Nefopam Pharmacokinetics in Patients with End-Stage Renal Disease

Abstract

Nefopam distribution and elimination are altered in patients with ESRD, resulting in heightened exposure. To avoid too-high concentration peaks, it is suggested that the daily nefopam dose be reduced by 50%.

Nefopam as an adjunct to intravenous patient‐controlled analgesia after renal transplantation: a randomised trial

“…16 Although the recommended maximal daily nefopam dose is 120 mg for healthy subjects, pharmacokinetic study in end-stage renal disease patients suggests that the daily nefopam dose should be reduced by 50% because of altered distribution and elimination. 18 Endstage renal disease influences hepatic metabolism, particularly by cytochrome P450 through toxins such as urea, cytokines, and parathyroid hormone. 19,20 However, this inhibitory effect of uremic toxins on cytochrome P450 may disappear after successful renal transplantation.…”

“…In addition, continuous infusion of nefopam may allow for a safety margin at a higher dosage in renal recipients based on pharmacokinetic simulation of different regimens in end-stage renal disease patients, in which peak plasma concentration of nefopam was lower with the 10 mg every 4 h regimen than with the 20 mg every 8 h regimen. 18 The merit of multimodal analgesia is not only improvement in analgesia but also limited opioidrelated side effects. 5 In a previous study, nefopam provided a morphine-sparing effect with less nausea or vomiting after hepatic resection.…”

“…11,14 In the current study, the absence of tachycardia may be related to continuous infusion of nefopam associated with lower peak plasma concentration than that of IV injection of nefopam. 15,18 Two patients in the nefopam group experienced transient confusion/hallucination after 12 h of nefopam infusion; they had normal creatinine level within 2 days after renal transplantation and no operation-related complications. In addition, the use of nefopam did not exert a negative influence on early graft function, delayed graft function, and acute rejection episodes.…”

“…16,17 Therefore, in contrast to NSAIDs, nefopam can be safely used as an analgesic adjuvant with opioid-based IV PCA in patients with impaired renal function. Although distribution and elimination of nefopam are altered in patients with end-stage renal disease, 18 this decreased metabolic clearance seems to recover after renal transplantation mainly due to disappearance of uremic toxins. 19,20 Considering patient population-specific pain management strategy, the analgesic efficacy and safety of nefopam after renal transplantation as a multimodal analgesic adjunct have not been addressed.…”

Comment utiliser les antalgiques non opiacés en postopératoire ?

“…Des cas de cécité ont été rapportés [15]. En cas d'insuffisance rénale terminale (clairance de la créatinine < 20 mL/ min), les posologies doivent être réduites de 50 % [16]. Enfin, le néfopam aurait des propriétés anti-hyperalgésiques qui ont été mises en évidence dans des études animales.…”