Nicardipine hydrochloride injection, a dihydropyridine calcium channel blocker, is an acidic drug. The package insert recommends that nicardipine injection should be administered at the concentrations of 0.01-0.02%. However, the drug often induces venous irritation despite infusion at the recommended concentrations in the intensive care unit (ICU) at Kyushu University Hospital. Therefore, we retrospectively investigated the incidence and risk factors of venous irritation in ICU patients. Univariate and multivariate analyses revealed that the administration time and infusion rate of the drug were significantly related to venous irritation (P<0.05). Patients who were infused with nicardipine injection (administration time: more than 24 h, infusion rate: more than 45 mL/h) developed the venous irritation frequently (7 of 9, 77.8%). In the case of infusion of nicardipine injection for more than 96 h, the patients experience severe vascular damage and needed for treatment with medicine such as topical steroids. These results suggest that the administration time and infusion rate are involved in nicardipine injection-induced venous irritation, and it is necessary to pay attention to these factors as well as observing the instructions in the package insert.
Docetaxel is an extensively used taxane, frequently associated with hypersensitivity reactions (HSR). We examined whether the dilution concentration affects the incidence rate of HSR, and set up a concentration that can control HSR. We also established management of HSR that were caused by docetaxel. Retrospective analysis was performed at a single institution in 471 consecutive patients treated with the regimen, including docetaxel for breast cancer, gastric cancer, non-small-cell lung cancer, prostate cancer and skin cancer from 2006 to 2011. Among 471 patients, 90 were in the 250 mL group and 381 were in the 500 mL group. The rate of HSR was 14.4% in the 250 mL group vs 2.4% in the 500 mL group (P<0.01). Regarding the duration of HSR, there was no significant difference between the two groups (1.69 ± 0.75 cycles vs 2.22 ± 1.71 cycles). The seriousness of HSR was similar in the two groups (250 mL groups; G1:61.5%, G2:30.8%, G3/G4:7.7% vs 500 mL groups; G1:77.8%, G2:11.1%, G3/G4:11.1%). Moreover, no difference was found in the rate of HRS below 0.02 w/v% standard concentration, when all patients were divided into another two groups (above the standard concentration; Above Group, below the standard concentration; Below Group). In conclusion, our present data suggest that the dilution concentration of docetaxel strongly affects the rate of HSR. Moreover, if the dilution concentration of docetaxel is below 0.02 w/v% (cutoff value), it is suggest that HSR can be controlled. These findings show that the dilution concentration of docetaxel can become a tool that for controlling HRS in addition to the existing premedication.
In this study, we investigated the in vivo distribution of insoluble fluorescent microparticles administered to rats through the central vein. We previously reported that the IMs increased by mixed operation of some injections. The number of 10-25 μm insoluble microparticles was 41 ± 1 /mL. Therefore, the daily 10-μm fluorescent microparticle dose was set at 2000/day for the nutritional solution dose of 50 mL/day required to maintain the rats. The fluorescent microparticles were administered by bolus injection into the central vein on Days 1, 2, and 3. A fluorescence microscope was used to assess frozen thin sections of each organ that were prepared on Day 4 and urine samples. A large number of fluorescent microparticles were found in the lung tissue, with 1-5 particles in each of the 20-μm thick and 25-mm2 area sections. In 20-μm thick and 50-mm2 area kidney tissue sections, the number of observed fluorescent microparticles ranged from 0.1 to 0.2. No fluorescent microparticles were detected in tissue samples from the veins, cerebrum, cerebellum, heart, or liver. The total number of fluorescent microparticles excreted in the urine was 283.4 ± 113.0, which only accounted for approximately 4.7% of the dose administered over the 3-day period. These findings suggest that 10 μm insoluble microparticles administered intravenously, accumulate mainly in the lungs and kidneys and are excreted at low levels in the urine.
Orally disintegrating (OD) tablets have become widely used in clinical practice for the purpose of enhancing patient convenience and compliance. However, for 0.2-mg tamsulosin hydrochloride OD tablets packed by an automatic tablet packing machine under humid conditions, there is insufficient information about the quality of the tablets after the packages are opened and they are dispensed. The stability of tamsulosin hydrochloride OD tablets was examined after storage for 24 hrs, 14 days after opening the tablet packages, and 28 days after one-dose packaging of 5 companies under humid (25℃, 75% relative humidity) and non-humid conditions. After being stored under humid conditions for 24 hrs and 14 days after opening the tablet packages, the OD tablets of 2 companies were greatly affected in terms of their thickness, weight, and hardness as compared with the packed tablets that did not come into contact with humidity. Next, the tablets of one company stored for 28 days after one-dose packaging were found to be greatly impaired in relation to their hardness and friability, with the tablets partly broken along their edges. In conclusion, 4 products could be dispensed by an automatic tablet-packing machine and preserved using one-dose packaging under humid conditions. However, one among the 5 tested products should be used carefully in storage under humid conditions.
Bendamustine is an anti-cancer drug approved for relapse or refractory indolent B cell lymphoma. Although it is a promising drug because it shows a different activity pattern from other alkylating agents and a lack of crossresistance with them, there is insufficient evidence to standardize the regimen including supportive care, particularly at outpatient cancer chemotherapy. In our hospital, bendamustine (120 mg/m2) was administered to a patient with follicular lymphoma. Cycle 1 treatment was performed under hospitalization, followed by cycles 2 to 4 under outpatient cancer chemotherapy. For prophylaxis of nausea and vomiting, azasetron, dexamethasone and aprepitant were used. At outpatient cancer chemotherapy, dexamethasone was orally administered on days after bendamustine injection. No nausea or vomiting was observed throughout all cycles. However, on cycle 1, myelosuppression including grade 4 leukopenia and grade 2 thrombocytopenia were observed. Therefore, the dosage of bendamustine on cycles 2 to 4 was reduced to 90 mg/m2. During outpatient cancer chemotherapy, mild myelosuppression was observed, but chemotherapy could be achieved without delay by treatment with granulocyte-colony stimulating factor (G-CSF) or antibiotics. In this case, the bendamustine regimen could be safely performed without severe adverse events except myelosuppression, indicating that this report may be a good reference in the management of supportive care for safe administration of bendamustine.
We investigated which antiemetic treatment patients selected during epirubicin /cyclophosphamide (EC) therapy for breast cancer, and assessed the antiemetic efficacy of each treatment using the MASCC Antiemesis Tool (MAT) completed by the patients. After patients received an explanation of antiemetic treatments, including their pharmaceutical prices, they selected and used one of the following four treatments: granisetron+dexamethasone (A), granisetron+dexamethasone+aprepitant (B), palonosetron+dexamethasone (C), or palonosetron+dexamethasone +aprepitant (D). During the first cycle of EC therapy, 50 patients selected one of the four treatments, and morepatients selected Treatments B and C than others: Treatment A was selected by 9 patients (18%), B by 18 (36%), C by 17 (34%), and D by 6 (12%). A total of 198 antiemetic treatments were performed during four cycles of EC therapy: 27 treatments (13.6%) of Treatment A, 81 treatments (40.9%) of B, 62 treatments (31.3%) of C, and 28 treatments (14.1%) of D. Comparing results between Treatment B and C groups, antiemetic rates in acute and late-onset periods and complete response (CR) rates in acute and entire periods in Treatment B group were superior to those in Treatment C group. The results show that none of the treatments provided sufficient nausea control. Since the usefulness of aprepitant, a new antiemetic drug, was demonstrated, but the superiority of palonosetron to granisetron was not determined, and also taking the cost to the patient into consideration, a combination of aprepitant and dexamethasone with one selected 5-HT3 receptor antagonist is recommended.
Non-steroidal anti-inflammatory drug (NSAID) patches tend to be prescribed in larger amounts than are actually used and surplus patches are often kept at patients' homes. Improper use of these patches without the advice of healthcare professionals might result in serious adverse effects. This study investigated patients' opinions and requests regarding the prescribed amount of NSAID patches, and their intended use of surplus patches. A web-based questionnaire survey was conducted on patients who had been prescribed NSAID patches within the previous year. There were 618 respondents. Patients who described the amount of patches prescribed as “just the amount needed" and “quite or somewhat excessive" amounted to 41%and 40%of the respondents, respectively. Forty-three-percent of respondents had at some time requested a larger prescribed amount or an additional prescription. Sixty-four-percent of them received the prescription they requested. Also, 61 % of respondents had unused NSAID patches at their homes, and many of them intended to use these patches as they felt necessary. Patients who believed that NSAID patches do not induce side effects amounted to 24%, while 54%of patients had at some time suffered symptoms possibly due to systemic or local side effects of NSAID patches. Considering the above results, healthcare professionals should provide suitable and sufficient information about NSAIDs patches to patients, and take steps to minimize the numbers of unused patches remaining at the patients' homes in order to avoid improper use of NSAID patches and to reduce medication costs.
We established a pharmaceutical outpatient clinic at the International University of Health and Welfare Mita Hospital. In the clinic, pharmacists provide mainly pharmaceutical care for cancer outpatients based on prescriptions from a doctor, and then feed back the contents of medication counseling and information about patients to doctors. In this study, we evaluated the role of the pharmaceutical outpatient clinic. From April to July 2011, we investigated retrospectively the contents of feedback from pharmacists to doctors. The contents consisted of three types of information such as medication counseling, history of side effects and allergy, and uneasiness from patients. Most of this information was on side effects. Approximately 42% of uneasiness from patients was about the side effects of chemotherapy. Furthermore, we conducted a questionnaire survey in 62 cancer outpatients that gave informed consent during the period as mentioned above. The results showed that the degree of understanding of drugs on treatment and prevention of the onset of side effects after consultation was markedly improved compared with those before consulting. Many patients (50/62) felt “uneasiness about treatment" and “some uneasiness" before consultation. However, 88.0% (44/50) of them noted that their “anxiety was eased" after consultation. The degree of reduction in uneasiness in patients with stage Ⅰ and Ⅱ breast cancer was larger than that with stage Ⅲ and Ⅳ. In conclusion, it is suggested that the clinic may play a role which makes it possible to enable cancer outpatients to participate in medical treatment with ease, in addition to enabling support for doctors.