Use of NK-1 receptor antagonists in pruritus
View Patent ↗The invention relates to methods for treating pruritus with NK-1 receptor antagonists such as serlopitant. The invention further relates to pharmaceutical compositions comprising NK-1 receptor antagonists such as serlopitant. In addition, the invention encompasses treatment of a pruritus-associated condition with serlopitant and an additional antipruritic agent, and the use of serlopitant as a sleep aid, optionally in combination with an additional sleep-aiding agent.
1. A method of treating pruritus, comprising administering a therapeutically effective amount of 3-[(3aR,4R,5S,7aS)-5-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-4-(4-fluorophenyl)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]cyclopent-2-en-1-one (serlopitant) or a pharmaceutically acceptable salt, solvate or polymorph thereof to a patient in need of treatment.
2. The method of claim 1 , wherein the therapeutically effective amount of serlopitant comprises a dosage of 0.10 mg, 0.15 mg, 0.20 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 15 mg, 20 mg, 25 mg or 30 mg one or more times a day.
3. The method of claim 2 , wherein the therapeutically effective amount of serlopitant comprises a dosage of 0.25 mg, 1 mg or 5 mg once a day.
4. The method of claim 1 , wherein the therapeutically effective amount of serlopitant comprises a dosage of from about 0.1 mg to about 30 mg, or from about 1 mg to about 7.5 mg.
5. The method of claim 1 , wherein serlopitant is administered once a day, once every other day, once every third day, once every fourth day, or once a week.
6. The method of claim 1 , wherein serlopitant is administered over a period of at least two weeks or 1 month.
7. The method of claim 1 , wherein serlopitant is administered at bedtime.
8. The method of claim 1 , wherein serlopitant is administered orally.
9. The method of claim 1 , wherein serlopitant is administered topically.
10. The method of claim 9 , wherein serlopitant is administered dermally or transdermally.
11. The method of claim 1 , wherein the pruritus is chronic pruritus.
12. The method of claim 1 , wherein the pruritus is associated with prurigo, a genetic disease or a liver disease.
13. The method of claim 12 , wherein the prurigo is prurigo nodularis, the genetic disease is epidermolysis bullosa, and the liver disease is liver failure.
14. The method of claim 1 , further comprising administering one or more additional antipruritic agents.
15. The method of claim 14 , wherein the one or more additional antipruritic agents are selected from the group consisting of antihistamines, corticosteroids, immunomodulators, immunosuppressants, antidepressants and anticonvulsants.
16. The method of claim 15 , wherein:
the antihistamines are non-sedating second-generation and third-generation antihistamines;
the corticosteroids are corticosteroids having moderate or medium potency;
the immunomodulators and immunosuppressants are selected from antimetabolites and calcineurin inhibitors;
the antidepressants are serotonin-norepinephrine reuptake inhibitors; and
the anticonvulsants are selected from carbamazepine, gabapentin, pregabalin, and valproic acid and salts thereof.
17. The method of claim 16 , wherein:
the non-sedating second-generation and third-generation antihistamines are selected from acrivastine, astemizole, azelastine, bepotastine, bilastine, cetirizine, levocetirizine, ebastine, fexofenadine, ketotifen, levocabastine, loratadine, desloratadine, mizolastine, olopatadine, quifenadine, rupatadine and terfenadine;
the corticosteroids having moderate or medium potency are selected from amcinonide 0.1%, betamethasone dipropionate 0.05%, betamethasone valerate 0.1%, clobetasone butyrate 0.05%, desonide 0.05%, fluocinolone acetonide 0.01-0.2%, flurandrenolide 0.05%, fluticasone propionate 0.005%, fluticasone propionate 0.05%, halometasone 0.05%, hydrocortisone butyrate 0.1%, hydrocortisone valerate 0.2%, mometasone furoate 0.1%, triamcinolone acetonide 0.025-0.5%, and triamcinolone diacetate 0.5%;
the antimetabolites are antifolates, and the calcineurin inhibitors are selected from cyclosporin, pimecrolimus and tacrolimus; and
the serotonin-norepinephrine reuptake inhibitors are selected from bicifadine, duloxetine, milnacipran, levomilnacipran, sibutramine, venlafaxine and desvenlafaxine.
18. The method of claim 14 , wherein the one or more additional antipruritic agents are administered topically.
19. The method of claim 18 , wherein the one or more additional antipruritic agents are administered dermally or transdermally.