PHARMACEUTICAL COMPOSITIONS
The present invention provides for a pharmaceutical composition that includes tetrabenazine and a release-retarding agent; and a method of treating a hyperkinetic movement disorder (e.g., Huntington's disease, chorea associated with Huntington's disease, hemiballismus, senile chorea, tic disorders, tardive dyskinesia, myoclonus, dystonia and/or Tourette's syndrome). The method includes administering an effective amount of the pharmaceutical composition, for a period of time effective to treat the hyperkinetic movement disorder.
1 . A pharmaceutical composition comprising tetrabenazine and a release-retarding agent, wherein the tetrabenazine comprises about 5% (w/w) to about 20% (w/w) of the composition.
2 . The pharmaceutical composition of claim 1 , in an oral unit dosage form, wherein the oral unit dosage form comprises:
(i) about 10 mg of tetrabenazine;
(ii) about 12.5 mg of tetrabenazine;
(iii) about 15 mg of tetrabenazine;
(iv) about 20 mg of tetrabenazine;
(v) about 25 mg of tetrabenazine;
(vi) about 30 mg of tetrabenazine; or
(vii) about 50 mg of tetrabenazine.
3 . The pharmaceutical composition of claim 1 , wherein the tetrabenazine is the sole therapeutic agent.
4 . The pharmaceutical composition of claim 1 , wherein the tetrabenazine is combined with a second therapeutic agent selected from the group consisting of an antidepressant, anticholinergic, antiepileptic, anti-Parkinsons agent, antipsychotic, aricept, baclofen, barbiturate, benzodiazepine, beta-blocker, botulinum toxin, calcium channel antagonist, catecholamine-depleting agent, clomiplamine, clonidine, clonazepam, clozapine, diphenhydramine, dopaminergic drug, dopamine agonist, fluphenazine, guanfacine, haloperidol, 5-hydroxytryptophan, keppra, L-dopa, methylphenidate, metoclopramide, mirapex, muscle relaxant, neuroleptics, olanzapine, perphenazine, phenytoin, pimozide, piquindone, piracetam, primidone, psychostimulant, requip, risperidone, selegiline, serotonin reuptake inhibitor, sertraline, sodium valproate, sulpiride, tiapride, tricyclic antidepressants, trihexyphenidyl, trihexyphenidyl-hydrochloride (Pakisonal), ziprasidone, and combinations thereof.
5 . (canceled)
6 . (canceled)
7 . The pharmaceutical composition of claim 1 , further comprising at least one of a diluent, disintegrant, glidant and lubricant.
8 . The pharmaceutical composition of claim 7 , wherein the diluent is a sugar.
9 . The pharmaceutical composition of claim 8 , wherein the sugar is lactose.
10 . The pharmaceutical composition of claim 7 , wherein the diluent comprises about 30% (w/w) to about 40% (w/w) of the composition, the disintegrant comprises about 15% (w/w) to about 30% (w/w) of the composition, or wherein the glidant comprises about 1% (w/w) to about 2% (w/w) of the composition.
11 . The pharmaceutical composition of claim 7 , wherein the disintegrant is starch.
12 . (canceled)
13 . The pharmaceutical composition of claim 7 , wherein the glidant is talc, colloidal silicon dioxide, or a combination thereof.
14 . (canceled)
15 . The pharmaceutical composition of claim 7 , wherein the lubricant is magnesium stearate.
16 . The pharmaceutical composition of claim 7 , wherein the lubricant comprises about 0.1 (w/w) to about 2% (w/w) of the composition.
17 . (canceled)
18 . (canceled)
19 . (canceled)
20 . The pharmaceutical composition of claim 1 , wherein the release-retarding agent comprises an agent selected from a cellulose derivative, a polyoxyalkylene block co-polymer, and mixtures thereof.
21 . (canceled)
22 . (canceled)
23 . The pharmaceutical composition of claim 1 , wherein the release-retarding agent comprises about 20% (w/w) to about 40% (w/w) of the composition.
24 . (canceled)
25 . A method of treating a hyperkinetic movement disorder, the method comprising administering an effective amount of the pharmaceutical composition of claim 1 , for a period of time effective to treat the hyperkinetic movement disorder.
26 . (canceled)
27 . The method of claim 25 , wherein the pharmaceutical composition comprises a second therapeutic agent.
28 . The method of claim 27 , wherein the second therapeutic agent is: an antidepressant, anticholinergic, antiepileptic, an anti-Parkinsons agent, antipsychotic, aricept, baclofen, barbiturate, benzodiazepine, beta-blocker, botulinum toxin, calcium channel antagonist, catecholamine-depleting agent, clomiplamine, clonidine, clonazepam, clozapine, diphenhydramine, dopaminergic drug, dopamine agonist, fluphenazine, guanfacine, haloperidol, 5-hydroxytryptophan, keppra, Ldopa, methylphenidate, metoclopramide, mirapex, muscle relaxant, neuroleptics, olanzapine, perphenazine, phenytoin, pimozide, piquindone, piracetam, primidone, psychostimulant, requip, risperidone, selegiline, serotonin reuptake inhibitor, sertraline, sodium valproate, sulpiride, tiapride, tricyclic antidepressants, trihexyphenidyl, trihexyphenidyl-hydrochloride (Pakisonal), ziprasidone, or a combination thereof.
29 . The method of claim 25 , wherein the pharmaceutical composition is administered within about 1 hour, before or after, of ingesting food.
30 . (canceled)
31 . The method of claim 29 , wherein the Fed/Fast ratio of the systemic exposure (AUC) of each of the active metabolites alpha- and beta-dihydrotetrabenazine is at least about 140% or at least about 220% and wherein the Cmax of each of the active metabolites is obtained between about 3 hours and about 6 hours after administration of the composition.
32 . (canceled)
33 . (canceled)
34 . The method of claim 25 , wherein the pharmaceutical composition is administered about once a day (q.d.) or about twice a day (b.i.d.).
35 . (canceled)
36 . (canceled)
37 . (canceled)
38 . The method of claim 25 , wherein the patient experiences a lower incidence or severity of adverse effects, as compared to an immediate release composition that contains tetrabenazine.
39 . (canceled)
40 . The method of claim 38 , wherein the adverse effects comprise at least one of akathisia, depression, suicidal thoughts, suicidal behavior (suicidality), dizziness, drowsiness, sedation, somnolence, insomnia, fatigue, nervousness, anxiety, nausea and Parkinsonism.