Hypoxia‐inducible factor prolyl‐hydroxylase inhibitor (HIF‐PHI) is a novel agent for the treatment of renal anemia. HIF‐PHI increases endogenous erythropoietin production by inhibiting the degradation of an erythropoietin transcription factor. Although beneficial effects are expected from HIF‐PHI, its novel mechanism raises concerns regarding the risk of potential adverse events. The cases of hypothyroidism, which had not been reported in clinical trials, were reported after the administration of roxadustat in a real‐world setting. However, the effects of HIF‐PHIs on thyroid function have not yet been fully evaluated. This study aimed to assess the clinical impact of HIF‐PHIs on thyroid function using the Japanese Adverse Drug Event Report database, a spontaneous reporting system in Japan, because HIF‐PHIs were made available in Japan before they were available in other countries. Although a disproportionality signal for hypothyroidism was detected with roxadustat (reporting odds ratio [ROR]:22.1, 95% confidence interval [CI]:18.3‐26.7, no signals were detected with another HIF‐PHI, daprodustat (ROR:1.3, 95%CI:0.3‐5.4), and epoetin beta pegol (ROR:1.2, 95%CI:0.5‐2.7). Signals of hypothyroidism due to roxadustat were also detected regardless of age or sex. Approximately 50% of hypothyroidism cases were reported within 50 days of starting roxadustat use. These results indicate that roxadustat use may be related to the development of hypothyroidism. The need for monitoring of thyroid function should be alerted during roxadustat administration regardless of age or sex.

Cisplatin is classified as a drug with high emetic risk; thus, the use of aprepitant or fosaprepitant in addition to a 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonist and dexamethasone is recommended for antiemetic therapy. Further, hydration is required to prevent renal dysfunction, and the use of magnesium has been proposed as a part of the hydration procedure. When fosaprepitant is chosen for antiemetic therapy because the patient has dysphagia, and magnesium is added to the hydration procedure, there may be an incompatibility between the two drugs that reduces the antiemetic effect. In our hospital, in a former regimen, these two drugs were administered concurrently as premedication for regimens containing cisplatin. We varied the conditions so that in a revised regimen the two drugs did not come into contact due to pharmaceutical support, and we conducted a retrospective study to determine the difference in the antiemetic effect. The observation period was 2 years (from October 2015 to September 2017) for the former regimen group (n 89) and 2 years (from October 2017 to September 2019) for the revised regimen group (n 177). Comparison of the former and revised regimen groups revealed sex (p 0.012); anticancer drug dosage (p 0.006); and variation of premedication condition (p 0.043) as factors affected by the revised regimen. Optimization of the premedication regimen was a form of necessary pharmaceutical support to maintain the patient's QOL.

Acetaminophen is approved up to 4,000 mg per day as an analgesic agent in Japan and displays analgesic effects depending on dosage. On the other hand, acetaminophen has some interactional effects. The mechanism of the interaction between acetaminophen and warfarin has not been elucidated, and no interactional cases have been reported in Japan either. However, two cases of marked PT-INR elongation were recognized by two inpatients in our hospital, Japanese males in their 50s and 60s who were treated with concurrent chemoradiotherapy using 70 Gy radiotherapy delivered as 2 Gy daily and triweekly 100 mg/m 2 cisplatin, that had been prescribed both drugs. Each PT-INR lapsed into loss of control; the maximum for one was more than 20 which was unmeasurable and for the other, 9.48, given vitamin K2 (VK2) immediately was antagonistic to warfarin. Concomitant drugs of warfarin were promptly checked again to see if it was related to the plasma protein binding ratio and hepatic cytochrome P450 inhibition reaction. Furthermore, each liver function test was also normal. As a result of consideration on these two, the dosage of acetaminophen has possible implications. It could be caused by the active metabolite of acetaminophen, NAPQI (N-acetyl-para-benzoquinone imine), as reported by basic research of VK cycle inhibitory action; however, the mechanism is not completely clear yet so future research is required to clarify this point. In any case, it is necessary to regularly measure PT-INR through the combination of warfarin and acetaminophen.