem cell transplantation. To test whether cyclophosphamide itself induces cellular toxicity, we investigated a toxic effect of cyclophosphamide, acrolein, a metabolite of cyclophosphamide, and doxorubicin, which is known to have cardiac toxicity, in the H9c2 cell line and the isolated Langendorff-perfused rat hearts. Cyclophosphamide itself did not have a toxic effect, whereas the toxicity of acrolein is 1, 000 times higher than that of doxorubicin in the H9c2 cell line. Acrolein, but not cyclophosphamide, reduced the left ventricular developed pressure and heart rate, and increased the left ventricular end diastolic pressure. These results suggest that the cardiac toxicity of cyclophosphamide may be caused by acrolein, one of its metabolites. Cyclophosphamide is known to cause hemorrhagic cystitis, and uromitexan was shown not to protect against the cardiac toxicity of cyclophosphamide. Development of new cardioprotective compounds is needed to administer CPA more safely.