Dantrolene reconstitution

Giraldo-Gutiérrez, D.S.; Arrendo-Verbel, Marco Andrés; Rincón-Valenzuela, David A.

doi:10.1097/cj9.0000000000000028

Cited by 5 publications

(4 citation statements)

References 10 publications

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“…Although the time-saving benefit appears greater for children than adults, weight-based dosing means further time savings are likely in the adult population. This may reduce the morbidity and mortality associated with treatment delay, and reduce healthcare resource utilisation for a malignant hyperthermia event, including the clinical staff numbers needed, which could be beneficial at times of low staffing 4–7,15 . Savings in consumables such as syringes, needles and filtration devices are expected.…”

Section: Discussionmentioning

confidence: 99%

“…6 Dantrium1 is supplied in vials containing 20 mg dantrolene for reconstitution in 60 ml water by vigorous shaking; because of the poor solubility of dantrolene, preparation of a single vial can take more than 4 min. 7,8 For a 60 kg patient, effective doses may require 8 to greater than 30 vials, requiring the effort of at least three clinical staff and potentially contributing to critical delays. [6][7][8] To shorten the preparation and administration time and facilitate rapid interventions in emergency situations, a novel intravenous formulation of dantrolene, NPJ5008, has been developed using different excipients [2-hydroxypropyl-beta-cyclodextrin (HP-b-CD) and polyethylene glycol (PEG)].…”

Section: Introductionmentioning

confidence: 99%

“…7,8 For a 60 kg patient, effective doses may require 8 to greater than 30 vials, requiring the effort of at least three clinical staff and potentially contributing to critical delays. [6][7][8] To shorten the preparation and administration time and facilitate rapid interventions in emergency situations, a novel intravenous formulation of dantrolene, NPJ5008, has been developed using different excipients [2-hydroxypropyl-beta-cyclodextrin (HP-b-CD) and polyethylene glycol (PEG)]. With NPJ5008, the same dose of dantrolene can be reconstituted more rapidly and in smaller volumes than with Dantrium1 (unpublished observations).…”

Section: Introductionmentioning

confidence: 99%

“…These guidelines advise precautionary dantrolene stocking based on the DANTRIUM® IV (also marketed as DANTROLEN IV; Norgine, Harefield, UK) formulation available in Europe 6 . Dantrium® is supplied in vials containing 20 mg dantrolene for reconstitution in 60 ml water by vigorous shaking; because of the poor solubility of dantrolene, preparation of a single vial can take more than 4 min 7,8 . For a 60 kg patient, effective doses may require 8 to greater than 30 vials, requiring the effort of at least three clinical staff and potentially contributing to critical delays 6–8 .…”

Section: Introductionmentioning

confidence: 99%

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The novel rapid formulation of intravenous dantrolene (NPJ5008) versus standard dantrolene (Dantrium®)

Ng Kwet Shing,

Clayton,

Smith

et al. 2024

European Journal of Anaesthesiology

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BACKGROUND Delays in treating anaesthesia-induced malignant hyperthermia increase risks of complications and death. NPJ5008 is a novel formulation of the indicated treatment, dantrolene sodium, developed to shorten preparation and administration times compared with the reference formulation DANTRIUM IV. The two formulations have been compared preclinically. OBJECTIVES Assess bioequivalence of overall dantrolene (free acid) exposure of NPJ5008 versus DANTRIUM IV and ascertain similarities in their pharmacokinetics and safety/tolerability profiles. Evaluate preparation/administration time savings for the new formulation. DESIGN Part 1 of this open-label trial in humans was a 1 : 1 randomised crossover study; part 2 was a single-arm study. Trial pharmacy data and laboratory simulations assessed preparation/administration step timings. SETTING Single clinical centre in the UK, April to July 2021. PARTICIPANTS Twenty-one healthy male and female individuals. INTERVENTIONS Part 1: single intravenous 60 mg dose of NPJ5008 or DANTRIUM IV, sequentially. Part 2: single intravenous 120 mg dose of NPJ5008. Simulation: five vials per formulation using paediatric and adult cannulas. MAIN OUTCOME MEASURES Overall drug exposure to last measurable concentration (AUC0 to last) and extrapolated to infinity (AUC0 to ∞) were primary endpoints. Other pharmacokinetic, clinical and muscle-function parameters, and adverse events, were monitored. RESULTS Adjusted geometric mean ratios of NPJ5008 versus DANTRIUM IV were 90.24 and 90.44% for AUC0 to last and AUC0 to ∞, respectively, with the 90% confidence intervals (CI) within the 80 to 125% acceptance interval, establishing bioequivalence. No new safety issues emerged: any adverse events were of a similar magnitude across treatments and related to pharmacological properties of dantrolene. Pharmacy and simulation data revealed that every step in preparation and administration was 26 to 69% faster for NPJ5008 than DANTRIUM IV. CONCLUSION NPJ5008 showed comparable pharmacokinetic and safety profiles to DANTRIUM IV, while reducing dantrolene dose preparation/administration times, potentially reducing patient complications/healthcare resourcing in malignant hyperthermia. TRIAL REGISTRATION EudraCT Number: 2020-005719-35, MHRA approval.

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Section: Discussionmentioning

confidence: 99%