METAXALONE- metaxalone tablet

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

Buy It Now

Active ingredient:
METAXALONE (UNII: 1NMA9J598Y) (METAXALONE - UNII:1NMA9J598Y)
Available from:
A-S Medication Solutions
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
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. Known hypersensitivity to any components of this product. Known tendency to drug induced, hemolytic, or other anemias. Significantly impaired renal or hepatic function.
Product summary:
Product: 50090-4448 NDC: 50090-4448-0 30 TABLET in a BOTTLE NDC: 50090-4448-1 60 TABLET in a BOTTLE NDC: 50090-4448-2 15 TABLET in a BOTTLE NDC: 50090-4448-3 20 TABLET in a BOTTLE NDC: 50090-4448-4 10 TABLET in a BOTTLE NDC: 50090-4448-5 100 TABLET in a BOTTLE
Authorization status:
Abbreviated New Drug Application
Authorization number:
50090-4448-0, 50090-4448-1, 50090-4448-2, 50090-4448-3, 50090-4448-4, 50090-4448-5

METAXALONE- metaxalone tablet

A-S Medication Solutions

----------

METAXALONE TABLETS, USP

DESCRIPTION

Metaxalone Tablets, USP are available as an 800 mg, capsule shaped, scored pink tablet. Chemically,

metaxalone, USP is 5-[(3,5-dimethylphenoxy)methyl]-2-oxazolidinone. The empirical formula is

H NO , which corresponds to a molecular weight of 221.25. The structural formula is:

Metaxalone, USP is a white to almost white, crystalline powder freely soluble in dichloromethane,

soluble in methanol, sparingly soluble in ethanol and ethyl acetate, slightly soluble in toluene and

isopropanol, insoluble in water and n-hexane.

Each tablet contains 800 mg metaxalone, USP and the following inactive ingredients: alginic acid, corn

starch, ferric oxide red, copovidone, magnesium stearate, povidone, pregelatinized starch, sodium

alginate.

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 (CNS) 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

) 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

Table 1: Mean (%CV) Metaxalone Pharmacokinetic Parameters

Dose (mg)

C

(ng/mL)

T

AUC

(ng h/mL)

t

CL/F

(L/h)

983 (53)

3.3 (35)

7,479 (51)

9.0 (53)

68 (50)

1,816 (43)

3.0 (39)

15,044 (46)

8.0 (58)

66 (51)

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

Subjects 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

by 177.5%

and increased AUC (AUC

AUC ) by 123.5% and 115.4%, respectively. Time-to-peak concentration

) 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).

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.

max

max

1/2

0-t,

0-t,

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

Food

Fasted

Fasted

Fasted

C

(ng/mL)

1,816

(43)

3,510

(41)

2,719

(46)

2,915

(55)

3,168

(43)

3,680

(59)

T

(39)

(48)

(40)

(91)

(30)

(67)

AUC

(ngh/mL)

14,531

(47)

20,683

(41)

19,836

(40)

20,482

(37)

23,797

(45)

24,340

(48)

AUC

(ngh/mL)

15,045

(46)

20,833

(41)

20,490

(39)

20,815

(37)

24,194

(44)

24,704

(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

(2,115 ng/mL versus 1,335 ng/mL) and AUC (17,884

ngh/mL versus 10,328 ngh/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.

max

max

0 -t

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

Serotonin Syndrome

Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during

concomitant use of serotonergic drugs with metaxalone used within the recommended dosage range

(see PRECAUTIONS: Drug Interactions) and with metaxalone as a single agent taken at doses higher

than the recommended dose (see OVERDOSAGE). Serotonergic drugs include selective serotonin

reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic

antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, opioids (particularly fentanyl, meperidine,

and methadone), drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone,

tramadol), and drugs that impair metabolism of serotonin (including monoamine oxidase (MAO)

inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and

intravenous methylene blue) (see PRECAUTIONS: Drug Interactions).

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma),

autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations

(e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting,

diarrhea). The onset of symptoms generally occurs within several hours to a few days, but may occur

later than that. Discontinue metaxalone if serotonin syndrome is suspected.

Risks from Concomitant Use with Alcohol or other CNS Depressants

The sedative effects of metaxalone and other CNS depressants (e.g., alcohol, benzodiazepines, opioids,

tricyclic antidepressants (TCAs)) may be additive. Exercise caution with patients who take more than

one of these CNS depressants simultaneously. Follow patients closely for signs and symptoms of

respiratory depression and sedation (see PRECAUTIONS: Drug Interactions).

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).

Information for Patients

Driving or Operating Heavy Machinery:

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.

Serotonin Syndrome:

Inform patients that metaxalone could cause a rare but potentially life-threatening condition resulting

from administration of doses higher than the recommended dose or from concomitant administration of

serotonergic drugs with metaxalone used within the recommended dosage range. Warn patients of the

symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct

patients to inform their healthcare providers if they are taking, or plan to take, serotonergic medications

(see WARNINGS, PRECAUTIONS: Drug Interactions, and OVERDOSAGE).

Drug Interactions

CNS Depressants:

The sedative effects of metaxalone and other CNS depressants (e.g., alcohol, benzodiazepines, opioids,

tricyclic antidepressants (TCAs)) may be additive. Exercise caution with patients who take more than

one of these CNS depressants simultaneously. Follow patients closely for signs and symptoms of

respiratory depression and sedation (see WARNINGS).

Serotonergic Drugs:

Serotonin syndrome has resulted from concomitant use of serotonergic drugs with metaxalone used

within the recommended dosage range (see WARNINGS). If concomitant use is warranted, carefully

observe the patient, particularly during treatment initiation and dose adjustment. Discontinue metaxalone

if serotonin syndrome is suspected.

Examples of serotonergic drugs include: selective serotonin reuptake inhibitors (SSRIs), serotonin and

norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor

antagonists, opioids (particularly fentanyl, meperidine, and methadone), drugs that affect the serotonin

neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors

(those intended to treat psychiatric disorders and also others, such as linezolid and intravenous

methylene blue).

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: anaphylaxis, hypersensitivity reaction, rash with or without pruritus;

Hematologic: leukopenia; hemolytic anemia;

Hepatobiliary: jaundice.

CNS: cases of serotonin syndrome, a potentially life-threatening condition, have been reported during

concomitant use of serotonergic drugs with metaxalone used within the recommended dosage range and

with metaxalone as a single agent taken at doses higher than the recommended dose (see WARNINGS,

PRECAUTIONS: Drug Interactions, and OVERDOSAGE).

To report SUSPECTED ADVERSE REACTIONS, contact Dr.Reddy’s Laboratories, Inc., at 1-

888-375-3784 or FDA at 1-800-FDA-1088 or http://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.

Serotonin syndrome has been reported when metaxalone was used at doses higher than the

recommended dose (see WARNINGS and ADVERSE REACTIONS).

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

Product: 50090-4448

NDC: 50090-4448-0 30 TABLET in a BOTTLE

NDC: 50090-4448-1 60 TABLET in a BOTTLE

NDC: 50090-4448-2 15 TABLET in a BOTTLE

NDC: 50090-4448-3 20 TABLET in a BOTTLE

NDC: 50090-4448-4 10 TABLET in a BOTTLE

NDC: 50090-4448-5 100 TABLET in a BOTTLE

Storage

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]. Dispense in well-closed, light-resistant containers. Manufactured by:

ScieGen Pharmaceuticals, Inc. Hauppauge, NY 11788, USA

Metaxalone

METAXALONE

metaxalone tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:50 0 9 0 -4448 (NDC:55111-6 50 )

Route of Administration

ORAL

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)

FERRIC O XIDE RED (UNII: 1K0 9 F3G6 75)

CO PO VIDO NE K2 5-3 1 (UNII: D9 C330 MD8 B)

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

PO VIDO NE, UNSPECIFIED (UNII: FZ9 8 9 GH9 4E)

SO DIUM ALGINATE (UNII: C26 9 C4G2ZQ)

Product Characteristics

Color

PINK

S core

2 pieces

S hap e

OVAL

S iz e

19 mm

Flavor

Imprint Code

SG;323

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

A-S Medication Solutions

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:50 0 9 0 -4448 -0

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /0 5/20 19

2

NDC:50 0 9 0 -4448 -1

6 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /0 5/20 19

3

NDC:50 0 9 0 -4448 -2

15 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /0 5/20 19

4

NDC:50 0 9 0 -4448 -3

20 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /0 5/20 19

5

NDC:50 0 9 0 -4448 -4

10 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /0 5/20 19

6

NDC:50 0 9 0 -4448 -5

10 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /20 /20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 746 6

0 8 /31/20 17

Labeler -

A-S Medication Solutions (830016429)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

A-S Medicatio n So lutio ns

8 30 0 16 429

RELABEL(50 0 9 0 -4448 ) , REPACK(50 0 9 0 -4448 )

Revised: 8/2019

Similar products

Search alerts related to this product

View documents history

Share this information