Compositions and methods for the treatment of opioid overdose
View Patent ↗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. A pharmaceutical formulation for intranasal administration, comprising:
about 3% (w/v) nalmefene hydrochloride;
between about 0.1% (w/v) and about 0.5% (w/v) dodecyl maltoside; between about 0.2% (w/v) and about 1.2% (w/v) NaCl
between about 0.13% (w/v) and about 0.67% (w/v) disodium edetate;
between about 0.001% (w/v) and about 0.1% (w/v) benzalkonium chloride;
an amount of an acid or base sufficient to achieve a pH of between 3.5 and 5.5; and
water in an amount sufficient to achieve a final volume of about 50 μL to about 200 μL.
2. A pharmaceutical formulation for intranasal administration, comprising: about 3 mg nalmefene hydrochloride or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
between about 0.1 mg and about 0.5 mg dodecyl maltoside;
between about 0.2 mg and about 1.2 mg NaCl;
between about 0.13 mg and about 0.67 mg disodium edetate;
between about 0.001 mg and about 0.1 mg benzalkonium chloride;
an amount of an acid or base sufficient to achieve a pH of between 3.5 and 5.5; and
water in an amount sufficient to achieve a final volume of about 100 μL.
3. The pharmaceutical formulation as recited in claim 1 , comprising about 0.25% (w/v) dodecyl maltoside.
4. A device adapted for nasal delivery of a pharmaceutical formulation to a patient by actuation of the device into a nostril of the patient, the device comprising a pharmaceutical formulation as recited in claim 1 .
5. A method of treating opioid overdose for at least 3 hours in a patient in need thereof, comprising nasally administering to the patient, a pharmaceutical formulation as recited in claim 1 , thereby treating opioid overdose in the patient.
6. The pharmaceutical formulation as recited in claim 2 , comprising about 3 mg nalmefene hydrochloride or a hydrate thereof.
7. The pharmaceutical formulation as recited in claim 2 , wherein upon the administration to a human subject of about 3 mg of nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof, the T max is 20 minutes or less.
8. The pharmaceutical formulation as recited in claim 2 , wherein upon the administration to a human subject of about 3 mg of nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof, the T max is 15 minutes or less.
9. The pharmaceutical formulation as recited in claim 2 , wherein upon the administration to a human subject of about 3 mg of nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof, the T max after administration of the composition is lower than the Tmax of an intranasal formulation of about 3 mg nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof that does not contain dodecyl maltoside.
10. The pharmaceutical formulation as recited in claim 2 , wherein upon the administration to a human subject of about 3 mg of nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof, the Tmax after administration of the composition is at least about 85% lower than the Tmax of an intranasal formulation of about 3 mg nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof that does not contain dodecyl maltoside.
11. The pharmaceutical formulation as recited in claim 2 , wherein upon administration to a human subject of about 3 mg of the nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof, the Tmax after administration of the composition is about 80% to about 90% lower than the Tmax of an intranasal formulation of about 3 mg nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof that does not contain dodecyl maltoside.
12. The pharmaceutical formulation as recited in claim 2 , wherein upon administration to a human subject of about 3 mg of the nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof, the Cmax after administration of the composition is at least about 2 times higher than the Cmax of an intranasal formulation of about 3 mg nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof that does not contain dodecyl maltoside.
13. The pharmaceutical formulation as recited in claim as recited in claim 2 , wherein upon the administration to a population of human subjects of about 3 mg of nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof, the mean concentration of nalmefene at about 5 minutes post-dose is about 1 ng/mL.
14. The pharmaceutical formulation as recited in claim as recited in claim 2 , wherein upon the administration to a population of human subjects of about 3 mg of nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof, the mean concentration of nalmefene at about 15 minutes post-dose is about 4 ng/mL.
15. The pharmaceutical formulation as recited in claim as recited in claim 2 , wherein upon the administration to a population of human subjects of about 3 mg of nalmefene or a pharmaceutically acceptable salt, hydrate, or solvate thereof, the mean concentration of nalmefene at about 30 minutes post-dose is about 3 ng/mL.