Methods of treatment with pre-mixed, ready-to-use pharmaceutical compositions

1. A method for treating acute elevations of blood pressure in a human subject in need thereof, said method comprising parenterally administering a pre-mixed aqueous solution comprising from about 0.1 to 0.4 mg/mL nicardipine or a pharmaceutically acceptable salt thereof; a tonicity agent; and a buffer; wherein the aqueous solution requires no dilution before administration and has a pH from about 3.6 to about 4.7, the aqueous solution stored in a container such that the aqueous solution is in contact with non-polar polymers, the aqueous solution when stored in the container for at least three months at room temperature exhibiting (i) less than a 10% decrease in the concentration of nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity formation of less than about 3%.

2. A method for inducing hypotension in a human subject in need thereof, said method comprising parenterally administering a pre-mixed aqueous solution comprising from about 0.1 to 0.4 mg/mL nicardipine or a pharmaceutically acceptable salt thereof; a tonicity agent; and a buffer; wherein the aqueous solution requires no dilution before administration and has a pH from about 3.6 to about 4.7, the aqueous solution stored in a container such that the aqueous solution is in contact with non-polar polymers, the aqueous solution when stored in the container for at least three months at room temperature exhibiting (i) less than a 10% decrease in the concentration of nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity formation of less than about 3%.

3. A method for treating acute elevations of blood pressure in a human subject in need thereof, said method comprising parenterally administering to a subject in need thereof, a pre-mixed aqueous solution with a pH from about 3.6 to about 4.7 comprising: from about 0.1 to 0.4 mg/mL nicardipine hydrochloride; a tonicity agent selected from (i) about 4.5% to about 5% dextrose or (ii) about 0.8% to about 0.9% sodium chloride; and a buffer; the aqueous solution contained in a pharmaceutically acceptable container such that the aqueous solution is in contact with non-polar polymers, the aqueous solution when stored in the container for at least three months at room temperature exhibiting (i) less than a 10% decrease in the concentration of nicardipine or pharmaceutically acceptable salt thereof and a total impurity formation of less than about 3%.

4. The method of claim 3 , further comprising at least one pH adjuster selected from the group consisting of hydrochloric acid, sodium hydroxide and a mixture thereof.

5. The method of claim 3 , further comprising from about 1 mg/ml to about 4 mg/ml sorbitol.

6. The method of claim 3 , wherein the non-polar polymers comprise copolyester, polyethylene or polyolefin.

7. The method of claim 3 , wherein the pre-mixed aqueous solution comprises: from about 0.1 to about 0.2 mg/mL nicardipine hydrochloride; and a tonicity agent selected from (i) about 46 to about 50 mg/mL dextrose or (ii) about 8.3 to about 9 mg/mL sodium chloride.

8. A method for inducing hypotension in a human subject in need thereof said method comprising parenterally administering to a subject in need thereof, a pre-mixed aqueous solution with a pH from about 3.6 to about 4.7 comprising: from about 0.1 to 0.4 mg/mL nicardipine hydrochloride; a tonicity agent selected from (i) about 4.5% to about 5% dextrose or (ii) about 0.8% to about 0.9% sodium chloride; and a buffer; the aqueous solution contained in a pharmaceutically acceptable container such that the solution is in contact with non-polar polymers, the aqueous solution when stored in the container for at least three months at room temperature exhibiting (i) less than a 10% decrease in the concentration of nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity formation of less than about 3%.

9. The method of claim 8 , further comprising at least one pH adjuster selected from the group consisting of hydrochloric acid, sodium hydroxide and a mixture thereof.

10. The method of claim 8 , further comprising from about 1 mg/ml to about 4 mg/ml sorbitol.

11. The method of claim 8 , wherein the non-polar polymers comprise copolyester, polyethylene or polyolefin.

12. The method of claim 8 , wherein the pre-mixed aqueous solution comprises: from about 0.1 to about 0.2 mg/mL nicardipine hydrochloride; and a tonicity agent selected from (i) about 46 to about 50 mg/mL dextrose or (ii) about 8.3 to about 9 mg/mL sodium chloride.

13. The method of claim 1 , wherein the wherein the non-polar polymers comprise copolyester, polyethylene or polyolefin.

14. The method of claim 2 , wherein the wherein the non-polar polymers comprise copolyester, polyethylene or polyolefin.

15. The method of claim 1 , wherein the non-polar polymers comprise polyethylene.

16. The method of claim 2 , wherein the non-polar polymers comprise polyethylene.

17. The method of claim 3 , wherein the non-polar polymers comprise polyethylene.

18. The method of claim 8 , wherein the non-polar polymers comprise polyethylene.

19. The method of claim 1 , wherein the aqueous solution when stored in the container for at least one year at room temperature exhibits (i) less than a 10% decrease in the concentration of nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity formation of less than about 3%.

20. The method of claim 2 , wherein the aqueous solution when stored in the container for at least one year at room temperature exhibits (i) less than a 10% decrease in the concentration of nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity formation of less than about 3%.

21. The method of claim 3 , wherein the aqueous solution when stored in the container for at least one year at room temperature exhibits (i) less than a 10% decrease in the concentration of nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity formation of less than about 3%.

22. The method of claim 8 , wherein the aqueous solution when stored in the container for at least one year at room temperature exhibits (i) less than a 10% decrease in the concentration of nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity formation of less than about 3%.

23. The method of claim 1 , further comprising from 0 mg/mL to about 4 mg/mL sorbitol.

24. The method of claim 2 , further comprising from 0 mg/mL to about 4 mg/mL sorbitol.

25. The method of claim 3 , further comprising from 0 mg/mL to about 4 mg/mL sorbitol.

26. The method of claim 8 , further comprising from 0 mg/mL to about 4 mg/mL sorbitol.

27. The method of claim 1 , wherein the pre-mixed aqueous solution comprises from about 0.1 to about 0.2 mg/mL nicardipine hydrochloride.

28. The method of claim 2 , wherein the pre-mixed aqueous solution comprises from about 0.1 to about 0.2 mg/mL nicardipine hydrochloride.