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At Oita University Hospital, we switched our usage of pemetrexed(PEM)from brand-name to generic drugs. We conducted a comparative study of the preparation efficiency and therapeutic safety with the brand-name product and examined the economic effect thereof. The incidence of adverse drug reactions was investigated retrospectively using electronic medical records for patients who received PEM brand-name and generic drugs at our hospital between April 2021 and December 2022. The preparation time per mg was significantly shorter in the generic group at 0.17(0.08-0.38)seconds compared to 0.34(0.15-0.94)seconds for the brand-name group(p<0.01). Regarding the safety comparison, none of the 13 eligible patients developed new hematologic or non-hematologic toxicities of Grade 2 or higher after switching to the generic product. The switch to generics had an economic impact of 7,369,278 yen during the study period. The results suggest that switching from brand-name to generic products is reasonable from the perspectives of therapeutic safety and economic benefits, as well as the expected improvement in preparation efficiency.

We report the case of a 72-year-old female who underwent laparoscopic total gastrectomy for gastric cancer. The pathological diagnosis was pT3, N1, M0, pStage II B. She received adjuvant chemotherapy with the TS-1®combination OD tablet, beginning 48 days after gastrectomy. The first course was stopped at day 7 because of neutropenia. The dose was decreased, a second course was started, and the patient completed her second course without neutropenia. After completion of the second course, we discovered that she had taken generic drugs(NKS-1®combination OD tablet)during the second course. She was enrolled in a clinical trial in which the administration of generic drugs was not permitted, as per the protocol. Beginning with the third course, we once again treated her with TS-1, and we observed a return of neutropenia in every subsequent course. We decreased the dose of TS-1 and changed the administration schedule each time. She exhibited no neutropenia only when using the generic S-1 formulation. It is possible that the anti-tumor effect of the generic S-1 formulation, and its associated adverse events, are not identical to the innovator formulation.

Cisplatin (CDDP) is a key drug in the systemic treatment of various solid tumors. Brand-name CDDP may differ across generic formulations considering various clinical parameters. Therefore, in this study, we aimed to assess the safety of a generic CDDP formulation. To compare brand-name CDDP with a generic formulation, the incidence of adverse events, especially renal toxicity, was investigated in 500 patients with thoracic malignancies who received chemotherapy with more than 60 mg/m2 of either brand-name or generic CDDP. We compared the maximum serum creatinine (Cr) level after chemotherapy in the 2 groups. The correlation coefficients between the pretreatment Cr and the maximum Cr after CDDP administration did not differ between brand-name CDDP and generic CDDP (0.610 and 0.644, respectively; p=0.528). Furthermore, the correlation coefficients did not differ in subgroup analysis according to sex or adjuvant therapy. The severity of adverse events was similar in the 2 groups. In conclusion, generic CDDP can safely be used as an alternative to brand-name CDDP in the clinical setting.

Aggravation of asthmatic response (asthmatic attack, 2 cases) and adverse events (tremor, 1 case) due to a switch from a brand-name tulobuterol tape to a generic tape were recently reported. These changes disappeared after reformulation from generic to the brand-name tape. To investigate this issue, we conducted a questionnaire survey on changes of asthmatic response, adverse events and product usability due to a switch between tulobuterol tapes. We identified 44 cases (18 from doctors, 26 from pharmacists) in which changes of asthmatic response or adverse events had occurred due to a switch between tulobuterol tapes. Aggravation of asthmatic response had occurred in 30 cases and adverse events in 21 cases due to switch from brand-name tulobuterol tape to generic tape. As regards change of product usability, we obtained 96 relevant responses (18 from doctors, 78 cases pharmacists), and the major response was that generic tulobuterol tape peeled off the skin more easily than did the brand-name tape (60 cases). These results suggest that changes of asthmatic response, adverse events and product usability should be carefully monitored when switching tulobuterol tapes.

The use of injectable generic antineoplastic agents has been increasing. Few studies have compared the quality and adverse reactions of generic and branded antineoplastic agents; and therefore, generic agents have not gained wide acceptance. Paclitaxel injections, which are used for treating solid cancers, are being marketed by some companies in Japan. The degree of hypersensitive reactions to these drugs may vary because of the differences in chemical properties of the polyoxyethylene castor oil that is used as a solvent in the paclitaxel preparations. Therefore, we investigated the incidence of pulmonary edema occurring as a hypersensitive reaction in rats administered branded and generic paclitaxel injections. Moreover, we compared the chemical properties of these preparations. We found that the pH of branded and generic paclitaxel preparations diluted with saline was different. This difference in pH may be attributed to a difference in chemical properties from the additive. We observed no significant differences in pulmonary vascular permeability, arterial partial pressure of oxygen, or leakage of protein in the pulmonary alveolus, between paclitaxel preparations administered to rats. These results suggest that both paclitaxel preparations induced pulmonary edema of a similar level in rats, irrespective of the differences in their chemical properties.

The purpose of this study was to compare the transdermal transfer profiles of brand and generic tulobuterol patch formulations and to evaluate possible changes of in vivo kinetics resulting from increased transdermal transfer by means of pharmacokinetic analysis using reported in vitro drug release rate data and plasma drug concentration profiles. On the assumption that the transdermal transfer rate constant (k2) would be constant (independent of formulation), the drug release rate constant from patch formulation (k1) was predicted to be almost equal to the k2 value (k1≈k2) in the brand formulation, but 2- to 4-fold higher than the k2 value (k1>k2) in the two generic formulations. Under normal conditions, there would be no marked difference in the plasma concentration profiles among the formulations. However, under conditions where transdermal transfer is increased (that is, higher k2), the plasma tulobuterol concentration was predicted to increase more rapidly, with higher C(max), and then to decrease more rapidly in the elimination phase after applying the generic formulations compared with the brand formulation. These different behaviors would be seen because the transdermal transfer of the generic formulations would be affected by k2, whereas k1 is still rate-determining for the brand formulation. These results suggest that bronchial asthma patients with risk factors for impaired skin barrier function, including atopic dermatitis, long-term treatment with steroids, and advanced age, should be carefully monitored for reduced treatment efficacy or adverse drug reactions after application of rapid-release generic tulobuterol patch formulations.

We recently encountered a case of autoimmune hepatitis whose symptoms worsened after switching from a brand name to a generic version of prednisolone. The patient was a 46-year-old woman. She was admitted because of elevation of alanine aminotransferase (ALT) levels during follow-up sessions. We diagnosed worsening of autoimmune hepatitis and increased the medication dose of prednisolone, which resulted in a quick normalization of serum ALT levels. When the prednisolone medication was switched from a brand name to a generic version, the serum ALT levels again increased. We concluded that switching from a brand name to generic version of the drug was one of reasons for the elevation in the serum ALT levels. Although most generic drugs are considered to be useful, it is important to carefully observe patients to confirm that an equivalent effect is obtained after switching from a brand name to a generic drug.

Calcium channel blockers are most commonly used in hypertensive patients in Japan. However, information on the efficacy and safety of generic calcium channel blockers is insufficient. The objective of the present study was to retrospectively evaluate the efficacy and safety of manidipine hydrochloride in 21 essential hypertensive patients (mean age; 70.6+/-10.6 years, male/female; 14/7) in Sendai Postal Services Agency Hospital who were switched (substituted) from a brand product (Calslot) to a generic product (Manidip). For this retrospective study, we used data from patient medical records and drug prescription information. Data from patients who were taking both types of manidipine hydrochloride, whose regimen were not changed for > 6 months before and after switching, and who provided informed consent were included in the analysis. Control values of blood pressure were not significantly different between before and after substitution (systolic/diastolic; from 137.9+/-9.1/78.7+/-5.4 mmHg to 137.3+/-9.1/77.8+/-6.3 mmHg, p=0.73/p=0.36). The level of patient compliance for the antihypertensive drugs was also not different between before and after substitution (from 94.0+/-8.8% to 93.1+/-9.6%, p=0.72). There were 8 cases of adverse effects before substitution and 4 after substitution. No patient stopped taking the generic drug due to an adverse effect. In conclusion, significant differences in the efficacy, safety, and patient compliance were not observed between the brand product and generic product among patients who were switched from the brand product to the generic product.

Limited use of generics in Japan has been justified on the basis of problematic quality, distribution and information. Of these three problem areas, the state of provision of information in particular has never been objectively evaluated. We therefore sought to evaluate information according to its necessity and importance to medical practice. To establish criteria for evaluation, we weighted 36 separate pieces of drug information found in package inserts and interview forms according to necessity and importance, based on the results of a survey of nationwide medical institutions with DI offices. We then used the evaluation criteria to evaluate currently available drugs with 20 or more products per formulation. We evaluated 14 formulations (324 products). Generic drugs were found to have 25.3+/-18.7 to 46.1+/-14.2% (Mean+/-S.D.) the information of brand name drugs when products were compared for quantity of information by formulation. However, comparison according to manufacturer returned a larger range of variation at 14.4+/-8.6 to 64.3+/-14.2% (Mean+/-S.D.). These data reveal that manufacturer differences play a large role in the provision of drug information. Drug information was also compared separately by category for both brand name and generic drugs. Generic drugs were found to have insufficient information on clinical data, pharmacokinetics, safety, side effects, and nonclinical tests. Brand name drugs also scored low points for information on pharmacokinetics. It is imperative that both brand name and generic drugs provide more information on pharmacokinetics.