Label: METAXALONE tablet

  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated January 20, 2020

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  • DESCRIPTION

    Metaxalone is available as an 800 mg, light pink to pink, capsule shaped, scored uncoated  tablet.

    Chemically, metaxalone is 5-[(3,5- dimethylphenoxy) methyl]-2-oxazolidinone. The empirical formula is C 12H 15NO 3, which corresponds to a molecular weight of 221.25. The structural formula is:

    chemical structure

    Metaxalone is a white to almost white, odorless crystalline powder freely soluble in chloroform, soluble in methanol and in 96% ethanol, but practically insoluble in ether or water.

    Each tablet contains 800 mg metaxalone and the following inactive ingredients: calcium carbonate, FD&C Red #40, hypromellose, lactose monohydrate, microcrystalline cellulose, povidone, silicone dioxide, sodium starch glycolate and sodium stearyl fumarate.

  • CLINICAL PHARMACOLOGY

    Mechanism of Action

    The mechanism of action of metaxalone in humans has not been established, but may be due to general central nervous system depression. Metaxalone has no direct action on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber.

    Pharmacokinetics

    The pharmacokinetics of metaxalone have been evaluated in healthy adult volunteers after single dose administration of metaxalone under fasted and fed conditions at doses ranging from 400 mg to 800 mg.

    Absorption

    Peak plasma concentrations of metaxalone occur approximately 3 hours after a 400 mg oral dose under fasted conditions. Thereafter, metaxalone concentrations decline log-linearly with a terminal half-life of 9.0 ± 4.8 hours. Doubling the dose of metaxalone from 400 mg to 800 mg results in a roughly proportional increase in metaxalone exposure as indicated by peak plasma concentrations (C max) and area under the curve (AUC). Dose proportionality at doses above 800 mg has not been studied. The absolute bioavailability of metaxalone is not known.

    The single-dose pharmacokinetic parameters of metaxalone in two groups of healthy volunteers are shown in Table 1.

    Table 1: Mean (%CV) Metaxalone Pharmacokinetic Parameters

    Dose (mg)

    C max

    (ng/mL)

    T max (h)

    AUC

    (ng•h/mL)

    t ½(h)

    CL/F

    (L/h)

    400 1

    983 (53)

    3.3 (35)

    7479 (51)

    9.0 (53)

    68 (50)

    800 2

    1816 (43)

    3.0 (39)

    15044 (46)

    8.0 (58)

    66 (51)

    1Subjects received 1x400 mg tablet under fasted conditions (N=42)

    2Subjects received 2x400 mg tablets under fasted conditions (N=59)

    Food Effects

    A randomized, two-way, crossover study was conducted in 42 healthy volunteers (31 males, 11 females) administered one 400 mg metaxalone tablet under fasted conditions and following a standard high-fat breakfast. Subjects ranged in age from 18 to 48 years (mean age = 23.5 ± 5.7 years). Compared to fasted conditions, the presence of a high fat meal at the time of drug administration increased C max by 177.5% and increased AUC (AUC 0-t, AUC ) by 123.5% and 115.4%, respectively. Time-to-peak concentration (T max) was also delayed (4.3 h versus 3.3 h) and terminal half-life was decreased (2.4 h versus 9.0 h) under fed conditions compared to fasted.

    In a second food effect study of similar design, two 400 mg metaxalone tablets (800 mg) were administered to healthy volunteers (N=59, 37 males, 22 females), ranging in age from 18 to 50 years (mean age = 25.6± 8.7 years). Compared to fasted conditions, the presence of a high fat meal at the time of drug administration increased C max by 193.6% and increased AUC (AUC 0-t, AUC ) by 146.4% and 142.2%, respectively. Time-to-peak concentration (T max) was also delayed (4.9 h versus 3.0 h) and terminal half-life was decreased (4.2 h versus 8.0 h) under fed conditions compared to fasted conditions. Similar food effect results were observed in the above study when one metaxalone 800 mg tablet was administered in place of two metaxalone 400 mg tablets. The increase in metaxalone exposure coinciding with a reduction in half-life may be attributed to more complete absorption of metaxalone in the presence of a high fat meal (Figure 1).

    figure 1

    Distribution, Metabolism, and Excretion

    Although plasma protein binding and absolute bioavailability of metaxalone are not known, the apparent volume of distribution (V/F ~ 800 L) and lipophilicity (log P = 2.42) of metaxalone suggest that the drug is extensively distributed in the tissues. Metaxalone is metabolized by the liver and excreted in the urine as unidentified metabolites. Hepatic Cytochrome P450 enzymes play a role in the metabolism of metaxalone. Specifically, CYP1A2, CYP2D6, CYP2E1, and CYP3A4 and, to a lesser extent, CYP2C8, CYP2C9, and CYP2C19 appear to metabolize metaxalone.

    Metaxalone does not significantly inhibit major CYP enzymes such as CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. Metaxalone does not significantly induce major CYP enzymes such as CYP1A2, CYP2B6, and CYP3A4 in vitro.

    Pharmacokinetics in Special Populations

    Age:

    The effects of age on the pharmacokinetics of metaxalone were determined following single administration of two 400 mg tablets (800 mg) under fasted and fed conditions. The results were analyzed separately, as well as in combination with the results from three other studies. Using the combined data, the results indicate that the pharmacokinetics of metaxalone are significantly more affected by age under fasted conditions than under fed conditions, with bioavailability under fasted conditions increasing with age.

    The bioavailability of metaxalone under fasted and fed conditions in three groups of healthy volunteers of varying age is shown in Table 2.

    Table 2: Mean (%CV) Pharmacokinetic Parameters Following Single Administration of Two 400 mg Metaxalone Tablets (800 mg) under Fasted and Fed Conditions

    Younger Volunteers

    Older Volunteers

    Age (years)

    25.6 ± 8.7

    39.3 ± 10.8

    71.5 ± 5.0

    N

    59

    21

    23

    Food

    Fasted

    Fed

    Fasted

    Fed

    Fasted

    Fed

    C max (ng/mL)

    1816

    (43)

    3510

    (41)

    2719

    (46)

    2915

    (55)

    3168

    (43)

    3680

    (59)

    T max (h)

    3.0

    (39)

    4.9

    (48)

    3.0

    (40)

    8.7

    (91)

    2.6

    (30)

    6.5

    (67)

    AUC 0-t (ng·h/mL)

    14531

    (47)

    20683

    (41)

    19836

    (40)

    20482

    (37)

    23797

    (45)

    24340

    (48)

    AUC (ng·h/mL)

    15045

    (46)

    20833

    (41)

    20490

    (39)

    20815

    (37)

    24194

    (44)

    24704

    (47)

    Gender:

    The effect of gender on the pharmacokinetics of metaxalone was assessed in an open label study, in which 48 healthy adult volunteers (24 males, 24 females) were administered two metaxalone 400 mg tablets (800 mg) under fasted conditions. The bioavailability of metaxalone was significantly higher in females compared to males as evidenced by C max (2115 ng/mL versus 1335 ng/mL) and AUC (17884 ng·h/mL versus 10328 ng·h/mL). The mean half-life was 11.1 hours in females and 7.6 hours in males. The apparent volume of distribution of metaxalone was approximately 22% higher in males than in females, but not significantly different when adjusted for body weight. Similar findings were also seen when the previously described combined dataset was used in the analysis.

    Hepatic/Renal Insufficiency:

    The impact of hepatic and renal disease on the pharmacokinetics of metaxalone has not been determined. In the absence of such information, metaxalone should be used with caution in patients with hepatic and/or renal impairment.

  • INDICATIONS AND USAGE

    Metaxalone is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions. The mode of action of this drug has not been clearly identified, but may be related to its sedative properties. Metaxalone does not directly relax tense skeletal muscles in man.

  • CONTRAINDICATIONS

    Known hypersensitivity to any components of this product.

    Known tendency to drug induced, hemolytic, or other anemias.

    Significantly impaired renal or hepatic function.

  • WARNINGS

    Metaxalone may enhance the effects of alcohol and other CNS depressants.

  • PRECAUTIONS

    Metaxalone should be administered with great care to patients with pre-existing liver damage. Serial liver function studies should be performed in these patients.

    False-positive Benedict’s tests, due to an unknown reducing substance, have been noted. A glucose-specific test will differentiate findings.

    Taking metaxalone with food may enhance general CNS depression; elderly patients may be especially susceptible to this CNS effect. (See CLINICAL PHARMACOLOGY: Pharmacokinetics and PRECAUTIONS: Information for Patients section).

    Information for Patients

    Metaxalone may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle, especially when used with alcohol or other CNS depressants.

    Drug Interactions

    The sedative effects of metaxalone and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive. Therefore, caution should be exercised with patients who take more than one of these CNS depressants simultaneously.

    Carcinogenesis, Mutagenesis, Impairment of Fertility

    The carcinogenic potential of metaxalone has not been determined.

    Pregnancy

    Reproduction studies in rats have not revealed evidence of impaired fertility or harm to the fetus due to metaxalone. Post marketing experience has not revealed evidence of fetal injury, but such experience cannot exclude the possibility of infrequent or subtle damage to the human fetus. Safe use of metaxalone has not been established with regard to possible adverse effects upon fetal development. Therefore, metaxalone tablets should not be used in women who are or may become pregnant and particularly during early pregnancy unless, in the judgement of the physician, the potential benefits outweigh the possible hazards.

    Nursing Mothers

    It is not known whether this drug is secreted in human milk. As a general rule, nursing should not be undertaken while a patient is on a drug since many drugs are excreted in human milk.

    Pediatric Use

    Safety and effectiveness in children 12 years of age and below have not been established.

  • ADVERSE REACTIONS

    The most frequent reactions to metaxalone include:

    CNS: drowsiness, dizziness, headache, and nervousness or “irritability”;

    Digestive: nausea, vomiting, gastrointestinal upset.

    Other adverse reactions are:

    Immune System: hypersensitivity reaction, rash with or without pruritus;

    Hematologic: leukopenia; hemolytic anemia;

    Hepatobiliary: jaundice.

    Though rare, anaphylactoid reactions have been reported with metaxalone.

    To report SUSPECTED ADVERSE REACTIONS, contact AvKARE, Inc at 1-855-361-3993; email drugsafety@avkare.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

  • OVERDOSAGE

    Deaths by deliberate or accidental overdose have occurred with metaxalone, particularly in combination with antidepressants, and have been reported with this class of drug in combination with alcohol.

    When determining the LD 50 in rats and mice, progressive sedation, hypnosis and finally respiratory failure were noted as the dosage increased. In dogs, no LD 50 could be determined as the higher doses produced an emetic action in 15 to 30 minutes.

    Treatment - Gastric lavage and supportive therapy. Consultation with a regional poison control center is recommended.

  • DOSAGE AND ADMINISTRATION

    The recommended dose for adults and children over 12 years of age is one 800 mg tablet three to four times a day.

  • HOW SUPPLIED

    Metaxalone is available as an 800 mg, light pink to pink, capsule shaped, scored uncoated  tablet with debossing ‘AN’ on the left side of the scoring and ‘553’ on the right side of the scoring. Other side of the tablet is plain.

    They are available as follows:

    NDC  50268-530-15          10 tablets per card, 5 cards per carton

    Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

    Manufactured for:                 

    AvKARE, Inc.

    Pulaski, TN 38478

    Mfg. Rev. 08-2014-00

    AV 01/15 (P)
    AvPAK

  • PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

    NDC 50268-530-15
    Metaxalone Tablets
    800 mg
    Rx Only
    50 Tablets (5 X 10) Unit Dose

    5026853015

    NDC 50268-530-15
    Metaxalone Tablets
    800 mg
    Rx Only
    50 Tablets (5 X 10) Unit Dose

    5026853015

    Each tablet contains:
    Metaxalone
    .......................................................... 800 mg

    DOSAGE: The recommended dose for adults and children over 12 years of age is one tablet (800 mg) three to four
    times a day.

    See package insert for prescribing information.

    Store at 20º to 25ºC (68º to 77ºF); excursions permitted to 15º to 30ºC (59º to 86ºF) [See USP Controlled Room
    Temperature].

    KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

    Manufactured for:
    AvKARE, Inc.
    Pulaski, TN 38478

    AvPAK
    A PRODUCT OF AvKARE

    Mfg. Rev. 08-2014-00        AV 01/15 (P)

    label 1
  • INGREDIENTS AND APPEARANCE
    METAXALONE 
    metaxalone tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:50268-530(NDC:65162-553)
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    METAXALONE (UNII: 1NMA9J598Y) (METAXALONE - UNII:1NMA9J598Y) METAXALONE800 mg
    Inactive Ingredients
    Ingredient NameStrength
    CALCIUM CARBONATE (UNII: H0G9379FGK)  
    FD&C RED NO. 40 (UNII: WZB9127XOA)  
    HYPROMELLOSES (UNII: 3NXW29V3WO)  
    LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    SODIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)  
    POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)  
    Product Characteristics
    Colorpink (light pink to pink) Score2 pieces
    ShapeCAPSULESize19mm
    FlavorImprint Code AN;553
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:50268-530-1550 in 1 BOX, UNIT-DOSE03/13/2015
    1NDC:50268-530-111 in 1 BLISTER PACK; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA20339903/13/2015
    Labeler - AvPAK (832926666)