United States - English - NLM (National Library of Medicine)
METAXALONE - metaxalone tablet
Keltman Pharmaceuticals Inc.
Metaxalone Tablets, 800 mg
Metaxalone tablets are available as an 800 mg tablet.
Chemically, metaxalone is 5-[(3,5-dimethylphenoxy)methyl]-2-oxazolidinone. The empirical formula is
H1 NO , which corresponds to a molecular weight of 221.25. The structural formula is:
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: alginic acid, ammonium
calcium alginate, B-Rose Liquid, corn starch and magnesium stearate.
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.
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
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
) 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
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
177.5% and increased AUC (AUC0-t, AUC∞) by 123.5% and 115.4%, respectively. Time-to-peak
) 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
by 193.6% and increased AUC (AUC
, AUC∞) by 146.4% and
142.2%, respectively. Time-to-peak concentration (T
) 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
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
Subjects received 1×4 00mg tablet under fasted conditions (N=4 2)
Subjects received 2×4 00 mg tablets under fasted conditions (N=59)
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
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
25.6 ± 8.7
39.3 ± 10.8
71.5 ± 5.0
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
(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.
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.
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.
Known hypersensitivity to any components of this product.
Known tendency to drug induced, hemolytic or other anemias.
Significantly impaired renal or hepatic function.
Metaxalone tablets may enhance the effects of alcohol and other CNS depressants.
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.
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.
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
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.
Safety and effectiveness in children 12 years of age and below have not been established.
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;
Though rare, anaphylactoid reactions have been reported with metaxalone.
DRUG ABUSE AND DEPENDENCE
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 in rats and mice, progressive sedation, hypnosis and finally respiratory
failure were noted as the dosage increased. In dogs, no LD could be determined as the higher doses
produced an emetic action in 15 to 30 minutes.
Gastric lavage and supportive therapy. Consultation with a regional poison control center is
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.
Metaxalone Tablets are available as an 800mg oval, convex, pink tablet with one side debossed “M” and
the other side and scored on the other side debossed "58/59".
They are supplied by Keltman Pharmaceuticals Inc. as follows:
30 Tablets in a Plastic
60 Tablets in a Plastic
90 Tablets in a Plastic
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Manufactured and Distributed by:
Middlesex, NJ 08846
This Product was Repackaged By Sandhills Packaging for:
Keltman Pharmaceuticals Inc.
1 Lakeland Square, Suite A
Flowood, MS 39232
Metaxalone 800 mg Label
Product T ype
HUMAN PRESCRIPTION DRUG
Ite m Code (Source )
NDC:6 8 38 7-10 8 (NDC:6 4720 -321)
Route of Administration
Keltman Pharmaceuticals Inc.
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
METAXALO NE (UNII: 1NMA9 J59 8 Y) (METAXALONE - UNII:1NMA9 J59 8 Y)
8 0 0 mg
Stre ng th
ALGINIC ACID (UNII: 8 C3Z4148 WZ)
STARCH, CO RN (UNII: O8 232NY3SJ)
MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )
no sco re
S hap e
CAPSULE (Co nvex)
S iz e
Marketing Start Date
Marketing End Date
NDC:6 8 38 7-10 8 -30
30 in 1 BOTTLE, PLASTIC
NDC:6 8 38 7-10 8 -6 0
6 0 in 1 BOTTLE, PLASTIC
NDC:6 8 38 7-10 8 -9 0
9 0 in 1 BOTTLE, PLASTIC
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
ANDA0 40 48 6
0 6 /25/20 0 8
Keltman Pharmaceuticals Inc. (362861077)
Ad d re s s
Busine ss Ope rations
8 25138 717
re pa c k