Label: METAXALONE- metaxalone tablet

  • NDC Code(s): 0185-0448-01, 0185-0448-10
  • Packager: Eon Labs, Inc.
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated August 24, 2016

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  • Rx only
  • DESCRIPTION

    Metaxalone tablets, USP are available as an 800 mg tablet.

    Chemically, metaxalone is 5-[(3,5-dimethylphenoxy)methyl]-2-oxazolidinone. The empirical formula is C12H15NO3, 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: corn starch, alginic acid, acacia, sodium starch glycolate, magnesium stearate and FD&C red No. 40 aluminum lake.

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  • 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 tablets 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 tablets from 400 mg to 800 mg results in a roughly proportional increase in metaxalone exposure as indicated by peak plasma concentrations (Cmax) 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
    *
    Subjects received 1x400 mg tablet under fasted conditions (N=42)
    Subjects received 2x400 mg tablets under fasted conditions (N=59)

    Dose (mg)

    Cmax (ng/mL)

    Tmax (h)

    AUC∞ (ng●h/mL)

    T1/2 (h)

    CL/F (L/h)

    400*

    983 (53)

    3.3 (35)

    7479 (51)

    9.0 (53)

    68 (50)

    800

    1816 (43)

    3.0 (39)

    15044 (46)

    8.0 (58)

    66 (51)

    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 Cmax by 177.5% and increased AUC (AUC0-t, AUC∞) by 123.5% and 115.4%, respectively. Time-to-peak concentration (Tmax) 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 Cmax by 193.6% and increased AUC (AUC0-t, AUC∞) by 146.4% and 142.2%, respectively. Time-to-peak concentration (Tmax) 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. Mean (SD) Concentrations of Metaxalone Following an 800 mg Dose Under Fasted and Fed Conditions

    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, CPY2E1, 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) Pharmacokinetics 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

    Cmax

    (ng/mL)

    1816

    3510

    2719

    2915

    3168

    3680

    (43)

    (41)

    (46)

    (55)

    (43)

    (59)

    Tmax (h)

    3.0

    4.9

    3.0

    8.7

    2.6

    6.5

    (39)

    (48)

    (40)

    (91)

    (30)

    (67)

    AUC0-t

    (ng·h/mL)

    14531

    20683

    19836

    20482

    23797

    24340

    (47)

    (41)

    (40)

    (37)

    (45)

    (48)

    AUC∞

    (ng·h/mL)

    15045

    20833

    20490

    20815

    24194

    24704

    (46)

    (41)

    (39)

    (37)

    (44)

    (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 Cmax (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 tablets should be used with caution in patients with hepatic and/or renal impairment.

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  • INDICATIONS AND USAGE

    Metaxalone tablets are 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.

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  • CONTRAINDICATIONS

    Known hypersensitivity to any components of this product.

    Known tendency to drug induced, hemolytic or other anemias.

    Significantly impaired renal or hepatic function.

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  • WARNINGS

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

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  • 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 tablets 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).

    Information for Patients

    Metaxalone tablets 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 tablets 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.

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  • 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.

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  • 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 LD50 in rats and mice, progressive sedation, hypnosis and finally respiratory failure were noted as the dosage increased. In dogs, no LD50 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.

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  • 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.

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  • HOW SUPPLIED

    Metaxalone Tablets, USP, for oral administration, are available as

    800 mg

    Rose-colored, capsule-shaped tablets, debossed “E 448” on one side and scored on the other side and supplied as:

    NDC 0185-0448-01 bottles of 100

    NDC 0185-0448-10 bottles of 1000

    Dispense contents in a tight, light-resistant container as defined in the USP with a child-resistant closure, as required.

    Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

    KEEP TIGHTLY CLOSED.

    To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    Manufactured by Sandoz Inc., Princeton, NJ 08540

    Rev. May 2016

    46188486

    MF0448REV05/16

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  • Metaxalone 800 mg x 100 Tablets, USP - Label

    NDC 0185-0448-01

    Metaxalone Tablets, USP

    800 mg

    Rx only

    100 Tablets

    Sandoz

    800 mg x 100 Tablets
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  • INGREDIENTS AND APPEARANCE
    METAXALONE 
    metaxalone tablet
    Product Information
    Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0185-0448
    Route of Administration ORAL
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    METAXALONE (UNII: 1NMA9J598Y) (METAXALONE - UNII:1NMA9J598Y) METAXALONE 800 mg
    Inactive Ingredients
    Ingredient Name Strength
    ACACIA (UNII: 5C5403N26O)  
    ALGINIC ACID (UNII: 8C3Z4148WZ)  
    STARCH, CORN (UNII: O8232NY3SJ)  
    FD&C RED NO. 40 (UNII: WZB9127XOA)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    Product Characteristics
    Color PINK (rose-colored) Score 2 pieces
    Shape CAPSULE Size 19mm
    Flavor Imprint Code E448
    Contains     
    Packaging
    # Item Code Package Description Marketing Start Date Marketing End Date
    1 NDC:0185-0448-10 1000 in 1 BOTTLE; Type 0: Not a Combination Product 03/31/2010
    2 NDC:0185-0448-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 03/31/2010
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    ANDA ANDA040445 03/31/2010
    Labeler - Eon Labs, Inc. (012656273)
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