Combinations and methods
The present disclosure relates to novel methods of treating pain comprising administering to a human in need thereof an effective amount of (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, substantially free of the corresponding (−) enantiomer, wherein the human is a heavy drinker and/or binge drinker and/or wherein the human has compromised liver function and/or wherein the human is a codeine non-responder. The present disclosure also relates to a method of treating pain comprising concurrently or sequentially administering to a patient in need thereof an effective amount of (a) (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, and (b) acetaminophen. The present disclosure also relates to a method of treating pain comprising simultaneously or sequentially administering to a patient in need thereof an effective amount of (a) (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, and (b) a non-steroidal anti-inflammatory drug.
1. A method of treating pain comprising administering to a human in need thereof an effective amount of (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, substantially free of the corresponding (−) enantiomer, wherein the human is a heavy drinker.
2. A method of treating pain comprising administering to a patient in need thereof an effective amount of (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, substantially free of the corresponding (−) enantiomer, wherein the patient has compromised liver function.
3. The method according to claim 1 , wherein the effective amount of (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, comprises less than or equal to 2% w/w of the corresponding (−) enantiomer.
4. The method according to claim 1 , wherein the effective amount of (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, comprises less than or equal to 1% w/w of the corresponding (−) enantiomer.
5. The method according to claim 1 , wherein the (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane is in pharmaceutically acceptable salt form.
6. The method according to claim 1 , wherein the (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane in pharmaceutically acceptable salt form is (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane hydrochloride.
7. The method according to claim 1 , wherein the (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, is Polymorph A substantially free of other polymorphic forms.
8. The method according claim 1 , wherein the pain is chronic pain.
9. The method according to claim 1 , wherein the pain is neuropathic pain.
10. The method according to claim 1 further comprising administering a second therapeutic agent.
11. A method of treating pain comprising concurrently or sequentially administering to a patient in need thereof an effective amount of: (a) (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, and (b) acetaminophen.
12. A method of treating pain comprising concurrently or sequentially administering to a patient in need thereof an effective amount of: (a) (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, and (b) a non-steroidal anti-inflammatory drug.
13. The method according to claim 11 , wherein the effective amount of (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, comprises less than or equal to 2% w/w of the corresponding (−) enantiomer.
14. The method according to claim 11 , wherein the effective amount of (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, comprises less than or equal to 1% w/w of the corresponding (−) enantiomer.
15. The method according to claim 11 , wherein the (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane is in pharmaceutically acceptable salt form.
16. The method according to claim 11 , wherein the (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane in pharmaceutically acceptable salt form is (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane hydrochloride.
17. The method according to claim 11 , wherein the (1R,5S)-(+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, in free and/or pharmaceutically acceptable salt form, is Polymorph A substantially free of other polymorphic forms.
18. The method according to claim 11 , wherein the pain is chronic pain.
19. The method according to claim 11 , wherein the pain is neuropathic pain.
20. The method according to claim 11 , wherein the patient is a heavy drinker.
21. The method according to claim 11 , wherein the patient is a binge drinker.
22. The method according to claim 11 , wherein the patient has compromised liver function.
23. The method according to claim 11 , wherein the patient is a codeine non-responder.