Comparison of nimodipine formulations and administration techniques via enteral feeding tubes in patients with aneurysmal subarachnoid hemorrhage: A multicenter retrospective cohort study

Abstract

Background: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH.

Nimodipine systemic exposure and outcomes following aneurysmal subarachnoid hemorrhage: a pilot prospective observational study (ASH-1 study)

“…We previously reported an association between the nimodipine administration technique and patient outcomes where patients receiving crushed nimodipine tablets enterally had worse outcomes compared to those who received whole tablets after controlling for disease severity (57). We confirmed such findings in a multicenter retrospective study where we compared various enteral administration formulations and techniques (22). This could be attributed to the reduced oral bioavailability of enteral nimodipine, especially the manufacturer recommends against tablet crushing due to the risk of reduced absorption (58).…”

“…All of the comparisons were not statistically different, except for (−)-R and total nimodipine among the participants who presented with high grades. (+)-R nimodipine AUC 0-3h in those who did not develop vasospasm were 4-fold significantly higher than those who had vasospasm [83(64-138) vs. 23 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) ng.h/mL, respectively, value of p = 0.047]. Similarly, (−)-R nimodipine C max in those who did not develop vasospasm were 4-fold significantly higher than those who had vasospasm [34(24-83) vs. 9 (6)(7)(8)(9)(10)(11) ng/mL, respectively, value of p = 0.009].…”

“…Pharmacokinetic studies have reported extensive variability of nimodipine concentrations in various populations and in the setting of aSAH, with some patients having undetectable nimodipine plasma levels (12)(13)(14)(15)(16)(17). The observed variability in nimodipine exposure may have been attributed to practice variations in nimodipine administration, systemic inflammation, disease severity, administration of concomitant interacting drugs, and cytochrome P450 polymorphism (17)(18)(19)(20)(21)(22). While previous randomized controlled trials have found that nimodipine reduces the incidence of poor neurologic outcomes (defined by death, persistent vegetative state, and severe disability) by 40-86%, a significant proportion of patients in the nimodipine arm experienced poor outcomes (10,23,24).…”

Implementing In-House Compounding of Nimodipine Oral Syringes for Aneurysmal Subarachnoid Hemorrhage Patients

“…Dear Editor, We are writing in response to a recent article published by Mahmoud et al, which found that enteral nimodipine formulations are not equivalent across multiple endpoints, such as the incidence of diarrhea and need for dosage reduction. 1 We would like to share our experience of successfully implementing in-house compounding of nimodipine oral syringes, given the favorability found in the endpoints studied and associated cost savings.…”