Efficacy and Safety of a Novel ĸ-Agonist for Managing Intractable Pruritus in Dialysis Patients

Abstract

Background: Our previous placebo-controlled, prospective, double-blind study demonstrated that a new opioid ĸ-receptor agonist, nalfurafine hydrochloride, effectively reduced treatment-resistant pruritus in 337 hemodialysis patients. Thus, we designed this study to evaluate prospectively the efficacy, safety, addiction liability, and pharmacokinetics of nalfurafine given orally for 1 year. Methods: This open-label study examined the effects and adverse drug reactions (ADRs) of 52-week oral administration of nalfurafine hydrochloride (5 µg/day) in 211 hemodialysis patients with a treatment-resistant itch. Results: Of 211 patients, 145 completed the study as scheduled. The mean pruritus value assessed by the visual analogue scale was 75.2 mm during the pre-observation period, which decreased significantly to 50.9 and 30.9 mm in week 2 and 52, respectively, indicating a long-lasting efficacy. ADRs occurred in 103 patients (48.8%). Frequent ADRs were insomnia (sleep disturbance, 19.4%), constipation (7.1%) and increased blood prolactin (3.3%), similar to previous reports. Regarding addiction liability, it appeared unlikely that nalfurafine hydrochloride was abused. After the start of treatment, plasma drug levels reached a steady state in week 2 with no apparent tendency of systemic accumulation. Conclusions: Nalfurafine hydrochloride, orally administered at 5 µg/day for 52 weeks to hemodialysis patients, produced a long-term suppression of pruritus without significant safety problems.

Post-marketing surveillance study of the safety and efficacy of nalfurafine hydrochloride (Remitch^®capsules 2.5 μg) in 3,762 hemodialysis patients with intractable pruritus

“…26 Nalfurafine was also demonstrated to be clinically effective in an open-label trial when administered at 5.0 μg/day for 1 year to 211 hemodialysis patients with intractable pruritus resistant to existing treatment. 27 The latter long-term study found no psychological or physical dependence on nalfurafine.…”

“…27,31 For each period, dependence during nalfurafine treatment was measured by 10 questions. Additionally, in case treatment was interrupted during each observation period, dependence during the 4 weeks after the end of treatment was assessed by six questions.…”

Опиоидные Κ-Рецепторы Как Молекулярная Мишень Для Создания Нового Поколения Обезболивающих Лекарственных Средств

“…10) -àãîíèñò k 2 -è k 3 -îïèîèä-íûõ ðåöåïòîðîâ èìååò ôàðìàêîëîãè÷åñêèé ïðîôèëü, îòëè÷íûé îò òàêîâîãî êëàññè÷åñêèõ U50,488 è U69,593 [100,101]. Áûëè èçó÷åíû ïðîòèâîçóäíûå ýô-ôåêòû TRK-820 [102,103].…”

“… óñëîâèÿõ TRK-820-îïîñðåäîâàííîé ñóïðàñïèíàëüíîé àíàëüãåçèè îòíîøå-íèå ïîêàçàòåëåé ÝÄ 50 ñåäàöèè/ÝÄ 50 àíòèíîöèöåïöèè îêàçàëîñü ñóùåñòâåííî âûøå ïî ñðàâíåíèþ ñ òàêîâû-ìè äëÿ U-50,488 è ICI-199,441 [104]. Êðîìå òîãî, íàë-ôóðàôèí íå âûçûâàë ïñèõîòîìèìåòè÷åñêèõ ýôôåêòîâ ó çäîðîâûõ äîáðîâîëüöåâ [101,105], à òàêaeå ýôôåêòîâ ïîäêðåïëåíèÿ èëè àâåðñèâíûõ ðàññòðîéñòâ â äîçàõ äî 80 ìêã/êã [42]. Ñ 2009 ã. íàëôóðàôèí (òîðãîâîå íàçâà-íèå "Remitch") ðàçðåøåí ê ïðèìåíåíèþ íà òåððèòîðèè ßïîíèè â êà÷åñòâå ëåêàðñòâåííîãî ïðåïàðàòà äëÿ ëå÷å-íèÿ óðåìè÷åñêîãî çóäà ó áîëüíûõ, íàõîäÿùèõñÿ íà ãå-ìîäèàëèçå, ðåçèñòåíòíûõ ê ñòàíäàðòíîé òåðàïèè [101,103,106,107].…”

“…Êðîìå òîãî, íàë-ôóðàôèí íå âûçûâàë ïñèõîòîìèìåòè÷åñêèõ ýôôåêòîâ ó çäîðîâûõ äîáðîâîëüöåâ [101,105], à òàêaeå ýôôåêòîâ ïîäêðåïëåíèÿ èëè àâåðñèâíûõ ðàññòðîéñòâ â äîçàõ äî 80 ìêã/êã [42]. Ñ 2009 ã. íàëôóðàôèí (òîðãîâîå íàçâà-íèå "Remitch") ðàçðåøåí ê ïðèìåíåíèþ íà òåððèòîðèè ßïîíèè â êà÷åñòâå ëåêàðñòâåííîãî ïðåïàðàòà äëÿ ëå÷å-íèÿ óðåìè÷åñêîãî çóäà ó áîëüíûõ, íàõîäÿùèõñÿ íà ãå-ìîäèàëèçå, ðåçèñòåíòíûõ ê ñòàíäàðòíîé òåðàïèè [101,103,106,107].  íàñòîÿùåå âðåìÿ â Åâðîïå TRK-820 ïðîõîäèò êëèíè÷åñêèå èñïûòàíèÿ äëÿ ëå÷åíèÿ òÿaeå-ëîãî è õðîíè÷åñêîãî çóäà ïðè öèððîçå ïå÷åíè, àòîïè-÷åñêîì äåðìàòèòå, ýêçåìå, ïñîðèàçå, íåâðîëîãè÷åñêèõ ðàññòðîéñòâàõ, ýíäîêðèííîé ïàòîëîãèè, à òàêaeå ïðè ëå÷åíèè îíêîëîãè÷åñêèõ çàáîëåâàíèé è èíôåêöèé [47,108].…”