er birth. When patency is small, it is generally asymptomatic, but when the patency is large and the symptoms worsen, severe complications such as intracranial hemorrhage, necrotizing enterocolitis, pulmonary hemorrhage and renal failure (oliguria) It is suggested that it may also affect long-term prognosis such as chronic lung disease, retinopathy of prematurity, and malnutrition.
Medical therapy or surgical therapy is performed after conservative therapy such as moisture restriction or diuretic drug administration is performed as a treatment for patent ductus arteriosa in premature infants, but before surgical therapy, medical therapy Pharmacological ligation therapy with prostaglandin (PG) synthesis inhibitor has been performed as a drug. In Japan, only the intravenous formulation of indomethacin sodium (indacin) was the only PG inhibitor with PDA indication. Although this indomethacin preparation has high effectiveness, side effects such as anuria, oliguria and renal dysfunction have been a problem to be solved.
Ibuprofen L-lysine preparation is the second drug as a PG synthesis inhibitor, and it has already been clinically used for PDA in Europe and the United States. In addition, ibuprofen preparations are reported to be more safe than indomethacin preparations. Based on this, a request for early approval from the Japan Premature Infant Conference on Neonatal Society (present: Japan Society of Neonatal Development and Medicine) was submitted in 2012, and "Request for early approval was submitted," Unconfirmed drug / (Held in September, Heisei 20), the development has progressed and this approval has been reached.
On the basis of nonclinical study results and clinical test results in the United States, the domestic phase III trial for PDA patients in Japan confirmed the same effectiveness as indomethacin preparation.
In the domestic phase III trial, side effects (including abnormal laboratory test values) are recognized in 85.0%. The main one is urine volume reduction (including oliguria) (40.0%), renal dysfunction (25.0%), increase in blood creatine (20.0%), increase in blood urea (15.0%), the serious one Acute kidney injury, anuria, pulmonary hypertension, necrotizing enterocolitis, digestive tract perforation, ileus, thrombocytopenia, bleeding, gastrointestinal bleeding, pulmonary hemorrhage, intracranial hemorrhage have been reported.
Since ibuprofen L-lysine preparation is extremely limited in domestic clinical cases, it is necessary to conduct a usage record survey for all cases until data on a certain number of cases are accumulated after manufacturing and sales In addition to grasping the background information of patients using this drug, we will collect data on the safety and efficacy of this drug at an early stage and take necessary measures to properly use this drug.
