ESKETAMINE FOR THE TREATMENT OF DEPRESSION
The present invention provides methods for treating depression in a patient, comprising administering to the patient in need of the treatment a therapeutically effective amount of esketamine. In some embodiments, the depression is major depressive disorder or treatment resistant depression. In other embodiments, the therapeutically effective amount is clinically proven safe and/or effective. Also provided are methods to mitigate the risk or misuse or abuse of esketamine, instructions for use of the esketamine product, and methods for selling a drug product containing esketamine.
1 - 23 . (canceled)
24 . A method of selling an approved drug product comprising esketamine, said method comprising selling such drug product, wherein a drug product label for a reference listed drug for such drug product includes instructions for treating depression.
25 . A method of offering for sale an approved drug product comprising esketamine, said method comprising offering for sale such drug product, wherein a drug product label for a reference listed drug for such drug product includes instructions for treating depression.
26 . The method of claim 24 , wherein the drug product is an ANDA drug product, a supplemental New Drug Application drug product, or a 505(b)(2) drug product.
27 . The method of claim 24 , wherein the depression is major depressive disorder.
28 . The method of claim 24 , wherein the drug product label includes instructions to co-administer the esketamine with an oral antidepressant.
29 . The method of claim 24 , wherein the drug product label comprises data directed to improving depressive symptoms relative to a placebo.
30 .- 34 . (canceled)
35 . The method of claim 24 , wherein administration of the esketamine to a patient achieves a maximum plasma concentration (C max ) of 45 to about 165 ng/mL and an area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC last ) of about 125 to about 490 ng*h/mL, or a combination thereof.
36 . The method of claim 35 , wherein the approved drug product comprises about 28 mg of esketamine and wherein administration of the esketamine to a patient achieves a maximum plasma concentration (C max ) of esketamine of about 45 to about 75 ng/mL, an area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC last ) of about 125 to about 185 ng*h/mL, or a combination thereof.
37 . The method of claim 35 , wherein the approved drug product comprises about 56 mg of esketamine and wherein administration of the esketamine to a patient achieves a maximum plasma concentration (C max ) of esketamine of about 65 to about 120 ng/mL, an area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC last ) of about 210 to about 320 ng*h/mL, or a combination thereof.
38 . The method of claim 35 , wherein the approved drug product comprises about 84 mg of esketamine and wherein administration of the esketamine to a patient achieves a maximum plasma concentration (C max ) of about 90 to about 165 ng/mL, an area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC last ) of about 305 to about 490 ng*h/mL, or a combination thereof.
39 . (canceled)
40 . The method of claim 24 , wherein the approved product comprises one or more intranasal spray devices, the one or more devices comprise the esketamine, and the one or more devices is configured to administer from about 28 to about 84 mg of esketamine.
41 . The method of claim 40 , wherein the one or more devices is configured to administer the esketamine in two or more sprays.
42 . The method of claim 40 , wherein the one or more devices comprise about 28 mg of esketamine.
43 . The method of claim 40 , wherein each of the one or more devices comprise about 28 mg of esketamine.
44 . The method of claim 40 , wherein each of the one or more devices is a single use device.
45 . The method of claim 40 , wherein the approved drug product comprises three devices.
46 . The method of claim 40 , further comprising administering the esketamine to a patient.
47 . The method of claim 46 , wherein the esketamine is administered to a patient that is supervised by a healthcare professional.
48 . The method of claim 47 , wherein the esketamine is administered in two sprays of a single device.
49 . The method of claim 48 , wherein one spray is administered to each nostril of a patient.
50 . The method of claim 49 , wherein the single device is discarded following the second spray.
51 . The method of claim 50 , wherein about 5 minutes elapses between the use of any two of the one or more devices.
52 . The method of claim 24 , wherein the drug product label includes instructions to mitigate risk of misuse or abuse of esketamine, comprising restricting distribution of the approved drug product to selected distributors, wherein the distributors are Drug Enforcement Administration registered and deliver the approved drug product only to a pre-approved site of care.
53 . The method of claim 52 , wherein the pre-approved site of care is a hospital, mental health clinic, physician office, or outpatient pharmacy.
54 . The method of claim 52 , wherein the site of care is certified under a Risk Evaluation Mitigation Strategy (REMS) for esketamine that has been approved by the Food and Drug Administration.
55 . The method of claim 54 , wherein the REMS requires esketamine to be self-administered by a patient under the supervision of a healthcare professional.
56 . The method of claim 52 , wherein the approved esketamine drug product comprises a nasal spray device.
57 . The method of claim 56 , wherein the nasal spray device is a single-use, disposable device that delivers 28 mg of esketamine in only two sprays with minimal residual esketamine remaining after the second spray.
58 . The method of claim 57 , wherein the minimal residual remaining esketamine is less than about 4 mg.
59 . The method of claim 24 , wherein the drug product label warns against concomitant use of any one of a central nervous system depressant, a psychostimulant, and a monoamine oxidase inhibitor.