Metaxalone products, method of manufacture, and method of use

Abstract

Disclosed herein are methods of using metaxalone. In one embodiment, the method comprises determining that a patient in need metaxalone therapy is taking a substance that is a n inhibitor or an inducer of a cytochrome p450 isozyme, wherein the cytochrome P450 is CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4, and adjusting administration to the patient of metaxalone or the substance to avoid an adverse event associated with metaxalone. In another embodiment, the method comprises informing a user that metaxalone ais metabolized by a cytochrome p450 isozyme, wherein the cytochrome P450 is CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4. Also included are articles of manufacture comprising a container containing a dosage form of metaxalone, wherein the container is associated with published material informing that metaxalone affects activity of a cytochrome p450 isozyme. Also disclosed are a method of treatment and a method of manufacturing a metaxalone product.

1 .- 13 . (canceled) 
     
     
         14 . A method of preventing sedation in a patient in need of metaxalone comprising
 determining a dosing regimen for metaxalone to be administered to a patient in need thereof,   determining that a substance that is a known inhibitor of a cytochrome P450 isozyme (CYP) selected from CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 is currently administered or will be administered to the patient, and   altering dosing of metaxalone administered to the patient from the determined dosing regimen while the known inhibitor of the CYP is coadministered to the patient to prevent sedation.   
     
     
         15 . The method of  claim 14  further comprising
 monitoring plasma concentration of metaxalone in the patient after administration of metaxalone to the patient.   
     
     
         16 . The method of  claim 14 , wherein altering dosing of metaxalone comprises
 decreasing a dose of metaxalone administered to the patient; or   decreasing a number of doses per day administered to the patient.   
     
     
         17 . The method of  claim 14 , wherein the determined dosing regimen is 800 mg, three or four times daily. 
     
     
         18 . The method of  claim 14  wherein the CYP is CYP3A4 and the known inhibitor of CYP3A4 is an HIV antiviral, delavirdine, indinavir, nelfinavir, ritonavir; amiodarone, aprepitant, cinchloramphenicol, cimetidine, clarithromycin, diethyl-dithiocarbamate, diltiazem, erythromycin, fluconazole, fluvoxamine, gestodene, grapefruit juice, Seville orange juice, imatinib, itraconazole, ketoconazole, mifepristone, nefazodone, norfloxacin, norfluoxetine, mibefradil, star fruit, verapamil, or voriconazole;
 the CYP is CYP1A2 and the known inhibitor of CYP1A2 is amiodarone, cimetidine, a fluoroquinolone, fluvoxamine, furafylline, interferon, methoxsalen, or mibefradil; or   the CYP is CYP2E1 and the known inhibitor of CYP2E1 is diethyl-dithiocarbamate or disulfuram.   
     
     
         19 . A method of optimizing the dose of metaxalone to administer to a patient in need of a skeletal muscle relaxant, comprising
 determining that a substance that is a known inducer or a known inhibitor of a cytochrome P450 isozyme (CYP) selected from CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 is administered to a patient in need of a skeletal muscle relaxant; and   optimizing a dose of metaxalone administered to the patient by administering a dose of metaxalone greater than a standard dose if a known inducer of the CYP is administered to the patient or administering a dose less than the standard dose of metaxalone if a known inhibitor of the CYP is administered to the patient.   
     
     
         20 . The method of  19 , wherein the standard dose of metaxalone is 800 mg. 
     
     
         21 . The method of  claim 19 , further comprising
 optimizing a frequency per day at which the optimized dose is taken by the patient.   
     
     
         22 . The method of  claim 19 , further comprising
 monitoring plasma concentration of metaxalone in the patient to determine if the patient is at risk of a subtherapeutic outcome or of a metaxalone toxicity; and   optimizing the dose of metaxalone administered to the patient to alleviate the risk.   
     
     
         23 .- 37 . (canceled) 
     
     
         38 . A method of avoiding an adverse event when administering metaxalone, comprising
 determining that a patient in need of metaxalone therapy is taking a substance that is a known inhibitor or a known inducer of cytochrome P450 isozyme (CYP) selected from CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4, and   adjusting administration to the patient of metaxalone or the substance to avoid an adverse event associated with a change in the metabolism of metaxalone.   
     
     
         39 . The method of  claim 38 , wherein the method further comprises
 informing the patient or the patient's medical care worker that administration of metaxalone with a substance that is a known inhibitor of the CYP can result in increased plasma concentration of metaxalone;   informing the patient or the patient's medical care worker that administration of metaxalone with a substance that is a known inducer of the CYP can result in decreased plasma concentration of metaxalone; or   monitoring the patient.   
     
     
         40 .- 64 . (canceled) 
     
     
         65 . The method of  claim 19 , wherein the CYP is CYP1A2, CYP2E1, or CYP3A4. 
     
     
         66 . The method of  claim 19 , wherein the CYP is CYP3A4, and the substance is
 an inhibitor of CYP3A4 selected from an HIV antiviral; amiodarone, aprepitant, cinchloramphenicol, cimetidine, clarithromycin, diethyl-dithiocarbamate, diltiazem, erythromycin, fluconazole, fluvoxamine, gestodene, grapefruit juice, Seville orange juice, imatinib, itraconazole, ketoconazole, mifepristone, nefazodone, norfloxacin, norfluoxetine, mibefradil, star fruit, verapamil, and voriconazole; or   an inducer of CYP3A4 selected from an HIV Antiviral; a barbiturate, carbamazepine, efavirenz, a glucocorticoid, modafinil, nevirapine, phenobarbital, phenyloin, rifampin, St. John's wort, troglitazone, oxcarbazepine, pioglitazone, and rifabutin.   
     
     
         67 . The method of  claim 19 , wherein the CYP is CYP1A2, and the substance is
 an inhibitor of CYP1A2 selected from amiodarone, cimetidine, a fluoroquinolone, fluvoxamine, furafylline, interferon, methoxsalen, and mibefradil; or   an inducer of CYP1A2 selected from insulin, methyl cholanthrene, modafinil, nafcillin, beta-naphthoflavone, omeprazole, and tobacco.   
     
     
         68 . The method of  claim 19 , wherein the CYP is CYP2E1, and the substance is
 an inhibitor of CYP2E1 selected from diethyl-dithiocarbamate and disulfuram; or   an inducer of CYP2E1 selected from ethanol and isoniazid.   
     
     
         69 . The method of  claim 39 , wherein monitoring the patient comprises:
 monitoring the patient's plasma concentration of metaxalone;   monitoring the patient for a symptom of an active agent interaction between the substance and metaxalone;   monitoring the patient for an adverse reaction resulting from coadministration of the substance and metaxalone;   monitoring the patient for an adverse reaction associated with metaxalone;   monitoring the patient for a metaxalone-associated toxicity;   monitoring the patient for a sub-therapeutic outcome for metaxalone;   monitoring the patient for reduced efficacy of metaxalone;   monitoring the patient for an adverse reaction or sub-therapeutic outcome associated with reduced plasma concentration of metaxalone; or   monitoring the patient for an adverse reaction associated with an elevated plasma concentration of metaxalone.