Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are the most widely used cholesterol-lowering agents for prevention of obstructive cardiovascular events. However, statins can cause a variety of skeletal muscle problems including myopathy and rhabdomyolysis, which is characterized by an elevation of creatine kinase (CK). The occurrence of myopathy has been estimated to range from 1% to 5%. The prevalence of muscular symptoms is as high as 25% among statin users who exercise. However, the mechanism by which statins cause myopathy is not precisely known. Since exercise induces the expression of monocarboxylate transporter (MCT) 4, we focused on the association between MCT4 and statin-induced muscle injury.
This review summarizes our findings:
1) MCT4 is a pH-dependent transporter and contributes to lactate release in RD cells as a model of in vitro skeletal muscle. AMP-activated protein kinase (AMPK) activated by exercise, increased MCT4 expression level and lactate efflux by MCT4 in RD cells and rat skeletal muscle.
2) Statins reduce the number of viable cells and up-regulate MCT4 in RD cells. MCT4 knockdown suppresses statin-induced reduction of cell viability and apoptosis compared with negative control-treated RD cells.
The cytotoxicity of cerivastatin, one of the statins, is associated with intracellular acidification and caspase-3/7 activation.
3) Bicarbonate prevents cerivastatin-induced pH alteration, cytotoxicity in RD cells and muscle damage in an in vivo study.
These results suggest that both increased expression of MCT4 and disturbance of skeletal muscle cell pH homeostasis may play an important role in statin-induced cytotoxicity.
A “hospital formulation” is medicine prepared by hospital pharmacists when doctors cannot provide the medical therapy most suitable for a patient using commercial pharmaceuticals. However, as the responsibilities of pharmacists are increasing, the ability to provide hospital formulations is decreasing. The development of evidence-based hospital formulations is thus limited. Irsogladine maleate (IM) is a drug with gastric mucosa-protective properties. IM increases intracellular cyclic adenosine monophosphate levels in the gastric mucosa and activates communication between cells. Oral administration of IM has been reported to reduce the incidence of 5-fluorouracil-based chemotherapy-induced stomatitis. However, no reports have described the effects of IM when used for direct stomatitis. We therefore studied the development of an IM oral spray for stomatitis treatment and obtained evidence of direct effects.
Increases in national healthcare costs are heightening concerns for Japanese society. In recent years, the development and utilization of biosimilars (BSs) has become an area of focus because they are 23-30% cheaper. However, the use of Infliximab BS does not necessarily ensure the reduction of patient payments in Rheumatoid Arthritis (RA) cases. This paradox adversely affects the wider use of Infliximab BS. Its market penetration in Japan is less than 1%. This may indicate a significant loss for the both national healthcare scheme and patients. It is critical to identify the causes and possible remedies. We conducted a study with simulated one-year RA patient models and calculated total monthly payments for Infliximab BS and branded biologics (BBs).
Problems arise when three conditions are met: patient’s age under 70, annual income of 3.7 million yen or less, and three-dose vials daily. The main contributor to this situation is the High-Cost Medical Expense Benefit, which covers monthly payments exceeding a specified amount. This system applies to Infliximab BB users. The estimated number of patients who meet all three conditions is around 1,305 about 8% of RA patients treated with Infliximab. This shows that the majority of patients (92%) benefit from using Infliximab BS. Therefore, we do not feel that total abandonment of Infliximab BS use is justified. Our findings support that the High-Cost Medical Expense Benefit has to be adequately modified, so that BS users do not pay more for treatment than BB users.
Light emitting diodes (LEDs) are widely used in lighting applications, and several types of LEDs are on the market. Firstly, we examined the difference in the degree of color change of various medicines when using LED and fluorescent lighting; the color change of medicines in LED lighting tended to be smaller than in fluorescent lighting, as we reported previously. Next, we examined the difference in the degree of color change of various medicines in three types of LED lighting. As a result, a noticeable degree of color change was observed in the Lasix® 20-mg Tablet (Tab) and Parlodel® 2.5-mg Tab. The degree of color change was as follows: bulb color LED lighting < lunch white LED lighting < daylight color LED lighting. The results of our study suggest that one of the most suitable lighting applications for medicines in the dispensary of a medical institution is the bulb color LED lighting.
Following the publication of a guideline on the safe handling of hazardous drugs (HDs) in Japan, the issue of cost-effectiveness has been become a problem. We introduced the PhaSeal™ system in June 2015, a closed system drug transfer devices (CSTD) used for all outpatients, from preparation to administration. We retrospectively compared clinical outcomes before and after the introduction of CSTD of HDs included chemotherapy. Furthermore, we evaluated the medical fee income and the cost of providing CSTD between July and December 2015. The mean number of outpatient chemotherapy treatments per day before and after CSTD introduction was 15 ± 6 and 14 ± 5, respectively (P = 0.947). The mean preparation time by pharmacists before and after introduction was 21 ± 9 and 24 ± 9 minutes, respectively (P = 0.002). The mean time of nursing preparation before and after introduction was 29 ± 16 and 25 ± 14 minutes, respectively (P = 0.068). The mean time of patients waiting for chemotherapy before and after introduction was 36 ± 17 and 37 ± 17 minutes, respectively (P = 0.735). Based on the mean differences between the medical fee income and the cost of CSTD per month, we estimated that the annual cost associated with the introduction of CSTD for all outpatient to administer HDs was approximately JPY 21,000,000. After April 2016, we estimated that the amount of increase of the medical fee income of CSTD was approximately JPY 2,000,000 per year. These results suggest that the medical fee income should be increased so CSTD can be implemented for all outpatients.
Approximately 60% of individuals regularly purchase over-the-counter (OTC) drugs for digestive disorder treatment, and some switches from prescription to OTC (Rx-to-OTC) drugs are also made. Since many of these drugs are classified as first-class drugs, pharmacists need to ensure the safety by providing drug information. Therefore, we assessed the safety signals by determining the adverse drug reactions (ADRs) caused by Rx-to-OTC switched agents for treating digestive disorders.
The Japanese Adverse Drug Event Report (JADER) database entries from April 2004 to January 2015 for 14 Rx-to-OTC switched agents that were not prescribed for children were analyzed in adults more than 20 years of age. Hypersensitivity and hepatic disorders were considered to be serious ADRs. Signals in the data that indicated a drug-associated ADR were assessed using the reporting odds ratio (ROR). A lower-bound 95% two-sided confidence interval of > 1 indicated an ADR.
Signals for hepatic disorders were detected in the case of 2 Rx-to-OTC switched agents, ie, famotidine and rebamipide. Hypersensitivity was detected for donperidone and trimebutine maleate. In addition, most of these ADRs were expressed within 1 month of drug administration. These results suggest that pharmacists should dissuade individuals from taking drugs before medical consultation.
We previously reported that various amounts of hazardous drugs, cyclophosphamide and fluorouracil had contaminated both the inside and outside of their blister packs. However, contamination from the non-antineoplastic drug, dutasteride, which primarily has adverse reproductive effects on female healthcare workers in the clinical setting, pregnant women and their families, has not been elucidated. Here we show that dutasteride was detected on both the inside and outside of blister packs of Avolve® Capsules. The amount of dutasteride extracted from blister packs and softcapsules was measured by LC-MS/MS. In addition, dutasteride was also detected on the surface of the softcapsules. Dutasteride attached to the surface of a capsule can become attached to others by physical contact. Our data suggest that pregnant women and their families can be exposed to dutasteride attached to blister packs and the surface of capsules, and female healthcare workers in contact with Avolve® Capsules can also be exposed to dutasteride. It is necessary to take measures to prevent unintended exposure to females.
In April 2014, the Act on Clinical Laboratory Technicians, etc was revised to allow self-blood tests at community pharmacies designated as “Bioanalytical Labs.” However, fewer than 1,000 pharmacies have been designated as such and the number is decreasing. This study aimed to clarify the disincentives to the continuation of pharmacies' participation as Bioanalytical Labs and to contribute to promoting it. We sent a questionnaire to all community pharmacies designated as Bioanalytical Labs. Of the 924 questionnaires distributed, 395 (42.7%) were returned and 320 were analyzed after excluding incomplete responses. We compared burdens in pharmacy management before and after the start of Bioanalytical Lab operation. The number of “no burden” responses increased after the start of operation (P = 0.002). Some burdens such as initial costs for instruments decreased after the start of operation (all P < 0.001). More than 90% of the respondents thought that some points in the guidelines needed revision, and more than 80% reported that customers had asked them for medical advice, which the guidelines prohibit pharmacists from providing. A significant correlation was found between those who thought that the guidelines needed revision and those who had been asked by customers for medical advice (P = 0.003). Our findings indicate that many disincentives that have an impact before the start of operation did not become burdens thereafter. However, many customers asked for medical advice that pharmacists may not provide. It seems necessary to reconsider this aspect of the guidelines in order to suit customers' needs.