US 12,290,596 B2
Compositions and methods for the treatment of opioid overdose
Phil Skolnick, Santa Monica, CA (US); Mark Ellison, Santa Monica, CA (US); and Roger Crystal, Santa Monica, CA (US)
Assigned to Indivior UK Limited, Hull (GB)
Filed by INDIVIOR INC., North Chesterfield, VA (US)
Filed on Aug. 4, 2022, as Appl. No. 17/881,306.
Claims priority of provisional application 63/229,300, filed on Aug. 4, 2021.
Prior Publication US 2023/0055547 A1, Feb. 23, 2023
Int. Cl. A61K 9/00 (2006.01); A61K 31/485 (2006.01); A61K 47/18 (2017.01); A61K 47/26 (2006.01); A61P 25/36 (2006.01)
CPC A61K 9/0043 (2013.01) [A61K 31/485 (2013.01); A61K 47/183 (2013.01); A61K 47/186 (2013.01); A61K 47/26 (2013.01); A61P 25/36 (2018.01)] 2 Claims
OG exemplary drawing
 
1. A method of emergency treatment of a known or suspected opioid overdose or a symptom thereof caused by natural or synthetic opioids in an adult human subject in need thereof, comprising nasally administering to the subject a pharmaceutical formulation in an aqueous solution of about 100 μL, comprising:
about 3 mg of nalmefene hydrochloride;
about 0.87 mg NaCl;
about 0.25 mg dodecyl maltoside;
about 0.04 mg benzalkonium chloride (50% solution);
about 0.2 mg disodium edetate; and
water in an amount sufficient to achieve a volume of about 100 μL;
wherein said formulation has a pH of 4.1 to 4.9;
further wherein upon intranasal administration of said formulation to said adult human subject, median Tmax is less and the Cmax geometric mean is higher than each would have been for intramuscular administration of 1 mg nalmefene hydrochloride;
further wherein upon intranasal administration of said formulation to said adult human subject, the time to onset of reversal in said adult human subject of a remifentanil-induced respiratory depression ranges from 2.5 to 5 minutes after said administration in a ventilatory-response to hypercapnia model, and the time to full reversal of remifentanil-induced depression of minute ventilation in said adult human subject ranges from 5 and 15 minutes after said administration in the model;
further wherein the plasma concentration versus time curve of the nalmefene in said adult human subject has a Tmax of between 12 and 18 minutes; and wherein the Cmax geometric mean is between 89 ng/ml and 12 ng/ml;
thereby treating the opioid overdose or a symptom thereof in the adult human subject.