Methods and compositions for safe and effective treatment of erythema

1. A method of treating erythema or a symptom associated therewith in a subject, comprising topically administering to a skin area affected by the erythema or the symptom a topical composition comprising, relative to the total weight of the composition, 0.4% to 0.6% by weight of brimonidine, and a pharmaceutically acceptable carrier, wherein the topical administration effects a serum or plasma profile of brimonidine having a mean C max of about 54±28 pg/mL or less and a mean AUC 0-24 hr hr of about 568±277 pg.hr/mL or less.

2. The method of claim 1 , wherein the erythema is erythema of rosacea.

3. The method of claim 1 , further comprising providing to the subject at least one additional treatment and medication for erythema or the symptom associated therewith.

4. The method of claim 1 , wherein the topical composition is administered to the skin area once daily.

5. The method of claim 1 , wherein the topical administration of the topical composition to the skin area results in more reduction of the erythema or the symptom compared to a vehicle control as measured by a 12 hour success profile evaluated on both Clinician's Erythema Assessment scores and Patient's Self Assessment scales, wherein the 12 hour success profile comprises an effect of 1-grade improvement of the erythema or the symptom and about 1 hour to about 8 hours of 2-grade improvement of the erythema or the symptom.

6. The method of claim 5 , wherein the erythema or the symptom is facial erythema associated with rosacea, and the 12 hour success profile comprises an effect of 1-grade improvement of the facial erythema and about 3 hours to about 6 hours of 2-grade improvement of the facial erythema.

7. The method of claim 1 , wherein the brimonidine is brimonidine tartrate.

8. The method of claim 7 , wherein the topical composition comprises about 0.5% by weight of brimonidine tartrate relative to the total weight of the composition.

9. The method of claim 1 , wherein the topical composition further comprises about 0.50% to about 2.0% by weight of a gelling agent relative to the total weight of the composition, and the gelling agent comprises a carbomer.

10. The method of claim 9 , wherein the carbomer is selected from the group consisting of carbomer 934P, carbomer 974P, and carbomer 980.

11. The method of claim 1 , wherein the topical composition further comprises about 0.04% to about 0.08% by weight of water dispersible form of titanium dioxide relative to the total weight of the composition.

12. The method of claim 1 , wherein the topical composition further comprises a preservative selected from the group consisting of sodium benzoate, phenoxyethanol, benzyl alcohol, methylparaben, imidazolidinyl urea and diazolidinyl urea.

13. The method of claim 1 , wherein the topical composition further comprises about 5.0% to about 15.0% by weight of at least one polyol relative to the total weight of the composition.

14. A method of producing a packaged product for treating erythema or a symptom associated therewith in a subject, comprising:

(1) obtaining a topical composition comprising, relative to the total weight of the composition, 0.4% to 0.6% by weight of brimonidine, and a pharmaceutically acceptable carrier;

(2) devising instructions for topically administering the topical composition to a skin area affected by the erythema or the symptom to obtain the treatment, and

(3) providing the topical composition and the instructions in a unified package for the subject,

wherein the topical administration effects a serum or plasma profile of brimonidine having a mean C max of about 54±28 pg/mL or less and a mean AUC 0-24 hr of about 568±277 pg.hr/mL or less.

15. A topical composition for treating erythema or a symptom associated therewith in a subject, the composition comprising, relative to the total weight of the composition:

0.4% to 0.6% by weight of brimonidine;

and a pharmaceutically acceptable carrier,

wherein the topical administration of the topical gel composition to a skin area affected by the erythema or the symptom effects a serum or plasma profile of brimonidine having a mean C max of about 54±28 pg/mL or less and a mean AUC 0-24 hr of about 568±277 pg.hr/mL or less.

16. The topical gel composition of claim 15 , wherein the brimonidine is brimonidine tartrate.

17. The topical gel composition of claim 16 , comprising about 0.5% by weight of brimonidine tartrate relative to the total weight of the composition.

18. The topical gel composition of claim 15 , further comprising about 0.50% to about 2.0% by weight of a gelling agent relative to the total weight of the composition, and the gelling agent comprises a carbomer.

19. The topical gel composition of claim 15 , wherein the topical composition further comprises about 5.0% to about 15.0% by weight of one polyol relative to the total weight of the composition.

20. The method of claim 1 , wherein the erythema or the symptom associated therewith is facial erythema associated with rosacea, and the topical composition comprises about 0.5% by weight of brimonidine tartrate relative to the total weight of the composition.

21. The topical composition of claim 15 , wherein the topical administration of the topical composition to the skin area results in more reduction of the erythema or the symptom compared to a vehicle control as measured by a 12 hour success profile evaluated on both Clinician's Erythema Assessment scores and Patient's Self Assessment scales, wherein the 12 hour success profile comprises an effect of 1-grade improvement of the erythema or the symptom and about 1 hour to about 8 hours of 2-grade improvement of the erythema or the symptom.

22. The topical composition of claim 21 , wherein the erythema or the symptom is facial erythema associated with rosacea, and the 12 hour success profile comprises an effect of 1-grade improvement of the facial erythema and about 3 hours to about 6 hours of 2-grade improvement of the facial erythema.