1. health and fitness
2. therapy

BROUGHT
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This Special Report is
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DISCLAIMER:
This monograph is designed to
be a summary of information.
While it is detailed, it is not
an exhaustive clinical review.
Readers are strongly urged to
consult any relevant primary
literature. McMahon Publishing,
King Pharmaceuticals®, Inc.,
and the authors cannot guarantee the accuracy of the information contained herein, and the
absence of typographical errors
is not guaranteed. No liability
will be assumed for the use of
this educational review. Copyright ©2008, McMahon Publishing, 545 West 45th Street, New
York, NY 10036. Printed in the
USA. All rights reserved, including the right of reproduction, in
whole or in part, in any form.
The Use of Metaxalone
in the Treatment of
Low-Back Pain
Charles E. Argoff, MD
Professor of Neurology
Albany Medical College
Director, Comprehensive Pain Program
Albany Medical Center
Albany, New York
Introduction
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Distributed by
McMahon Publishing
Acute, painful musculoskeletal conditions,
such as low-back pain, are common clinical
problems that have traditionally been treated
with a combination of modalities, including
skeletal muscle relaxants.1,2 These acute conditions can become chronic, leading to significant suffering. In addition, they are associated
with a substantial economic burden (in terms
of medical costs, absenteeism, and presenteeism).3,4
Therapy for these conditions often is challenged by the wish or need of patients to
remain active. Many patients want to recover
from their illness quickly and be relieved of
their pain and restricted range of motion while
continuing their daily activities without experi-
encing the drowsiness or sleepiness that may
accompany certain treatments.
The pain experienced following an injury to
muscle and surrounding soft tissues reflects
the activation of nociceptors and/or sensitized central neurons.5 It is often associated
with autonomic nervous system and other
protective reflex responses that are responsible for the muscle spasm or “splinting” that
restricts the range of motion of the affected
body parts. Relieving the spasm is a key goal
of treatment that underlies in part the effectiveness of skeletal muscle relaxants in reducing the pain associated with muscle injuries
or inflammation. The degree of pain usually
correlates with the degree of tissue damage,
and resolution of the injury usually brings
relief of the experienced pain.1
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The oxazolidinone derivative muscle relaxant metaxalone
(Skelaxin®, King Pharmaceuticals®, Inc.) is indicated for the
relief of pain associated with acute musculoskeletal conditions
when used in conjunction with rest, physical therapy, and other
measures.6 The recommended dose for adults and children
older than 12 years of age is one 800-mg tablet 3 to 4 times per
day.6 It has a rapid onset of action, usually within 1 hour,7 and
is generally well tolerated. Although it has sedative properties
that may contribute to its efficacy in clinical use, the incidence
of associated sleepiness or drowsiness is low.8 In continuous
use since its approval by the Food and Drug Administration
(FDA) in 1962, metaxalone continues to be a frequently prescribed9,10 muscle relaxant because of its record of efficacy
and safety.1,8,11 This monograph reviews the pharmacology, efficacy, safety, and optimal use of metaxalone.
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Overview
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Pharmacology
Mechanism of action. Metaxalone has sedative properties
that may contribute to its efficacy; however, its mode of action
has not been clearly identified. Metaxalone does not directly
relax tense skeletal muscles and has no direct action on the
contractile mechanism of striated muscle, the motor end plate,
or the nerve fiber.6
Table 1. Metaxalone Overview6
Absorption. The pharmacokinetics of metaxalone have
been evaluated in healthy adult volunteers following singledose administration under fasted and fed conditions at doses
ranging from 400 mg to 800 mg.
The single-dose pharmacokinetic parameters of metaxalone
in 2 groups of healthy volunteers are shown in Table 2. When
metaxalone is ingested in the fasting state, the time at which
peak plasma concentrations occur (Tmax) is approximately 3.3
hours after a 400-mg dose and approximately 3.0 hours after
an 800-mg dose. After Tmax, metaxalone concentrations
decline log-linearly, with a terminal half-life (t1/2) of approximately 9.0 hours following a 400-mg dose and 8.0 hours following
an 800-mg dose.6
Doubling the dose from 400 mg to 800 mg results in a
roughly proportional increase in exposure to metaxalone, as
indicated by peak plasma concentrations (Cmax) and area
under the curve from time zero to infinity (AUC∞). Apparent total
clearance of the drug from plasma after oral administration
(CL/F) is similar for 400- and 800-mg doses. Dose proportionality at doses above 800 mg has not been studied. The
absolute bioavailability of metaxalone is not known.6
Food effects. The effect of food on metaxalone pharmacokinetics has been determined in 2 studies. The first was a randomized, 2-way, crossover study in 42 healthy volunteers who
ingested one 400-mg tablet while in the fasting state and also
following the consumption of a high-fat breakfast. The study
subjects (31 men and 11 women) ranged in age from 18 to 48
years (mean, 23.5±5.7 years). Compared with administration in
the fasting state, administration after the consumption of a highfat meal increased Cmax by 177.5%, area under the curve from
time zero to last quantifiable sample (AUC0-t) by 123.5%, and
AUC∞ by 115.4%; delayed Tmax (4.3 vs 3.3 h); and decreased t1/2
(2.4 vs 9.0 h).6
In the second food-effect study, two 400-mg tablets (800
mg) were administered to 59 healthy volunteers (37 men and
22 women) ranging in age from 18 to 50 years (mean age,
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Metaxalone (5-[(3,5- dimethylphenoxy)methyl]-2-oxazolidinone) has the empiric formula C12H15NO3 and a molecular
weight of 221.25.6 Each tablet of Skelaxin® contains 800 mg of
metaxalone and the inactive ingredients alginic acid, ammonium
calcium alginate, B-Rose Liquid, cornstarch, and magnesium
stearate. Metaxalone is a white to almost white, odorless crystalline powder freely soluble in chloroform, soluble in methanol
and 96% ethanol, but practically insoluble in ether or water.6 The
onset of action of metaxalone is usually within 1 hour.7 A summary appears in Table 1.
Pharmacokinetics
Skelaxin® Tablets (King Pharmaceuticals, Bristol, TN)
Brand name (distributor/marketer)
Available dose(s)
800 mg
Year of approval by FDA
1962
Recommended dosage
800 mg tid to qid
Indication
Adjunct to rest, physical therapy, and other measures for relief of discomfort associated with acute,
painful musculoskeletal conditions
Associated with potential for abuse?
No
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Table 2. Mean Pharmacokinetic Parameters for Metaxalone, (% CV)6
Cmax; ng/mL
Tmax; h
AUC∞; ng•h/mL
t⁄; h
CL/F; L/h
400a
983 (53)
3.3 (35)
7,479 (51)
9.0 (53)
68 (50)
800b
1,816 (43)
3.0 (39)
15,044 (46)
8.0 (58)
66 (51)
a
Subjects received one 400-mg tablet under fasted conditions (n=42).
b
Subjects received two 400-mg tablets under fasted conditions (n=59).
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2
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Dose; mg
AUC∞, area under the plasma concentration–time curve from time zero to infinity; Cmax, maximum plasma drug concentration; CL/F, apparent total clearance of the drug
from plasma after oral administration; CV, coefficient of variation; t1/2, elimination half-life; Tmax, time to reach peak plasma concentration following drug administration
2
5,000
Fasted
Fed
4,000
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Concentration, ng/mL
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2,000
0
0
2
4
6
8
10
12
Time, h
Figure. Mean concentrations of metaxalone following an 800-mg dose.6
in combination with the results from 3 other studies. Analysis
of the combined data indicated 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 3 groups
of healthy volunteers of varying age is shown in Table 3.6
The effect of gender on the pharmacokinetics of metaxalone was assessed in an open-label study in which 48 healthy
adult volunteers (24 males and 24 females) were administered
two 400-mg tablets (800 mg) under fasted conditions. It was
found that the bioavailability of metaxalone was significantly
higher in the females than in the males as evidenced by Cmax
(2,115 vs 1,335 ng/mL) and AUC∞, (17,884 vs 10,328
ng•h/mL). The mean t1/2 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 the difference was not statistically significant when the values were adjusted for body weight.6
The effect of hepatic or 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 who have hepatic and/or renal impairment.
Drug interactions with Metaxalone. Metaxalone may
enhance the effects of alcohol, barbiturates, and other CNS
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25.6±8.7 years) in the fasting state and after a high-fat breakfast. Compared with administration under fasted conditions,
administration after the consumption of a high-fat meal
increased Cmax by 193.6%, AUC0-t by 146.4%, and AUC∞ by
142.2%; delayed Tmax (4.9 vs 3.0 h); and decreased t1/2 (4.2 vs
8.0 h). Substituting one 800-mg tablet for two 400-mg tablets
produced similar food-effect results. The increase in metaxalone exposure and the reduction in half-life following administration in the fed state compared with administration in the
fasting state may be attributed to more complete absorption of
metaxalone after the consumption of a high-fat meal (Figure).6
Distribution, metabolism, and excretion. Plasma protein
binding and absolute bioavailability of metaxalone are not
known, although it is thought that the drug is extensively distributed in the tissues on the basis of its apparent volume of distribution (V/F) of about 800 L and its lipophilicity (log P=2.42).6
Metaxalone is metabolized by the liver and is excreted in the
urine as unidentified metabolites.6 Drug products that have
multiple pathways of metabolism are unlikely to be involved in
significant drug-drug interactions.12
Effects of age, gender, and hepatic or renal impairment. Age and gender affect the pharmacokinetics of metaxalone. The effects of age were determined following the single
administration of two 400-mg tablets (800 mg) under fasted and
fed conditions. The results were analyzed separately as well as
3
Table 3. Mean Pharmacokinetic Parameters Following a Single Administration of Two 400-mg Metaxalone Tablets, (%CV)6
Younger Volunteers
Age, y
n
Older Volunteers
25.6±8.7
39.3±10.8
71.5±5.0
59
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A
Fasted
Fed
Fasted
Fed
Fasted
Fed
Cmax, ng/mL
1,816
(43)
3,510
(41)
2,719
(46)
2,915
(55)
3,168
(43)
3,680
(59)
3.0
(39)
4.9
(48)
3.0
(40)
8.7
(91)
2.6
(30)
6.5
(67)
14,531
(47)
20,683
(41)
19,836
(40)
20,482
(37)
23,797
(45)
24,340
(48)
15,045
(46)
20,833
(41)
20,490
(39)
20,815
(37)
24,194
(44)
24,704
(47)
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AUC∞ , area under the plasma concentration–time curve from time zero to infinity; AUC0-t, area under the curve from time zero to the last quantifiable sample;
Cmax, maximum plasma drug concentration; CV, coefficient of variation; Tmax, time to reach peak plasma concentration following drug administration.
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Efficacy
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Several studies have established the efficacy of metaxalone.
Before the specific FDA-approved indication for metaxalone
was established, limiting use of the drug to the treatment of
acute painful conditions, researchers conducted an open-label
study of metaxalone in 50 outpatients with low-back pain and
stiffness, acute lumbosacral pain, cervical stiffness, torticollis,
arthritic pain, or parkinsonism.13 Each patient had stiffness, limited range of motion, and guarding; most patients had no
abnormal neurologic findings. The age of the patients ranged
from 20 to 80 years, with the largest number of patients in the
sixth decade of life. The duration of symptoms ranged from 1
day to 30 years (median, approximately 2 years). The dose of
metaxalone ranged from 2,400 to 4,000 mg daily (average,
3,200 mg per day).
Only 42 of the original 50 patients returned for reevaluation,
after treatment of 1 to 21 days (average, 14 days). The degree
of muscle spasm and stiffness was determined by interview,
inspection, palpation, and range of motion. Muscle spasm was
defined as a sudden, violent, involuntary contraction of a muscle or muscle group attended by pain and disruption in proper
function.13 Among the 42 patients who returned for reevaluation, results were considered excellent in 16, good in 7, fair in 6,
and poor in 13. The onset of drug action was noted to be quite
rapid. A positive therapeutic outcome, defined as excellent,
good, or fair, with metaxalone use was observed in 69% of all
patients. The greatest therapeutic effect was observed in
patients with painful spasm or stiffness of the back and leg muscles. Excluding 5 patients with arthritis, of whom only 1 had a
positive outcome (good), and 2 patients with parkinsonism, neither of whom had a positive outcome, an 80% positive outcome
was achieved with metaxalone. Two patients with low-back and
leg pain who failed to respond to metaxalone subsequently
required surgery for a herniated disk. Metaxalone was well tolerated; 6 patients had mild nausea.13
4
In addition, 2 double-blind, placebo-controlled studies, each
with an identical study design, demonstrated the therapeutic
effectiveness of metaxalone in the treatment of acute skeletal
muscle spasm. The second study was undertaken in an
attempt to reproduce the findings of the first study.11 Each of
the 2 studies enrolled 100 outpatients who had low-back pain
and discomfort associated with reflex spasm or who had acute
soft tissue injury. Excluded from the studies were patients with
neurologic impairment, herniated nucleus pulposus, marked
arthritic changes, or other structural defects for which a muscle relaxant might not be indicated. The patients received
either 800 mg of metaxalone (two 400-mg tablets of metaxalone) or matching placebo tablets 4 times daily (after each
meal and at bedtime) for 7 days.11
Patients were seen before the start of therapy and after 1
week of treatment, at which time they were evaluated for palpable muscle spasm and limited range of motion. They were rated
as follows: 4 (very severe), 3 (severe), 2 (moderate), 1 (mild), or
0 (absent). A complete blood cell count and urinalysis were
obtained at the start and end of the study. Roentgenography or
myelography was performed as indicated. At the end of the
study, patients were asked to report their impression of their status in comparison with that at the initial visit and to report any
adverse effects of the medication they had received.11
In study 1, of the 51 patients who received metaxalone, a
patient-reported marked or moderate improvement in symptomatology was observed in 32 (69.6%) of the 46 patients completing the study (Table 4). The improvement was slight in 9
patients. Five patients reported no improvement, and 5 patients
did not complete the study (outcomes were unknown because
the patients did not return for follow-up). Of the 49 patients who
received placebo, 8 showed moderate improvement in symptomatology, 9 were slightly improved, 29 were unchanged, and 3
did not return for final evaluation (outcomes were unknown
because the patients did not return for follow-up). Thus, by
comparison with the 69.6% of subjects who received active
treatment, 17.4% of the 46 placebo-treated patients who completed the course of therapy showed a medically significant
improvement and 63% were therapeutic failures.11
For each of the objectively scored outcomes—range of motion
and palpable spasm—89.1% of the patients showed improvement with metaxalone therapy. Among the patients who received
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depressants; clinicians should advise their patients of this whenever relevant.6
Dosing. The recommended dose of metaxalone for adults
and children older than 12 years of age is one 800-mg tablet 3
to 4 times per day. Safety and effectiveness in children 12
years of age and younger have not been established.6
Table 4. Metaxalone 800 mg 4 Times Daily Versus Placebo11
Study 1
Study 2
Placebo
(n=46)
Metaxalone
(n=45)
Placebo
(n=43)
Patients with marked or moderate
therapeutic response, %
69.6
17.4
75.6
27.9
Patients with improved range of
motion, %a
89.1
39.1
89.7
46.5
89.1
28.3
84.4
46.5
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Patients with improved palpable
spasm, %a
P<.01 for all comparisons of metaxalone versus placebo.
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placebo, 39.1% had improved range of motion and 28.3% had
improved palpable spasm. All differences between metaxalone
and placebo were statistically significant (P<.01).11
The proportions of patients in study 2 who had a marked or
moderate therapeutic response and improvement in range of
motion and palpable spasm in response to metaxalone and
placebo are shown in Table 4. The close correlation between
the results of study 1 and study 2 indicates that the results
observed in each study were reliable measurements of the clinical effects of metaxalone.
In the 2 studies combined, the patients who were available for
7-day follow-up included 91 who received metaxalone and 89
who received placebo. In the metaxalone and placebo groups,
improved range of motion was observed in 87.9% and 42.7%,
respectively, and improved palpable spasm was observed in
86.8% and 37.1% of patients, respectively. Improvements in the
placebo group were ascribed by the investigator to expected
spontaneous improvement over 7 days. Differences between the
objective assessments of the status of patients treated with
metaxalone and those of the patients given placebo were
ascribed to the pharmacologic action of metaxalone.11
None of the patients treated with metaxalone or placebo
reported sedation as a side effect. Among the patients who
received placebo, 1 reported heartburn and 1 nausea; hypertension was observed in 1. Among the patients who received
metaxalone, 3 reported nausea and vomiting, 3 dizziness, 1
indigestion and nervousness, 1 polyuria, and 1 headache and
intensification of muscle cramps. Most patients’ complete blood
cell count and urinalysis values remained within normal limits;
white blood cell counts for 2 patients receiving metaxalone
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were 4,600 and 3,500/mcL, respectively, and for 1 patient
receiving placebo it was 3,050/mcL (normal range, 4,50010,000/mcL).11
Another double-blind placebo-controlled study also demonstrated that metaxalone is effective in treating acute involuntary
muscle spasm and associated discomfort and disability in
adults.8 This was a study of the effectiveness and tolerability of
metaxalone in 228 adult patients with painful, involuntary, localized skeletal muscle spasm of either traumatic or inflammatory
origin. Individual physicians contributed from 8 to 18 patients
to this multicenter study. The starting and most common dose
of metaxalone was two 400-mg tablets of (800 mg); matching
placebo was administered 4 times per day. The dose could be
reduced if side effects interfered with therapy. Treatment continued for 7 to 9 days in a non-crossover design.
Entrance criteria included continuous muscle spasm present for no more than 14 days, with both muscle spasm and
local pain or tenderness of at least moderate severity. Excluded from the study were patients with muscle spasm due to a
CNS disorder or to miscellaneous causes (eg, insect venom,
drug reaction, metabolic disorders) or with conditions for which
metaxalone is contraindicated (ie, severely impaired kidney or
liver function and known tendency to drug-induced, hemolytic,
or other anemias). During the 48 hours preceding the study, the
only treatments allowed were analgesics on an as-needed
basis, physiotherapy, and rest. During the first 48 hours of the
study, treatment was limited to the study tablets without physiotherapy, although supplementary analgesics and limited physiotherapy were permitted at patient request. Bedtime hypnotics,
physiotherapy, and analgesics were permitted following the first
Table 5. Investigators’ Rating of Improvements8
48 Hours
Variable
Final Evaluation
Patients Improved, %
Patients Improved, %
Placebo
(n=86)
P value
Metaxalone
(n=78)
Placebo
(n=71)
P value
Muscle spasm
73.3
54.7
<.01
92.3
77.5
<.025
Interference with daily activities
67.8
47.7
<.01
88.5
74.6
<.05
Local pain or tenderness over area
of spasm
68.9
57.0
NS
91.0
76.1
<.025
Limitation of normal motion
63.3
51.2
NS
88.5
73.2
<.0025
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NS, not statistically significant.
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48 hours at an investigator’s discretion. Alcoholic beverages,
tranquilizers, sedatives, muscle relaxants other than metaxalone, and anti-inflammatory drugs other than aspirin (dose
unspecified) were excluded during the entire study.8
Evaluations were made before treatment, after 48 hours, and
at the end of the study at days 7, 8, or 9. Objective evaluation
was based on 4 criteria: degree of muscle spasm, degree of
local pain or tenderness over the area of spasm, limitation of normal motion, and interference with activities. Each criterion was
evaluated on a 5-point scale: 0 (absent), 1 (mild), 2 (moderate),
3 (severe), or 4 (very severe). Patients and investigators rated
outcome subjectively as recovered, much better, better, same, or
worse. End-of-study data were excluded from the analysis if
patients had discontinued their medication for any reason other
than improvement or treatment failure. Data from 52 patients
were initially unacceptable or subsequently failed to meet the
protocol requirements of the first 48 hours, and additional
patients’ data had to be eliminated from the final evaluations.8
For every objective parameter evaluated by the investigators—muscle spasm, interference with daily activities, local pain
or tenderness over area of spasm, and limitation of normal
motion—a substantially greater improvement was observed in
the metaxalone group than in the placebo group at both 48
hours and study end, with all differences between metaxalone
and placebo reaching statistical significance except for local
pain or tenderness over area of spasm and limitation of normal
motion at 48 hours (Table 5).8
Based on both the investigator and patient global assessments, 74.4% and 85.9% of patients on metaxalone recovered,
felt much better, or felt better, respectively, at the 48-hour and
final evaluations. Values for metaxalone relative to placebo for
investigators at 48-hour evaluations and for patients at final
evaluations were statistically significant (P<.025 and P<.01,
respectively). They were of borderline statistical significance
(P<.10) for investigators at final evaluations and for patients at
48-hour evaluations. Adverse effects in both groups were clinically insignificant.8
The findings in the placebo group in this study reflect the
spontaneous improvement that is to be expected in the type of
muscle spasm studied. However, metaxalone significantly
enhanced this response with respect to all 4 variables when
they were evaluated at 7 to 9 days and with respect to muscle
spasm and interference with daily activities at 48 hours, supporting the view that metaxalone can improve patients’
chances of responding to treatment relatively quickly. This is
important, because patients in general are eager to obtain
rapid relief of muscle spasm and pain and improvement of
mobility and to return quickly to normal activities. When asked
whether they would like to take the same drug if they experienced a new episode of a similar condition, 76% of the patients
in this study who received metaxalone replied affirmatively.8
Another double-blind placebo-controlled study of metaxalone was conducted in 100 patients selected from industrial
and general medical practice offices.14 Patients had skeletal
muscle symptoms of muscle spasm, pain, tenderness, and
restriction of motion of acute onset, and their diagnoses included traumatic sprains or strains, whiplash injuries, and
fibromyositis, among others. Patients were randomized to
receive 800 mg of metaxalone 4 times per day (n=50) or
matching placebo (n=50) for 10 days. All other medication was
to be stopped during the trial. Symptoms and signs of muscle
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Safety Profile
Metaxalone is a nonopioid without any known risk for addiction when taken as prescribed and presents no known risk for
dependence. It may be stopped without fear of withdrawal
symptoms.6 Furthermore, it has no adverse cardiovascular
effects, does not produce dry mouth, urinary retention, or
blurred vision, and does not interact with monoamine oxidase
inhibitors. Like all prescription medicines, metaxalone causes
adverse effects that need to be recognized and monitored
when it is prescribed; however, in Dent et al only 4 of 115
patients reported sedation-related adverse effects.8 Taking
metaxalone with food may enhance general CNS depression,
especially in elderly patients. The most frequent reactions are
nausea, vomiting, gastrointestinal upset, drowsiness, dizziness,
headache, and nervousness or “irritability.”
Metaxalone is contraindicated for any person who has a
known hypersensitivity to any components of the product, a
known tendency to drug-induced hemolytic or other anemia, or
significantly impaired renal or hepatic function. Patients should
be warned that metaxalone may impair mental and/or physical
abilities required for the performance of hazardous tasks, such
as operating machinery and driving a motor vehicle. The potential danger is especially great when metaxalone is used with
alcohol or other CNS depressants whose effects may be
enhanced by metaxalone.6 Metaxalone should be administered
with great care to patients with preexisting liver damage, and
serial liver function studies should be performed in these
patients; the drug is contraindicated in patients with significantly
impaired hepatic or renal function.6 The safety and effectiveness
of metaxalone in children 12 years of age and younger have not
been established. Deaths by deliberate or accidental overdose
have occurred with metaxalone, particularly when it is used in
combination with antidepressants and alcohol.6,15-17
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spasm were recorded at the start of the trial and reevaluated
after 5 and 10 days. Patients ranged in age from 16 to 89 years.
Response of muscle spasm to treatment was evaluated as
excellent (complete disappearance), good (substantial relief),
fair (minimal relief), unchanged, or worse. Response of pain to
treatment was evaluated as completely relieved, partially
relieved, or unaffected.14
An excellent or good response of muscle spasm was
observed in 52% of patients in the metaxalone group and 46%
of patients in the placebo group. No patients had worse spasm
after treatment. Complete or partial relief of pain was experienced by 66% of patients on metaxalone therapy and 72% of
patients on placebo. This high rate of response to placebo is
noteworthy because patients were not to have been taking
analgesics. None of the differences in response to therapy
were of statistical significance. Spontaneous relief of spasm is
expected in the types of skeletal muscle disorders treated in
this study population. The only side effects encountered in this
study were vomiting and nausea.14
The report of this study did not indicate the proportion of
patients who were being treated for industrial accidents; this
may have been a factor contributing to the relatively low rate of
response of spasm to active or placebo treatment within 10
days. In this study, the relief of muscle spasm in 46% of patients
receiving placebo showed an excellent or good response. In a
study previously described, the muscle spasm of 77.5% of
patients receiving placebo improved within 7 to 9 days.8
Guideline Recommendations
A
Koes et al18 reviewed clinical guidelines from 11 different
countries published between 1994 and 2000. The authors found
the guidelines to be similar with regard to diagnostic classification (triage) and the recommended use of diagnostic and therapeutic interventions. All of the guidelines emphasized the early
and gradual activation of patients and discouraged prescribed
bed rest. All guidelines also highlighted the importance of
psychosocial factors as risk factors for chronic musculoskeletal
pain; however, many differed in their recommendation for muscle relaxant therapy.18
The current American College of Physicians and the American Pain Society guidelines, published in 2007, include 7 recommendations for the diagnosis and treatment of low-back
pain. With regard to the treatment of low-back pain only, the
guidelines recommend the following19:
• Clinicians conduct a focused history (including assessment of psychosocial risk factors, which predict risk for
chronic disabling back pain) and physical examination
to categorize low-back pain as follows: nonspecific lowback pain, back pain potentially associated with radiculopathy or spinal stenosis, or back pain potentially
associated with another specific spinal cause
• Clinicians consider the use of medications with proven
benefits in conjunction with back care information and
self-care. Clinicians should assess the severity of baseline pain and functional deficits, the potential benefits
and risks of therapy, and the relative lack of long-term
efficacy and safety data before initiating therapy
• Clinicians consider the addition of nonpharmacologic
therapy with proven benefits for patients who do not
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improve with selfcare options. Options include: for acute
low-back pain—spinal manipulation; for chronic or subacute low-back pain—intensive interdisciplinary rehabilitation, exercise therapy, acupuncture, massage therapy,
spinal manipulation, yoga, cognitive-behavioral therapy, or
progressive relaxation
From a practical standpoint, the ready availability of
nonprescription analgesic agents, including acetaminophen
and nonsteroidal anti-inflammatory drugs, makes it likely that
many patients with an acute painful musculoskeletal condition
will use 1 or more of these analgesics for pain relief before
consulting a physician and even after consulting a physician
and receiving a prescription for a skeletal muscle relaxant.
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Conclusion
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Metaxalone is an effective and well-tolerated skeletal
muscle relaxant that has remained commonly prescribed
since 1962.
Double-blind placebo-controlled clinical trials have demonstrated the effectiveness of metaxalone compared with placebo in helping to rapidly relieve the symptoms and signs of
acute musculoskeletal conditions, including pain, tenderness, limitation of normal motion, palpable spasm, and interference with daily activities (Table 6).8,11 In most cases,
adverse effects were tolerable, with drowsiness, a common
concern with muscle relaxants, was found in only 4 of 115
patients in 1 study.8 Based on these clinical findings,
Skelaxin® (metaxalone) continues to be a widely prescribed
agent for low-back pain that can provide prompt, effective
relief of symptoms with minimal sedation.8,9
Table 6. Summary of Metaxalone Placebo-Controlled Clinical Trials
Year
Dent8
1975
Diamond14
1966
Fathie11—first group
1964
Fathie11—second group
1964
Population
Number Enrolled
Main Outcomes
Acute skeletal muscle
disorders (various
locations; not specified)
228
Metaxolone effective for muscle
spasm, local pain, limitation of
normal motion, and interference
with daily activities using 5-point
scale.
Muscle pain and spasm,
unspecified locations
100
No significant difference using
5-point scale for muscle spasm or
4-point scale for pain.
Low-back pain
100
Metaxolone effective for global
therapeutic response using
4-point scale, range of motion
using 5-point scale, and palpable
spasm using 5-point scale.
Low-back pain
100
Metaxolone effective for global
therapeutic response using
4-point scale, range of motion
using 5-point scale, and palpable
spasm using 5-point scale.
te
Lead Author
d.
Adapted from references 8,11,and 14.
7
References
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back pain: a review of carisoprodol, cyclobenzaprine hydrochloride, and
metaxalone. Clin Ther. 2004;26(9):1355-1367
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12. Applications of Pharmacokinetic Principles in Drug Development. Krishna,
Rajesh (editor). Kluwer Academic/Plenum Publishers. New York, NY. 2003.
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14. Diamond S. Double-blind study of metaxalone; use as skeletal-muscle relaxant. JAMA. 1966;195(6):479-480.
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15. Gruszecki AC, Kloda S, Simmons GT, Daly TM, Hardy RW, Robinson CA.
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6. Skelaxin® [package insert]. Bristol, TN: King Pharmaceuticals, Inc; 2007.
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19. Chou R, Qaseem A, Snow V, et al. Diagnosis and treatment of low back pain:
a joint clinical practice guideline from the American College of Physicians and
the American Pain Society. Ann Intern Med. 2007;147(7):478-491.
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9. Harden RN, Argoff C. A review of three commonly prescribed skeletal muscle
relaxants. J Back Musculoskeletal Rehab. 2000;15(2-3):63-66.
18. Koes BW, van Tulder MW, Ostelo R, Kim Burton A, Waddell G. Clinical guidelines for the management of low back pain in primary care: an international
comparison. Spine. 2001;26(22):2504-2513.
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3. FrymoyerJW, Cats-Baril LW. An overview of the incidences and cost of low
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11. Fathie K. A second look at a skeletal muscle relaxant: a double-blind study of
metaxalone. Curr Ther Res Clin Exp. 1964;6:677-683.
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