Cancer is the major cause of death in Japan; hence, countermeasures against cancer are conducted as a national policy. Although the development in the field of cancer chemotherapy has been significant, it is also complicated. Therefore, pharmacist intervention is essential to ensure that the patients receive safe and appropriate medication. There are multiple stages of cancer chemotherapy, and these include working out the chemotherapeutic regimen, prescribing the regimen, checking the prescription, mixing the preparation of anticancer drugs, explanation to patient, and clinical evaluation of therapy. Hence, we conducted wide-ranging studies in this field. We studied proper use of antiemetic drugs, which were administered prophylactically against chemotherapy-induced nausea and vomiting in working out the chemotherapeutic regimen, and we developed a safe and efficient method by using computer regarding prescription checking and mixing preparation of anticancer drugs. In addition, we evaluated the effectiveness of chemotherapy against standard therapy. These study results could provide us with useful knowledge regarding the development of safe cancer chemotherapy and confirm the effectiveness of therapy, and we could feed back these outcomes into the clinical setting. The results revealed that when problems are resolved because of pharmacist intervention in clinical practice, the pharmacist could support the medical examination of the physician, obtain practical results directly linked to the benefit of the patient, and contribute towards the development of safe and effective cancer chemotherapy. Since the need for pharmacists in clinical practice is increasing, our results would provide essential information regarding the contribution of pharmacists to cancer chemotherapy.
The lack of commercially available oral dosage forms is an ongoing problem in drug treatment for pediatric patients. To adjust the dose and protect medical staff from drug exposure, an oral liquid dosage form can be prepared. However, information about its long-term stability and appropriate method for daily drug dispensing are limited. Valganciclovir for cytomegalovirus infections (including pre-emptive therapy) is treated for a long period. The present study investigated the stability of a valganciclovir oral liquid suspension and the development of a simple dispensing method. Triplicate suspensions of valganciclovir 30 mg/mL (as the hydrochloride salt) were prepared from commercially available tablets in reverse osmosis water. The suspensions were subjected to stability testing at room temperature or 2 - 8℃ for up to 14 days. The valganciclovir content of the tablet suspensions decreased during the storage period. Ganciclovir and L-valine, the degradation products formed from the hydrolysis of valganciclovir, were observed immediately after suspension. In acidic solutions prepared using dilute hydrochloric acid solution, the contents of valganciclovir decreased depending on the pH values. Less than 10% degradation occurred in pH 1.8 and 2.8 for 14 days. To make it easier for pediatric patients to take the drug, suspensions using a mixture of simple syrup and dilute hydrochloric acid solution (pH 2.8) or a mixture of simple syrup and citric acid hydrate (pH 2.8) were prepared. These suspensions were also stable for 14 days at 2 - 8℃. These formulations offer the benefit of a simple compounding procedure with a product that is already available in most pharmacies.
Eicosapentanenoic acid ethyl ester (EPA-E) formulation is a drug derived from fish oil. Some EPA-E formulations have a special odor depending on the manufacturing process and the type of sardine raw materials used. This odor affects the compliance of some patients. In this study, we report our assessment of the odors in each EPA-E formulation with gas chromatography/mass spectrometry (GC/MS). We used 3 lots of an original drug and 5 generic EPA-E formulations. EPA-E formulations were incubated at 40℃ in the absence of light. We collected the volatiles for 24 h immediately and 7 days later. The collected volatiles that were ultrasonically extracted with dichloromethane were used as GC/MS samples. We estimated the components on the basis of the fragment pattern and peak retention time on GC/MS. We performed principal component analysis (PCA) by using the peak area and 2-dimensional mapping, and evaluated the results. There was no change in the appearance of any of the formulations at 7 days, compared at the beginning of the experiment. However, the GC/MS measurements revealed the presence of 1-heptadecanal and 1-eicosanal, which were presumed to be oxidation decomposition products, in some formulations. These products were predicted to be the source of odors, and their intensities increased after 7 days. This difference was observed in the score plot between the 6 formulations as a result of PCA. The odors due to the decomposition products may influence the compliance of patients, and a detailed examination will be required.
From the viewpoint of health and safety, it is important that healthcare workers are not exposed to anti-cancer drugs during preparation of injections and administration to patients. In order to evaluate current procedures, we conducted a survey on handling of anti-cancer drug injections by hospital nurses in 2000 randomly selected hospital facilities throughout Japan by means of a mail questionnaire. Nurses were requested to complete the mailed questionnaire, which included questions regarding the facilities, equipment, systems and procedures of anti-cancer drug injections. Valid responses were obtained from 733 facilities. Among them, 385 facilities offered chemotherapy with anti-cancer drug injections. In approximately 30% of such facilities, nurses prepared anti-cancer drug injections. Further, nurses administered the anti-cancer drug injections in almost all of these facilities, suggesting that their risk of exposure was greater than that of pharmacists. We found that only a few hospitals currently take precautions to prevent exposure, such as wearing protective equipment and following specific procedures. Less than 50% of the facilities provided training for nurses in anti-cancer drug handling practices, and pharmacists were involved in only approximately 20% of the facilities. The nurses considered that pharmacists should prepare anti-cancer drug injections, inform them of the risk of exposure to anti-cancer drugs, and also advise them about appropriate handling. These results suggest that pharmacists should take the lead in promoting safe and appropriate handling of anti-cancer drug injections.
We report a case study of a patient with diarrhea caused by the additive D-sorbitol in a commercialized product, acetaminophen syrup. The patient was a man in his seventies diagnosed with laryngeal cancer (right glottic poorly differentiated squamous cell carcinoma, cT4aN2M1 Stage C). He had been treated with acetaminophen syrup to alleviate the pain in his throat caused by radiation therapy for his laryngeal cancer. Immediately after administration of the acetaminophen syrup, he suffered from diarrhea. This medication was discontinued and replaced by acetaminophen granules and his diarrhea disappeared. The package insert for the acetaminophen formulation dispensed in Japan reads as follows: “Abdominal pain and diarrhea may be seen as side effects associated with high doses of acetaminophen. There is a risk that this side effect may not be distinguished from the gastrointestinal symptoms associated with upper respiratory infection, therefore this medication should be administered with care with careful patient observation.” In this case, we found that the cause of the side effect diarrhea was highly likely to be the additive ingredient D-sorbitol. This side effect may depend on the age and condition of the patient but should be considered when choosing acetaminophen syrup formulations.
In cases of combination therapy, it is deemed that patients receiving a large amount of oral medication do not adhere to instructions from their physicians. Since 2006, fixed-dose combination (FDC) of hypertension agents has been innovated in practice to improve patients' medication adherence. Even though FDC therapy has had remarkable effects on hypertension, there are concerns about harmful interactions between each of the drugs. The aim of our study is to reveal the adverse events of FDC of angiotensin receptor antagonist (ARB) and hydrochlorothiazide (HCTZ). We analyzed adverse events using data from the Japanese Adverse Drug Event Report database (JADER) from April 2004 to September 2013. The adverse events surveyed were hypokalemia, hyperkalemia, hyponatremia and hyperuricemia. We calculated the Reporting Odds Ratio (ROR) from the number of reports that were extracted from the database and evaluated. During the period analyzed, 285,992 adverse events were reported to JADER; 270,491 items (94.6%), excluding ambiguous data or missing data, age and gender, were used in the analysis. A signal was detected for all the adverse events that were included in this study. Therefore, there is considered to be a need to monitor the clinical laboratory values, such as electrolyte levels, for patients taking ARB/HCTZ FDC.
Lithium carbonate has a narrow therapeutic index. Therapeutic drug monitoring (TDM) is essential for safe and effective lithium therapy. The dose of lithium carbonate administered and renal function were previously suggested to be important variables that affect serum lithium concentrations. Information regarding the co-administration of drugs that may affect serum lithium concentrations is limited. Therefore, the aim of the present drug interaction study was to examine the effects of the co-administration of antipsychotic drugs on serum lithium concentrations. A retrospective analysis was performed on 124 patients prescribed lithium carbonate at the Department of Psychiatry, Shiga University of Medical Science Hospital between January 2013 and March 2014. Serum lithium concentrations were significantly higher in patients co-administered antipsychotic drugs than in those not receiving antipsychotic drugs: 0.95 ± 0.41 mEq/L and 0.79 ± 0.27 mEq/L, respectively (P = 0.012). A multiple linear regression analysis was used to produce the following prediction equation for serum lithium concentrations: serum lithium concentration = 0.001 × lithium carbonate dose (mg) － 0.004 × Creatinine clearance (Ccr) (mL/min) + 0.123 × drug + 0.652 (with the co-administration of antipsychotic drugs:drug = 1, without the co-administration of antipsychotic drugs:drug = 0). R2 was 0.296. These results suggest that the co-administration of antipsychotic drugs is a risk factor for elevated serum lithium concentrations in addition to the dose of lithium carbonate administered and renal function.
We examined the tendencies of topical adverse effects caused by different dermatological formulations of diclofenac based on the results of our previous study. In patients with adverse effects expressed by gel (n = 64) and tape formulation (n = 174), the most common adverse effect was contact dermatitis, accounting for 59.1% and 80.0%, respectively. The peak month of adverse effects of the gel group was in May, and the peak month of adverse effects of the tape group was in August. We divided the subjects into two groups: elderly and young people and investigated the number of adverse effects and the relative incidence of adverse effects for each group. As a result, the incidence of the young people in the gel group was extremely high in March. In the elderly group, the adverse effects peaked in May, which suggests that they contribute to the peak of the total adverse effects in the gel group through the year. On the other hand, the incidence in the elderly group is higher than that in the young group in each month, and the peaks of incidence were in August and December in the tape group. In both the elderly and young groups, the peak of incidence by tape formulation was in August and the difference between the two groups was remarkable in December. In view of these results, the topical adverse effects of non-steroidal anti-inflammatory drug dermatological formulations could be reduced by the pharmacist providing suitable advice on medications considering the season and patient background, such as age.