Non-sedating dexmedetomidine treatment regimens
Disclosed herein are methods of administering relatively high doses of dexmedetomidine or a pharmaceutically acceptable salt thereof to a human subject, without also inducing significant sedation. The disclosed methods are particularly suitable for the treatment of agitation, especially when associated with neurodegenerative and/or neuropsychiatric diseases such as schizophrenia, bipolar illness such as bipolar disorder or mania, dementia, depression, or delirium.
1. A method of treating an agitation of a human subject in need thereof using an oromucosal formulation of dexmedetomidine or a pharmaceutically acceptable salt thereof, the method comprising:
administering a first dose of the oromucosal formulation of dexmedetomidine or a pharmaceutically acceptable salt thereof to the human subject, wherein the first dose is 60 mcg, 80 mcg, 90 mcg, 120 mcg, or 180 mcg of dexmedetomidine;
and, after at least two hours,
administering a second dose of the oromucosal formulation of dexmedetomidine or a pharmaceutically acceptable salt thereof to the human subject, and wherein the second dose is 40 mcg, 60 mcg, 80 mcg, 90 mcg, or 120 mcg of dexmedetomidine; and
wherein the human subject has a corrected QT interval using Fridericia's correction method (QTcF) of no greater than 450 msec for males and no greater than 470 msec for females.
2. The method of claim 1 , wherein the initial dose is 60 mcg or 120 mcg.
3. The method of claim 1 , wherein the second dose is 60 mcg or 120 mcg.
4. The method of claim 1 , wherein the agitation is associated schizophrenia or bipolar disorders.
5. The method of claim 4 , wherein the first dose is 120 mcg and the second dose is 120 mcg.
6. The method of claim 5 , wherein the second dose is administered at least 4 hours after the first dose.
7. The method of claim 6 , wherein the second dose is administered at least 6 hours after the first dose.
8. The method of claim 6 , wherein the second dose is administered at least 8 hours after the first dose.
9. The method of claim 6 , wherein the second dose is administered at least 10 hours after the first dose.
10. The method of claim 6 , wherein the second dose is administered at least 12 hours after the first dose.
11. The method of claim 6 , wherein the second dose is administered at least 14 hours after the first dose.
12. The method of claim 6 , wherein the second dose is administered at least 16 hours after the first dose.
13. The method of claim 6 , wherein the second dose is administered at least 18 hours after the first dose.
14. The method of claim 6 , wherein the second dose is administered at least 20 hours after the first dose.
15. The method of claim 1 , wherein the agitation is associated dementia.
16. The method of claim 15 , wherein the first dose is 60 mcg and the second dose is 60 mcg.
17. The method of claim 16 , wherein the second dose is administered at least 4 hours after the first dose.
18. The method of claim 17 , wherein the second dose is administered at least 6 hours after the first dose.
19. The method of claim 17 , wherein the second dose is administered at least 8 hours after the first dose.
20. The method of claim 17 , wherein the second dose is administered at least 10 hours after the first dose.
21. The method of claim 17 , wherein the second dose is administered at least 12 hours after the first dose.
22. The method of claim 17 , wherein the second dose is administered at least 14 hours after the first dose.
23. The method of claim 17 , wherein the second dose is administered at least 16 hours after the first dose.
24. The method of claim 17 , wherein the second dose is administered at least 18 hours after the first dose.
25. The method of claim 17 , wherein the second dose is administered at least 20 hours after the first dose.