METAXALONE - metaxalone tablet

United States - English - NLM (National Library of Medicine)

Buy It Now

Active ingredient:
METAXALONE (UNII: 1NMA9J598Y) (METAXALONE - UNII:1NMA9J598Y)
Available from:
Keltman Pharmaceuticals Inc.
INN (International Name):
METAXALONE
Composition:
METAXALONE 800 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
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. 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.
Product summary:
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: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Rx Only . Manufactured and Distributed by: Corepharma LLC Middlesex, NJ 08846 This Product was Repackaged By Sandhills Packaging for: Keltman Pharmaceuticals Inc. 1 Lakeland Square, Suite A Flowood, MS 39232 United States
Authorization status:
Abbreviated New Drug Application
Authorization number:
68387-108-30, 68387-108-60, 68387-108-90

METAXALONE - metaxalone tablet

Keltman Pharmaceuticals Inc.

----------

Metaxalone Tablets, 800 mg

DESCRIPTION

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.

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.

Abs orption

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

Parameters

Dos e

(mg)

C

(ng/mL)

T

(h)

AUC∞

(ng h/mL)

T

(h)

CL/F

(L/h)

983 (53)

3.3 (35)

7479 (51)

9.0 (53)

68 (50)

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 C

177.5% and increased AUC (AUC0-t, AUC∞) by 123.5% and 115.4%, respectively. Time-to-peak

concentration (T

) 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

Fed Conditions

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)

max

max

1/2

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

Fas ted

Fed

Fas ted

Fed

Fas ted

Fed

C

(ng/mL)

1816

3510

2719

2915

3168

3680

(43)

(41)

(46)

(55)

(43)

(59)

T

(h)

(39)

(48)

(40)

(91)

(30)

(67)

AUC

(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 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.

Hepatic/Renal Insufficiency

max

max

0 -t

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.

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 tablets 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 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.

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.

DRUG ABUSE AND DEPENDENCE

Overdos age

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.

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 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:

Source

Prod.

NDC

Strength

Quantity/Form

Color

Code

68387-108-

800 mg

30 Tablets in a Plastic

Bottle

PINK

64720-321

68387-108-

800 mg

60 Tablets in a Plastic

Bottle

PINK

64720-321

68387-108-

800 mg

90 Tablets in a Plastic

Bottle

PINK

64720-321

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

Rx Only.

Manufactured and Distributed by:

Corepharma LLC

Middlesex, NJ 08846

This Product was Repackaged By Sandhills Packaging for:

Keltman Pharmaceuticals Inc.

1 Lakeland Square, Suite A

Flowood, MS 39232

United States

Metaxalone 800 mg Label

METAXALONE

metaxalone tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 8 38 7-10 8 (NDC:6 4720 -321)

Route of Administration

ORAL

Keltman Pharmaceuticals Inc.

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

METAXALO NE (UNII: 1NMA9 J59 8 Y) (METAXALONE - UNII:1NMA9 J59 8 Y)

METAXALONE

8 0 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

ALGINIC ACID (UNII: 8 C3Z4148 WZ)

STARCH, CO RN (UNII: O8 232NY3SJ)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

Product Characteristics

Color

PINK

S core

no sco re

S hap e

CAPSULE (Co nvex)

S iz e

19 mm

Flavor

Imprint Code

M;58 ;59

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 8 38 7-10 8 -30

30 in 1 BOTTLE, PLASTIC

2

NDC:6 8 38 7-10 8 -6 0

6 0 in 1 BOTTLE, PLASTIC

3

NDC:6 8 38 7-10 8 -9 0

9 0 in 1 BOTTLE, PLASTIC

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 40 48 6

0 6 /25/20 0 8

Labeler -

Keltman Pharmaceuticals Inc. (362861077)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Sandhills Packaging

8 25138 717

re pa c k

Revised: 9/2010

Similar products

Search alerts related to this product

Share this information