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 composition 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 composition requires no dilution before administration and has a pH from about 3.6 to about 4.7, the composition when stored in 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 composition 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 composition requires no dilution before administration and has a pH from about 3.6 to about 4.7, the composition when stored in a 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

from about 0.01 to about 0.1 mg/mL citric acid;

the aqueous solution contained in a pharmaceutically acceptable container such that the solution does not come into contact with polar polymers;

the aqueous solution when stored in the container for at least one year at room temperature exhibiting (i) less than a 10% decrease in the concentration of nicardipine hydrochloride and (ii) a total impurity formation of less than about 3%;

wherein the administering does not comprise diluting the aqueous solution prior to administration.

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 container comprises 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;

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; and

from about 0.0192 to about 0.0384 mg/mL citric acid.

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

from about 0.01 to about 0.1 mg/mL citric acid;

the aqueous solution contained in a pharmaceutically acceptable container such that the solution does not come into contact with polar polymers;

the aqueous solution when stored in the container for at least one year at room temperature exhibiting (i) less than a 10% decrease in the concentration of nicardipine hydrochloride and (ii) a total impurity formation of less than about 3%;

wherein the administering does not comprise diluting the aqueous solution prior to administration.

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 container comprises 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;

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; and

from about 0.0192 to about 0.0384 mg/mL citric acid.