Compositions for reduction of side effects
The present invention provides drug therapy formulations. In some embodiments, the present invention provides combinations of pharmaceutical agents (e.g., stimulant and non-stimulant), pharmaceutical formulations (e.g., nanoparticualte, non-nanoparticualte, etc.), and release profiles (e g, immediate release, delayed release, sustained release, etc.) to provide therapeutic benefit with reduced side effects.
1. A method of treating ADHD in a subject having a disorder that may cause tics, the method comprising: administering to the subject a once daily dose of a pharmaceutical composition comprising:
a) dexamphetamine nanoparticulate formulated for rapid release and rapid onset of therapeutic action; and
b) guanfacine;
wherein the pharmaceutical composition is formulated for sequential release of the dexamphetamine and the guanfacine.
2. The method of claim 1 , wherein the pharmaceutical composition is formulated such that the pharmaceutical composition provides a reduction in side effects compared to a therapeutic once-daily dose of 10 mg of said dexamphetamine administered alone.
3. The method of claim 2 , wherein said reduction in side effects comprises reduction in tics.
4. The method of claim 3 , wherein said reduction in side effects further comprises reduction in one or more of appetite suppression, insomnia, and gastrointestinal pain.
5. The method of claim 1 , wherein the pharmaceutical composition is formulated for sequential release of the dexamphetamine between 0.15 hours or less and 2 hours and guanfacine between 3 and 12 hours.
6. The method of claim 1 , wherein the guanfacine is coated for enteric release.
7. The method of claim 1 , wherein the pharmaceutical composition comprises 20 mg or less of dexamphetamine.
8. The method of claim 7 , wherein the pharmaceutical composition comprises less than 10 mg of dexamphetamine.
9. The method of claim 1 , wherein the pharmaceutical composition comprises 1.5 mg or less of the guanfacine.
10. The method of claim 9 , wherein the pharmaceutical composition comprises less than 1 mg of the guanfacine.
11. The method of claim 1 , wherein the pharmaceutical composition further comprises l-amphetamine formulated for release with the dexamphetamine.
12. The method of claim 1 , wherein the pharmaceutical composition further comprises peppermint oil.
13. The method of claim 1 , wherein said nanoparticulate formulated dexamphetamine has particles with a mean diameter between 100-500 nm.
14. The method of claim 1 , wherein said pharmaceutical composition is formulated to provide a peak blood concentration of said dexamphetamine in less than 15 minutes after administration.
15. The method of claim 1 , wherein said pharmaceutical composition further comprises an agent to deter abuse of said pharmaceutical composition.
16. The method of claim 1 , wherein said pharmaceutical composition is provided in a once-daily dosage as a tablet, capsule, orally-disintegrating tablets, pill, powder, elixir, syrup, suspension, lozenge, or spray.
17. The method of claim 1 , wherein the subject is a human child under the age of 18.
18. The method of claim 1 , wherein the subject is a human adult.
19. The method of claim 1 , wherein said administration produces three release peaks in the plasma of said subject.
20. The method of claim 19 , wherein said three release peaks are two dexamphetamine peaks and one guanfacine peak.
21. The method of claim 1 , wherein said dexamphetamine nanoparticulate formulated for rapid release and rapid onset of therapeutic action is prepared by a method comprising milling said dexamphetamine in ethanol to produce a dry powder nanoparticulate dexamphetamine.