Droxidopa and pharmaceutical composition thereof for the treatment of fibromyalgia

Abstract

The present invention provides methods of treating fibromyalgia or other diseases or conditions causing widespread pain and/or fatigue. In particular, the invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active agents, that can be used in the inventive methods. The methods of treatment can comprise treating, preventing, reducing, or eliminating a variety of symptoms recognized as indicative of fibromyalgia, such as chronic pain, allodynia, hyperalgesia, fatigue, sleep disturbance, and depression.

1 . A kit comprising a container including one or more therapeutically effective doses of a pharmaceutical composition comprising droxidopa, and an instruction set describing a method for administering the pharmaceutical composition to a subject suffering from fibromyalgia in a therapeutically effective amount to treat the fibromyalgia. 
     
     
         2 . The kit according to  claim 1 , wherein the instruction set describes a method for administering the pharmaceutical composition to the subject in a therapeutically effective amount to treat a symptom associated with the fibromyalgia. 
     
     
         3 . The kit according to  claim 2 , wherein the symptom is pain associated with fibromyalgia. 
     
     
         4 . The kit according to  claim 2 , wherein treating comprises reducing the severity of the symptom. 
     
     
         5 . The kit according to  claim 2 , wherein the instruction set describes a method for administering the pharmaceutical composition to the subject in a therapeutically effective amount to reduce pain associated with the fibromyalgia. 
     
     
         6 . The kit according to  claim 1 , wherein the pharmaceutical composition is in a solid form. 
     
     
         7 . The kit according to  claim 6 , wherein the solid form is a tablet, caplet, capsule, or wafer. 
     
     
         8 . The kit according to  claim 1 , wherein the pharmaceutical composition is in a delayed release form. 
     
     
         9 . The kit according to  claim 1 , wherein the pharmaceutical composition is in a sustained release form. 
     
     
         10 . The kit according to  claim 1 , wherein the pharmaceutical composition comprises about 10 mg to about 2 g of droxidopa. 
     
     
         11 . The kit according to  claim 10 , wherein the pharmaceutical composition comprises about 50 mg to about 750 mg of droxidopa. 
     
     
         12 . The kit according to  claim 10 , wherein the pharmaceutical composition comprises about 80 mg to about 600 mg of droxidopa. 
     
     
         13 . The kit according to  claim 10 , wherein the pharmaceutical composition comprises about 100 mg to about 500 mg of droxidopa. 
     
     
         14 . The kit according to  claim 1 , wherein the pharmaceutical composition comprises one or more additional active agents selected from the group consisting of DOPA decarboxylase inhibiting compounds, catechol-O-methyltransferase inhibitors, cholinesterase inhibitors, antidepressants, anti-inflammatories, muscle relaxants, antibiotics, mood stabilizers, antipsychotics, serotonin receptor antagonists, serotonin receptor agonists, pain relievers, stimulants, NMDA receptor ligands, s-adenosyl-methionine, zopiclone, chlormezanone, proglumetacin, 5-OH-L-tryptophan, gabapentin, pregabalin, tamoxefin, and combinations thereof. 
     
     
         15 . The kit according to  claim 14 , wherein the one or more additional active agents comprise one or more DOPA decarboxylase inhibiting compounds selected from the group consisting of benserazide, carbidopa, difluoromethyldopa, a-methyldopa, and combinations thereof. 
     
     
         16 . The kit according to  claim 14 , wherein the one or more additional active agents comprise one or more catechol-O-methyltransferase inhibitors selected from the group consisting of entacapone, tolcapone, nitecapone, and combinations thereof 
     
     
         17 . The kit according to  claim 14 , wherein the one or more additional active agents comprise one or more cholinesterase inhibitors selected from the group consisting of pyridostigmine, donepezil, rivastigmine, galantamine, tacrine, neostigmine, metrifonate, physostigmine, ambenonium, edrophonium, demarcarium, thiaphysovenine, phenserine, cymserine, and combinations thereof 
     
     
         18 . The kit according to  claim 14 , wherein the one or more additional active agents comprise one or more antidepressants. 
     
     
         19 . The kit according to  claim 14 , wherein the antidepressant is a monoamine oxidase inhibitor selected from the group consisting of isocarboxazid, moclobemide, phenelzine, tranylcypromine, selegiline, lazabemide, nialamide, iproniazid, iproclozide, toloxatone, harmala, brofaromine, benmoxin, 5-Methoxy-N,N-dimethyltryptamine, 5-methoxy-α-methyltryptamine, and combinations thereof 
     
     
         20 . The kit according to  claim 19 , wherein the antidepressant is selected from the group consisting of selective serotonin reuptake inhibitors, tricyclics, serotonin norepinephrine reuptake inhibitors, norepinephrine reuptake inhibitors, norepinephrine and dopamine reuptake inhibitors, and combinations thereof 
     
     
         21 . The kit according to  claim 19 , wherein the antidepressant is selected from the group consisting of fluoxetine, paroxetine, citalopram, escitalopram, fluvoxamine, sertraline, amitriptyline, nortriptyline, desipramine, trazodone, venlafaxine, duloxetine, milnacipran, nefopam, bupropion, and combinations thereof. 
     
     
         22 . The kit according to  claim 14 , wherein the pharmaceutical composition comprises the droxidopa and the one or more additional compounds in a ratio of about 500:1 to about 1:10. 
     
     
         23 . The kit according to  claim 22 , wherein the pharmaceutical composition comprises the droxidopa and the one or more additional compounds in a ratio of about 80:1 to about 1:1. 
     
     
         24 . The kit according to  claim 22 , wherein the pharmaceutical composition comprises the droxidopa and the one or more additional compounds in a ratio of about 50:1 to about 2:1. 
     
     
         25 . The kit according to  claim 22 , wherein the pharmaceutical composition comprises the droxidopa and the one or more additional compounds in a ratio of about 20:1 to about 3:1. 
     
     
         26 . The kit according to  claim 14 , wherein the one or more additional active agents is a DOPA decarboxylase inhibiting compound. 
     
     
         27 . The kit according to  claim 26 , wherein the DOPA decarboxylase inhibiting compound is carbidopa. 
     
     
         28 . The kit according to  claim 26 , wherein the pharmaceutical composition comprises about 50 mg to about 750 mg of droxidopa, and wherein the droxidopa and the DOPA decarboxylase inhibiting compound are in a ratio of about 80:1 to about 1:1. 
     
     
         29 . The kit according to  claim 28 , wherein the droxidopa and the DOPA decarboxylase inhibiting compound are in a ratio of about 50:1 to about 2:1. 
     
     
         30 . The kit according to  claim 26 , wherein the pharmaceutical composition comprises a further active agent. 
     
     
         31 . The kit according to  claim 30 , wherein the further active agent is selected from the group consisting of catechol-O-methyltransferase inhibitors, cholinesterase inhibitors, antidepressants, anti-inflammatories, muscle relaxants, antibiotics, mood stabilizers, antipsychotics, serotonin receptor antagonists, serotonin receptor agonists, pain relievers, stimulants, NMDA receptor ligands, s-adenosyl-methionine, zopiclone, chlormezanone, proglumetacin, 5-OH-L-tryptophan, gabapentin, pregabalin, tamoxefin, and combinations thereof. 
     
     
         32 . The kit according to  claim 31 , wherein the further active agent is a serotonin norepinephrine reuptake inhibitor or pregabalin. 
     
     
         33 . The kit according to  claim 1 , wherein the instruction set describes administering the pharmaceutical composition once daily. 
     
     
         34 . The kit according to  claim 1 , wherein the instruction set describes administering the pharmaceutical composition twice daily. 
     
     
         35 . The kit according to  claim 1 , wherein the instruction set describes administering the pharmaceutical composition three times daily.