Details for Patent: 9,789,103

Title:	Method of treating pain utilizing controlled release oxymorphone pharmaceutical compositions and instruction on dosing for renal impairment
Abstract:	The invention pertains to a method of using oxymorphone in the treatment of pain by providing a patient with an oxymorphone dosage form and informing the patient or prescribing physician that the bioavailability of oxymorphone is increased in patients with renal impairment.
Inventor(s):	Ahdieh; Harry (Lincoln University, PA)
Assignee:	ENDO PHARMACEUTICALS INC. (Malvern, PA)
Filing Date:	Jul 21, 2014
Application Number:	14/336,753
Claims:	1. A method of treating pain in a renally impaired patient comprising administering a pharmaceutical composition comprising about 5 mg to about 80 mg of oxymorphone or a pharmaceutically acceptable salt thereof as the sole active ingredient and a controlled release matrix, wherein the renally impaired patient is administered a dose of oxymorphone or a pharmaceutically acceptable salt thereof that is less than the dose administered to a comparable patient without renal impairment, and wherein the log transformed AUC of oxymorphone is about 1.05 to about 2.45 times greater than the log transformed AUC of a healthy patient if the healthy patient were to be administered the same dose. 2. A method of treating pain in a renally impaired patient comprising administering a pharmaceutical composition comprising about 5 mg to about 80 mg of oxymorphone or a pharmaceutically acceptable salt thereof as the sole active ingredient and a controlled release matrix, wherein (a) the renally impaired patient is administered a dose of oxymorphone or a pharmaceutically acceptable salt thereof that is less than the dose administered to a comparable patient without renal impairment, (b) the creatinine clearance rate of the patient is determining it to be about 51 mL/min to about 80 mL/min, and (c) the renally impaired patient has mild renal impairment and the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 0.86 to about 1.84 when administered equal doses. 3. The method of claim 2, wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.26 when administered equal doses. 4. The method of claim 2, wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 0.94 to about 2.03 when administered equal doses. 5. The method of claim 4, wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.38 when administered equal doses. 6. The method of claim 5, wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.26 when administered equal doses. 7. The method of claim 1, wherein the renally impaired patient has moderate renal impairment and the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.07 to about 2.31 when administered equal doses. 8. The method of claim 7, wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.57 when administered equal doses. 9. The method of claim 7, wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.12 to about 2.43 when administered equal doses. 10. The method of claim 9, wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.65 when administered equal doses. 11. The method of claim 10, wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.57 when administered equal doses. 12. The method of claim 1, wherein the renally impaired patient has severe renal impairment and the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.13 to about 2.42 when administered equal doses. 13. The method of claim 12, wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.65 when administered equal doses. 14. The method of claim 12, wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.23 to about 2.65 when administered equal doses. 15. The method of claim 14, wherein the ratio of Cmax of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.80 when administered equal doses. 16. The method of claim 15, wherein the ratio of AUC of oxymorphone or pharmaceutically acceptable salt thereof in the renally impaired patient to the comparable patient without renal impairment is about 1.265 when administered equal doses. 17. The method of claim 2, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 nghr/mL. 18. The method of claim 2, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 nghr/mL. 19. The method of claim 2, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 nghr/mL. 20. The method of claim 3, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 nghr/mL. 21. The method of claim 3, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 nghr/mL. 22. The method of claim 3, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 nghr/mL. 23. The method of claim 6, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 nghr/mL. 24. The method of claim 6, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 nghr/mL. 25. The method of claim 6, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 nghr/mL. 26. The method of claim 7, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 nghr/mL. 27. The method of claim 7, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 nghr/mL. 28. The method of claim 7, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 nghr/mL. 29. The method of claim 8, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 nghr/mL. 30. The method of claim 8, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 nghr/mL. 31. The method of claim 8, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 nghr/mL. 32. The method of claim 11, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 nghr/mL. 33. The method of claim 11, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 nghr/mL. 34. The method of claim 11, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 nghr/mL. 35. The method of claim 12, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 nghr/mL. 36. The method of claim 12, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 nghr/mL. 37. The method of claim 12, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 nghr/mL. 38. The method of claim 13, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 nghr/mL. 39. The method of claim 13, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 nghr/mL. 40. The method of claim 13, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 nghr/mL. 41. The method of claim 16, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 21 nghr/mL. 42. The method of claim 16, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 20 nghr/mL. 43. The method of claim 16, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average AUC of oxymorphone over a 12-hour period is less than 19 nghr/mL. 44. The method of claim 4, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ngmL. 45. The method of claim 4, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL. 46. The method of claim 4, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL. 47. The method of claim 5, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ng/mL. 48. The method of claim 5, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL. 49. The method of claim 5, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL. 50. The method of claim 9, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ng/mL. 51. The method of claim 9, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL. 52. The method of claim 9, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL. 53. The method of claim 10, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ng/mL. 54. The method of claim 10, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL. 55. The method of claim 10, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL. 56. The method of claim 14, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ng/mL. 57. The method of claim 14, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL. 58. The method of claim 14, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL. 59. The method of claim 15, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.4 ng/mL. 60. The method of claim 15, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.3 ng/mL. 61. The method of claim 15, wherein after administration of the pharmaceutical formulation to the renally impaired patient, the average Cmax of oxymorphone over a 12-hour period is less than about 1.2 ng/mL.