Interferon monotherapy is less effective against chronic hepatitis C when it is caused by the genotype lb virus, which is highly prevalent in Japan. For this reason, combination therapy comprising interferon and ribavirin has recently been introduced, but this new therapy often causes serious adverse effects. This study was undertaken to characterize the adverse effects in 25 patients who underwent combination therapy in the Department of Gastroenterology of Sapporo City General Hospital. All the patients complained of pyrexia and malaise in the initial stage (1 to 4 weeks) of the therapy. Adverse effects occurring in the mouth, however, such as dysgeusia, increased saliva viscosity, and stomatitis, occurred preferentially 4 weeks after the start of the therapy. In patients who discontinued the combinationtherapy, hemoglobin levels decreased significantly, by more than 30%, compared with before treatment, and the incidences of malaise, anorexia and depression were significantly higher than those in patients who completed the therapy. Further, two weeks after the start of the combination therapy, serum ribavirin levels had increased to more than 2000ng/mL, and levels at this stage tended to be higher than those in patients who completed the therapy. Therefore, to prevent patients from discontinuing such combination therapy, it is necessary to monitor adverse effects as well as hemoglobin and ribavirin levelsat the initial stage.
In the present study, a questionnaire was sent to the pharmacies of all 82 hospitals that provide advanced treatment in Japan to ascertain the current working situation of hospital pharmacists and problems associated with their working conditions. Valid responses were obtained from 61 hospitals (recovery rate : 74.4%). In their responses, 91.8% of the hospitals (56/61) said that they used a shift system. Only one pharmacist was on duty during the night shift on weekdays in 77.0% of these hospitals (n=47) and there was only one on the day shift on Sundays in 47.5% of them (n=29). As for the effect of prescription ordering systems, injection ordering systems, ampule dispensing systems, medicine conveyance systems and other automated systems, on the workload of hospital pharmacists, our questionnaire revealed that the workload of pharmacists working in the hospitals operating these systems for 18 hours or more was about 1.6 times greater than that for pharmacists working in hospitals operating them for less than 18 hours. The present study showed that a small number of pharmacists work very long hours in shifts at many hospitals. This is a problem from the viewpoint of risk management, and so there is an urgent need to improve the working conditions of pharmacists who work in shifts. Furthermore, if automated systems are operated all daylong, it is necessary to consider the workload of the pharmacists on duty.
A heat-sealing process is commonly used for the packaging of tablets and capsules. However, it can sometimes be very difficult for patients who have impaired vision or hand mobility disorders to remove medicines from such packages. These difficulties could result in reducing their drug compliance. To assess this situation, we conducted a multi-center study on the ease of opening heat-sealed packages, whose subjects were 46 patients aged over 60 with chronic diseases and 27 healthy volunteers aged over 22. On comparing medicines containing the same active ingredient in this respect, both patients and healthy volunteers preferred Bayaspirin® 100mg to Bufferin® 81mg tablets, Prednisolone® “Takeda” 5mg to Predonine® 5mg tablets, and Onealfa® 0.5μg tablets to Alfarol®0.25μg capsules. When drugs in the same category and having the same indication were compared, the order of ease ofopening was Lochol® 20mg, Mevalotin® 10mg, Lipovas® 5mg and then Lipitor® 10mg, and the healthy volunteers foundit more difficult to remove Lipovas® 5mg from its package than the other 3 HMG-CoA reductase inhibitors. For H2-blockers, both patients and healthy volunteers found Asinon capsules 150mg the easiest to remove from the package and Zantac® tablets the most difficult. By reflecting these results in the medication plans of individual patients it would be possible to improve their drug compliance.
It is necessary to carefully monitor the administration of Cyclosporine (CyA) because it has a narrow therapeutic range and its pharmacokinetics are affected by a variety of factors. Here we report a case in which the CyA concentration in whole blood was elevated accompanying deterioration in renal function. The patientwas a 54-year-old woman who had undergone bone marrow transplantation. She was given CyA (3.0mg/kg/day) and fluconazole (FLCZ, 100mg/day), intravenously and the CyA concentration was steady at the beginning. However, the serum creatinine level began to gradually increase on the 12th day following transplantation and an increase in CyA concentration was observed on the 19th day. Renal function continued deteriorating, and there was a 44% decrease in CyA clearance as compared with the time that it was steady. These results imply that the decrease in the clearance of CyA, a hepatic excretion drug, was due to renal dysfunction. Further testing revealed that the serum FLCZ concentration was elevated in conjunction with the decrease in CyA clearance. Taken together, these results suggest that the large reduction in CyA clearance was due to interaction with FLCZ, a renal excretion drug, as well as the renal dysfunction. It is therefore necessary to closely monitor the CyA concentration in such a patient.
Iron is known to interact with various foods and drugs taken at the same time and since ascorbic acid generally seems to promote the intestinal absorption of iron, we performed a retrospective medical survey using medical charts to establish the effect of ascorbic acid on patients with iron deficiency anemia taking sodium ferrous citrate. The hemoglobin levels and hematocrits of patients with iron deficiency anemia were markedly improved after taking sodium ferrous citrate containing 50 mg of elemental iron alone for 4 to 8 weeks. However, there was no difference between the hemoglobin and hematocrit results for this group of patients and another group who took ascorbic acid (200mg) in addition to sodium ferrous citrate. These results suggest that ascorbic acid does not influence the efficacy of sodium ferrous citrate when these agents are administered together for the treatment of iron deficiency anemia.
We report on the cutaneous adverse reactions of gefitinib (Iressa), an orally active, selective epidermal growth factor (EGF) receptor tyrosine kinase inhibitor that blocks signal transduction pathways, in a 19-year-old woman with recurrentmalignant glioma. When treated daily with 250mg gefitinib (p.o), the patient developed severe itching (Grade 2) and seborrheia (Grade 2) in the scalp, and acneiformeruption on the face (Grade 1) and upper limbs (Grade 1). The application offluocinonide lotion to her scalp did not improve the symptoms, but the antihistaminic ebastine was effective. These cutaneous adverse reactions result from of gefitinib's direct interference with EGF receptor signaling in the skin and further studiesshould be conducted to elucidate the mechanisms by which they occur.
To investigate risk factors of postoperative infection following cardiac surgery, we conducted a retrospective analysis of two surgical procedures, off-pump primary coronary artery bypass grafting (off-pump CABG : OPCAB) and surgery for valvular heart disease (valve operation). A total of 524 consecutive patients undergoing primary OPCAB and 262 consecutive patients undergoing a primary valveoperation, between January 2001 and December 2002, were studied. We divided the patients into two groups : those treated with cefazolin (CEZ) both before and after surgery (CEZ-not-replaced group) and those in whom CEZ was replaced by other antibiotics after surgery (CEZ-replaced group) and conducted our analysis in consideration of patient-related factors and surgical procedure-related factors. After discussing the analysis results with the respective physicians, the dosing guidelines for CEZ were changed as follows : 1) Shorten postoperative administration of CEZ to two days, 2) Switch to alternative antibiotics if outcome of WBCon postoperative day 3 indicates such necessity, and 3) Additionally administer intra-operative CEZ when surgery exceeds four hours. We also analyzed the rate of CEZ replacement with other antibiotics after surgery finding that it decreased in both groupsfor OPCAB and valve operations. From these results, we conclude that, if CEZ is also administered intra-operatively when surgery is prolonged, its administration for two days following surgery is adequate for prophylaxis against postoperative infection.
Pharmacists are responsible for supplying appropriate drug information to other medical staff from the enormous amount of drug information available. While the most common source of such information is package inserts, their content is standardized by law and the information in them is often insufficient for administration planning and determining the optimal dosage. In this study, we compared the content of the Physicians' Desk Reference (PDR) published in the USA with that of Japanese package inserts for antibiotics to evaluate the current situation of drug information provision in Japan. The PDR contained more drug information than the package inserts, its content was sufficient for administration planning and descriptions were clear. On the other hand, parts of package inserts were unclear and the information given inadequate for making administration plans. The results of this comparison suggest that the content of package inserts needs to be improved to ensure the optimal use of drugs.