Composition and method for treating neurological disease
The present disclosure is directed to methods of treating neurological disorders in a patient such as Parkinson's disease, drug-induced extrapyramidal reactions, and/or levodopa-induced dyskinesia comprising administering to the patient once daily in the morning a pharmaceutical composition comprising about 50 mg to about 400 mg of extended-release amantadine or a pharmaceutically acceptable salt thereof.
1. A method of a drug-induced extrapyramidal reaction in an adult patient, comprising administering to the patient a pharmaceutical composition comprising i) an osmotic agent and amantadine or a pharmaceutically acceptable salt thereof in an extended release form, and ii) amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, wherein the composition comprises 258 mg of amantadine free base equivalent, and wherein the mean steady-state C avg of the composition is at least 95% of the mean steady-state C avg provided by the same daily quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
2. The method of claim 1 , wherein the mean steady-state C avg of the composition is at least 97% of the mean steady-state C avg provided by the same daily quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
3. The method of claim 2 , wherein the pharmaceutically acceptable salt thereof is amantadine HCl.
4. The method of claim 1 , wherein the pharmaceutical composition is an osmotic device.
5. The method of claim 4 , wherein the osmotic device comprises a semipermeable membrane.
6. The method of claim 1 , wherein the mean steady-state C avg for the composition is about 947 ng/mL.
7. A method of treating a drug-induced extrapyramidal reaction in an adult patient, comprising administering to the patient a pharmaceutical composition comprising i) an osmotic agent and amantadine or a pharmaceutically acceptable salt thereof in an extended release form, and ii) amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, wherein the composition comprises 258 mg of amantadine free base equivalent, and wherein the steady-state AUC 0-24 for the composition is at least 95% of the steady-state AUC 0-24 provided by the same daily quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
8. The method of claim 7 , wherein the steady-state AUC 0-24 for the composition is at least 97% of the steady-state AUC 0-24 provided by the same daily quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
9. The method of claim 8 , wherein the pharmaceutically acceptable salt thereof is amantadine HCl.
10. The method of claim 7 , wherein the pharmaceutical composition is an osmotic device.
11. The method of claim 10 , wherein the osmotic device comprises a semipermeable membrane.
12. The method of claim 7 , wherein the steady-state AUC 0-24 for the composition is about 22,737 ng·h/mL.
13. A method of treating a drug-induced extrapyramidal reaction in an adult patient, comprising administering to the patient a pharmaceutical composition comprising i) an osmotic agent and amantadine or a pharmaceutically acceptable salt thereof in an extended release form, and ii) amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, wherein the composition comprises 258 mg of amantadine free base equivalent, and wherein the steady-state C max of the composition is comparable to the steady-state C max provided by the same daily quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
14. The method of claim 13 , wherein the pharmaceutically acceptable salt thereof is amantadine HCl.
15. The method of claim 13 , wherein the pharmaceutical composition is an osmotic device.
16. The method of claim 15 , wherein the osmotic device comprises a semipermeable membrane.
17. The method of claim 13 , wherein the steady-state C max0-24 of the composition is about 1275 ng/mL.
18. A method of treating a drug-induced extrapyramidal reaction in an adult patient, comprising administering to the patient a pharmaceutical composition comprising i) an osmotic agent and amantadine or a pharmaceutically acceptable salt thereof in an extended release form, and ii) amantadine or a pharmaceutically acceptable salt thereof in an immediate release form, wherein the composition comprises 258 mg of amantadine free base equivalent, and wherein steady-state is achieved by about Day 6.
19. The method of claim 18 , wherein at steady-state the plasma concentration of the composition is at least 85% of the concentration provided by the same daily quantity of amantadine or a pharmaceutically acceptable salt thereof in an immediate release form.
20. The method of claim 18 , wherein the pharmaceutically acceptable salt thereof is amantadine HCl.
21. The method of claim 18 , wherein the pharmaceutical composition is an osmotic device.
22. The method of claim 21 , wherein the osmotic device comprises a semipermeable membrane.
23. The method of claim 18 , wherein at steady-state the plasma concentration of the composition is between about 609 and about 662 ng/mL.