COMPOSITIONS AND METHODS FOR THE TREATMENT OF OPIOID OVERDOSE
Drug products adapted for nasal delivery, comprising a pre-primed device filled with a pharmaceutical composition comprising nalmefene are provided. Methods of treating opioid overdose with the drug products are also provided.
1 .- 71 . (canceled)
72 . A pharmaceutical formulation for intranasal administration, comprising:
a. between about 1% (w/v) to about 4% (w/v) nalmefene, or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
b. between about 0.1% (w/v) to about 2.5% (w/v) of an alkylsaccharide absorption enhancer selected from the group consisting of dodecyl maltoside, tetradecyl maltoside, octyl maltoside, decyl maltoside, nonyl maltoside, undecyl maltoside, tridecyl maltoside, pentadecyl maltoside, hexadecyl maltoside, heptadecyl maltoside, octadecyl-α-maltoside, and octadecyl-β-D-maltoside, dodecyl glucoside, tetradecyl glucoside, octyl glucoside, decyl glucoside, nonyl glucoside, undecyl glucoside, tridecyl glucoside, pentadecyl glucoside, hexadecyl glucoside, heptadecyl glucoside, octadecyl-α-glucoside, and octadecyl-β-D-glucoside, dodecyl sucroside, tetradecyl sucroside, octyl sucroside, decyl sucroside, nonyl sucroside, undecyl sucroside, tridecyl sucroside, pentadecyl sucroside, hexadecyl sucroside, heptadecyl sucroside, octadecyl-α-sucroside, octadecyl-β-D-sucroside, and combinations thereof;
c. between about 0.2% (w/v) to about 1.2% (w/v) of sodium chloride;
d. between about 0.005% (w/v) to about 1% (w/v) of a preservative;
e. between about 0.1% (w/v) to about 0.5% (w/v) of disodium edetate; and
f. water in an amount sufficient to achieve a final volume of about 50 to about 250 microliters.
73 . The pharmaceutical formulation of claim 72 , comprising about 3% (w/v) of nalmefene hydrochloride.
74 . The pharmaceutical formulation of claim 72 , comprising about 2.7% (w/v) of nalmefene free base.
75 . The pharmaceutical formulation of claim 72 , comprising about 0.25% (w/v) of dodecyl maltoside.
76 . The pharmaceutical formulation of claim 72 , wherein the preservative is benzalkonium chloride.
77 . The pharmaceutical formulation of claim 76 , comprising about 0.04% (w/v) of benzalkonium chloride.
78 . The pharmaceutical formulation of claim 72 , comprising about 0.87% (w/v) of sodium chloride.
79 . The pharmaceutical formulation of claim 72 , comprising about 0.2% (w/v) of disodium edetate.
80 . The pharmaceutical formulation of claim 72 , further comprising an acid.
81 . The pharmaceutical formulation of claim 80 , wherein the acid is hydrochloric acid.
82 . The pharmaceutical formulation of claim 72 , wherein the pH of the formulation is between about 3.5 to about 5.5.
83 . The pharmaceutical formulation of claim 72 , wherein between about 50 to 250 microliters of the formulation is administered to a human subject to treat opioid overdose or a symptom thereof.
84 . The pharmaceutical formulation of claim 83 , wherein the symptom is selected from the group consisting of respiratory depression, central nervous system depression, altered level consciousness, miotic pupils, cardiovascular depression, hypoxemia, acute lung injury, aspiration pneumonia, sedation, unresponsiveness to stimulus, unconsciousness, stopped breathing, erratic or stopped pulse, choking or gurgling sounds, blue or purple fingernails or lips, slack or limp muscle tone, contracted pupils, vomiting, and hypotension.
85 . A pharmaceutical formulation for intranasal administration, comprising:
a. between about 1 mg to about 4 mg nalmefene, or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
b. between about 0.1 mg to about 2.5 mg of an alkylsaccharide absorption enhancer selected from the group consisting of dodecyl maltoside, tetradecyl maltoside, octyl maltoside, decyl maltoside, nonyl maltoside, undecyl maltoside, tridecyl maltoside, pentadecyl maltoside, hexadecyl maltoside, heptadecyl maltoside, octadecyl-α-maltoside, and octadecyl-β-D-maltoside, dodecyl glucoside, tetradecyl glucoside, octyl glucoside, decyl glucoside, nonyl glucoside, undecyl glucoside, tridecyl glucoside, pentadecyl glucoside, hexadecyl glucoside, heptadecyl glucoside, octadecyl-α-glucoside, and octadecyl-β-D-glucoside, dodecyl sucroside, tetradecyl sucroside, octyl sucroside, decyl sucroside, nonyl sucroside, undecyl sucroside, tridecyl sucroside, pentadecyl sucroside, hexadecyl sucroside, heptadecyl sucroside, octadecyl-α-sucroside, octadecyl-β-D-sucroside, and combinations thereof;
c. between about 0.2 mg to about 1.2 mg of sodium chloride;
d. between about 0.005 mg to about 1 mg of a preservative;
e. between about 0.1 mg to about 0.5 mg of disodium edetate; and
f. water in an amount sufficient to achieve a final volume of about 50 to about 250 microliters.
86 . The pharmaceutical formulation of claim 85 , comprising about 3 mg of nalmefene hydrochloride.
87 . The pharmaceutical formulation of claim 85 , comprising about 2.7 mg of nalmefene free base.
88 . The pharmaceutical formulation of claim 85 , comprising about 0.25 mg of dodecyl maltoside.
89 . The pharmaceutical formulation of claim 85 , wherein the preservative is benzalkonium chloride.
90 . The pharmaceutical formulation of claim 89 , comprising about 0.04 mg of benzalkonium chloride.
91 . The pharmaceutical formulation of claim 85 , comprising about 0.87 mg of sodium chloride.
92 . The pharmaceutical formulation of claim 85 , comprising about 0.2 mg of disodium edetate.
93 . The pharmaceutical formulation of claim 85 , further comprising an acid.
94 . The pharmaceutical formulation of claim 93 , wherein the acid is hydrochloric acid.
95 . The pharmaceutical formulation of claim 85 , wherein about 100 microliters of the formulation is administered to a human subject to treat opioid overdose or a symptom thereof.
96 . The pharmaceutical formulation of claim 95 , wherein opioid overdose is caused by a synthetic opioid.
97 . The pharmaceutical formulation of claim 95 , wherein the opioid overdose is caused by fentanyl or derivatives thereof.
98 . The pharmaceutical formulation of claim 85 , wherein the pharmaceutical formulation is administered by a single-use, pre-primed device adapted for nasal delivery of a pharmaceutical formulation to a subject.
99 . The pharmaceutical formulation of claim 98 , wherein the pharmaceutical formulation is delivered to the subject by one actuation of the device into one nostril of the subject.
100 . The pharmaceutical formulation of claim 85 , wherein the pharmaceutical formulation is administered by a pre-primed, bi-dose device adapted for nasal delivery of a pharmaceutical formulation to a subject, wherein a first volume of the pharmaceutical formulation is present in a first reservoir, and a second volume of the pharmaceutical formulation is present in a second reservoir, and wherein the therapeutically effective amount of the nalmefene is delivered essentially by a first actuation of the drug delivery device from the first reservoir into a nostril of the subject and a second actuation of the drug delivery device from the second reservoir into a nostril of the subject.