Pediatric formulations of cardiovascular drugs are limited, and tablets are often crushed to create individualized doses. In clinical practice, pre-processed crushed formulations may be stored for later use; however, information on their long-term physicochemical stability remains limited. This study evaluated the storage stability of a crushed formulation of tadalafil, a drug used for pediatric pulmonary arterial hypertension (PAH). Tadalafil (TAD) 20 mg tablets were crushed, sieved, and mixed with lactose monohydrate to prepare a crushed tadalafil formulation (cTAD, 40 mg/g). TAD crystals were used as controls. Samples were stored for 90 d at 25 °C with 57.6 ± 0.4
There are no case reports or epidemiological studies on the use of febuxostat, a drug used to treat hyperuricemia, during pregnancy or breastfeeding. We encountered a case of familial juvenile hyperuricemic nephropathy in which the patient required febuxostat during the perinatal period. This case provides valuable insights into placental and breast milk transfer of febuxostat. A 30-year-old woman presented with familial juvenile hyperuricemic nephropathy. She strongly desired to have children. She was found to be pregnant while her condition was being controlled with febuxostat 40 mg/day and sodium bicarbonate 500 mg/day. When pregnancy was confirmed, the patient was 9 weeks pregnant. Following consultation, febuxostat administration continued during pregnancy. The patient gave birth at 38 weeks of gestation. The maternal plasma concentration of febuxostat immediately prior to delivery (before medication) was 169 ng/mL, and the umbilical cord blood concentration at birth (4 h after medication) was 154 ng/mL. No major congenital abnormalities were observed at birth. The patient chose to breastfeed after delivery. She continued taking 40 mg/day of febuxostat orally. Febuxostat concentrations in breast milk immediately before dosing and at 1, 3.5, 7 h after dosing were 37, 40, 58, and 81 ng/mL, respectively. At the one-month checkup, a deformity of the infant’s second toenail was noted. However, its association with a congenital malformation could not be confirmed, and there were no functional abnormalities. No problems with the infant’s growth or development were observed. The patient continued to febuxostat throughout pregnancy and subsequently gave birth. Further data are required to draw conclusions regarding the risks to infants associated with febuxostat use during the perinatal period.
Del Nido cardioplegia is a single-dose myocardial protective solution that is widely used in pediatric cardiac surgery. In Japan, several modified formulations have been developed because the original Plasma-Lyte A-based formulation is not available. The original formulation remains stable during refrigerated storage. However, the stability and sterility of the Chikamori-modified del Nido cardioplegia solution remain unknown. Therefore, this study evaluated the physicochemical stability and sterility of the Chikamori-modified del Nido cardioplegia solution during refrigerated storage. Three batches of the Chikamori-modified del Nido solution were prepared aseptically and stored in the refrigerator. To assess electrolytes (sodium ion, potassium ion, chloride ion, magnesium ion, calcium ion, and bicarbonate ion), pH, osmolality, and lidocaine concentration, samples were collected on days 0, 7, 14, 21, and 28. To simulate clinical practice, 1 mL of 8.4
Chemotherapy-induced nausea and vomiting (CINV) has become less visible than in the early era of cytotoxic chemotherapy, but it remains a clinically meaningful toxicity in cancer pharmacotherapy. Although vomiting is now often preventable with 5-hydroxytryptamine-3 receptor antagonists, neurokinin-1 receptor antagonists, dexamethasone (DEX), and olanzapine (OLZ), nausea, delayed and persistent symptoms, treatment-related burden, and symptoms associated with antibody-drug conjugates and oral anticancer agents remain important clinical challenges. These residual problems require systematic symptom assessment and continued optimization of supportive care in routine practice. This narrative review summarizes major developments in antiemetic therapy and places pharmacist-led and pharmacist-involved clinical studies within the broader international evidence base. The review focuses on evidence underpinning major antiemetic guidelines, randomized phase II and phase III trials, and selected prospective studies that address current questions in practice. Key topics include guideline-consistent prophylaxis, gaps between evidence and routine care, low-dose OLZ, carboplatin-based chemotherapy, DEX-sparing strategies, antibody-drug conjugate-induced nausea and vomiting, oral anticancer agents, patient-reported outcomes, electronic monitoring, and risk-based prophylaxis. Particular attention is paid to how the interpretation of benefit changes when nausea control, total control, treatment burden, daily functioning, and longitudinal symptom patterns are considered. Together, these studies illustrate a practice-to-evidence-to-implementation pathway in which routine clinical observations are translated into multicenter supportive care studies, evidence synthesis, guideline contributions, and individualized care. Antiemetic optimization is no longer limited to adding more antiemetic drugs. It includes selecting the appropriate intensity and duration of prophylaxis, reducing avoidable treatment-related burden, extending monitoring beyond 120 h when necessary, and using patient-level risk to guide escalation or de-escalation. Pharmacists can contribute by implementing guideline-based prophylaxis, detecting uncontrolled nausea and vomiting in routine cancer care, designing multicenter supportive care studies, and translating evidence into practical clinical pathways. The central message is that clinical pharmacy can function as a bridge between guideline implementation, patient-reported monitoring, evidence generation, and individualized care.
Imeglimin is an oral antidiabetic agent for type 2 diabetes that is primarily excreted unchanged in the urine. Although the development of lactic acidosis has not been reported in clinical trials, clinical data regarding the safety of imeglimin in the setting of progressive acute kidney injury (AKI) remain limited. A 46-year-old man was receiving imeglimin 1000 mg twice daily and teneligliptin 20 mg once daily for type 2 diabetes. Losartan was initiated on Day − 6, and contrast-enhanced computed tomography for preoperative evaluation was performed on Day − 5. On Day − 4, his serum creatinine level increased from a baseline of 0.77–0.84 mg/dL to 1.37 mg/dL; however, imeglimin was continued at the same dose. On Day − 1, he experienced nausea and hypoglycemia, leading to the discontinuation of both imeglimin and teneligliptin. On Day 0, he presented with a pH of 7.233, lactate level of 5.6 mmol/L, serum creatinine of 5.15 mg/dL, and blood glucose of 58 mg/dL. He was admitted to the intensive care unit for lactic acidosis, severe renal impairment, and hypoglycemia. Findings supporting recurrent infection, overt circulatory failure, hypoxemia, or liver failure were lacking. Treatment with continuous hemodiafiltration, glucose administration, and sodium bicarbonate improved the lactate level and corrected acidosis, hyperkalemia, and hypoglycemia. Given the continuation of imeglimin despite the progression of AKI, increased imeglimin exposure due to renal deterioration may have contributed to the development of lactic acidosis and hypoglycemia. When acute changes in renal function occur, the continuation of renally excreted antidiabetic agents, including imeglimin, should be repeatedly reassessed throughout the clinical course.
