Metaxalone

Dosage and Administration ( 2 ) 06/2024

1 INDICATIONS AND USAGE Metaxalone Tablets, 640 mg, are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions in adults and pediatric patients 13 years of age and older. Metaxalone Tablets, 640 mg, is a muscle relaxant, indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions in adult and pediatric patients 13 years of age and older. ( 1 )

2 DOSAGE AND ADMINISTRATION The recommended dosage of Metaxalone Tablets, 640 mg in adults and pediatric patients 13 years of age and older is 640 mg taken orally with or without food, three to four times a day. The maximum recommended daily dosage is 2,560 mg (one tablet four times a day). Metaxalone Tablets, 640 mg and SKELAXIN 800 mg are not mutually substitutable on a mg-to-mg basis due to differences in pharmacokinetic profiles [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ]. When it is appropriate to switch a patient taking SKELAXIN 800 mg on an empty stomach to Metaxalone Tablets, 640 mg: Stop SKELAXIN 800 mg three times a day and start Metaxalone Tablets 640 mg three times a day on an empty stomach, OR Stop SKELAXIN 800 mg four times a day and start Metaxalone Tablets 640 mg four times a day on an empty stomach. For patients who have been taking either product with food, do not switch between SKELAXIN 800 mg and Metaxalone Tablets, 640 mg. Recommended dosage in adults and pediatric patients 13 years of age and older is 640 mg taken orally, with or without food, three to four times a day ( 2 ) Maximum recommended daily dosage is 2,560 mg (one tablet four times a day) ( 2 ) Metaxalone Tablets 640 mg and SKELAXIN 800 mg tablets are not mutually substitutable on a mg-to-mg basis due to differences in pharmacokinetic profiles ( 5.3 , 12.3 ). When it is appropriate to switch a patient taking SKELAXIN 800 mg on an empty stomach to Metaxalone Tablets, 640 mg ( 2 ): Stop SKELAXIN 800 mg three times a day and start Metaxalone Tablets 640 mg three times a day on an empty stomach OR Stop SKELAXIN 800 mg four times a day and start Metaxalone Tablets 640 mg four times a day on an empty stomach. For patients who have been taking either product with food, do not switch between SKELAXIN 800 mg and Metaxalone Tablets, 640 mg ( 2 ).

3 DOSAGE FORMS AND STRENGTHS Tablets: 800 mg light pink to pink, capsule shaped, scored uncoated tablet with debossing ‘AN’ on the left side of the scoring and ‘553’ on the right side of the scoring. Other side of the tablet is plain. Tablets: 800 mg light pink to pink, capsule shaped, scored uncoated tablet with debossing ‘AN’ on the left side of the scoring and ‘553’ on the right side of the scoring. Other side of the tablet is plain. ( 3 )

4 CONTRAINDICATIONS The use of Metaxalone Tablets, 640 mg is contraindicated in patients with: Known hypersensitivity to any components of this product. Known tendency for drug-induced, hemolytic, or other anemias. Severe renal or hepatic impairment. • Known hypersensitivity to any components of this product. ( 4 ) • Known tendency to drug induced, hemolytic, or other anemias. ( 4 ) • Severe renal or hepatic impairment. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions associated with the use of metaxalone were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most frequent reactions to metaxalone were: CNS : drowsiness, dizziness, headache, and nervousness or “irritability” Digestive : nausea, vomiting, gastrointestinal upset. Other adverse reactions were: Allergic : anaphylaxis have been reported with metaxalone. CNS : cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of metaxalone (within the recommended dosage range) and other serotonergic drugs and with the use of metaxalone as the only serotonergic drug taken at a dosage higher than the recommended dosage [see Warnings and Precautions (5.1) , Drug Interactions (7.2) , and Overdosage (10) ]. Hematologic : leucopenia; hemolytic anemia. Hepatobiliary : jaundice. Immune System : hypersensitivity reaction, rash with or without pruritus. The most common adverse reactions to Metaxalone Tablets, 640 mg include drowsiness, dizziness, headache, and nervousness or “irritability”, nausea, vomiting, gastrointestinal upset. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact INA Pharmaceutics, Inc. at 1-866-835-0469 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS 7.1 Serotonergic Drugs If concomitant use of metaxalone tablets and another serotonergic drug is warranted, carefully observe the patient, particularly during treatment initiation and dosage modification. Discontinue metaxalone tablets if serotonin syndrome is suspected or if it occurs. Serotonin syndrome has resulted from concomitant use of metaxalone tablets (within the recommended dosage range) with other serotonergic drugs [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6 )]. 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). 7.2 CNS Depressants If concomitant use of metaxalone tablets and another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage increases. Due to the additive pharmacologic effect, concomitant use of metaxalone tablets with other CNS depressants may increase the risk of sedation and respiratory depression [see Warnings and Precautions ( 5.2 )]. 7.3 Interaction of Metaxalone Tablets with Benedict’s Tests False-positive Benedict's tests, due to an unknown reducing substance, have been noted in metaxalone tablets-treated patients. A glucose-specific test will differentiate findings.

8 USE IN SPECIFIC POPULATIONS Geriatric Use : Metaxalone tablets-treated geriatric patients may be especially susceptible to CNS depression. ( 8.5 ) 8.1 Pregnancy Risk Summary There are no available data on metaxalone tablets use in pregnant patients to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes despite decades of metaxalone use. Reproduction studies in rats have not revealed effects on the fetus due to metaxalone. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. 8.2 Lactation Risk Summary There are no data available to evaluate the presence of metaxalone or its metabolite in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for metaxalone tablets and any potential adverse effects on the breastfed infant from metaxalone tablets or from the underlying maternal condition. 8.4 Pediatric Use 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 in pediatric patients 13 years of age and older. The safety and effectiveness of metaxalone tablets in pediatric patients 12 years of age or younger have not been established. 8.5 Geriatric Use Clinical studies of metaxalone tablets did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients. Geriatric patients may be especially susceptible to CNS depression associated with metaxalone tablets use [see Warnings and Precautions ( 5.2 )]. The recommended metaxalone tablets dosage in patients 65 years of age and older is the same as in younger adult patients. Metaxalone peak plasma concentrations (C max ) and area under the curve (AUC) were higher in patients 65 years of age and older in the fasted state; however, a clinically significant difference was not observed when metaxalone was administered in the fed state [see Clinical Pharmacology ( 12.3 )]. 8.6 Hepatic Impairment Metaxalone tablets are contraindicated in patients with severe hepatic impairment. Metaxalone tablets should be used with caution and additional follow-up should be considered in patients with mild to moderate hepatic impairment. The effect of hepatic impairment on metaxalone pharmacokinetics is unknown; however, metaxalone undergoes expensive hepatic metabolism [see Clinical Pharmacology ( 12.3 )]. 8.7 Renal Impairment Metaxalone tablets are contraindicated in patients with severe renal impairment. Metaxalone tablets should be used with caution and additional follow-up should be considered in patients with mild to moderate renal impairment. The effect of renal impairment on metaxalone pharmacokinetics is unknown; however, metaxalone undergoes renal excretion as unidentified metabolites [see Clinical Pharmacology ( 12.3 )].

12.1 Mechanism of Action The mechanism of action of metaxalone as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions has not been established, but may be due to general CNS depression. Metaxalone has no direct action on the contractile mechanism of striated muscle, the motor end plate, or the nerve fiber.

DESCRIPTION Metaxalone Tablets, USP are available as 400mg, 400mg tablets are round shaped, light pink tablets. Chemically, metaxalone, USP is 5-[(3,5-dimethylphenoxy)methyl]-2-oxazolidinone. The empirical formula is C 12 H 15 NO 3 , 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 400 mg metaxalone, USP and the following inactive ingredients: alginic acid, corn starch, ferric oxide red, copovidone, magnesium stearate, povidone, pregelatinized starch, sodium alginate. Metaxalone 800 mg - Chemical Structure

10 OVERDOSAGE Clinical Presentation of Metaxalone Overdose Deaths by deliberate or accidental overdose have occurred with metaxalone, particularly in combination with other CNS depressants (including alcohol). CNS manifestations may include CNS depression, agitation, hallucinations, delusions, seizures, respiratory depression, and coma. Cardiovascular effects may include tachycardia and hypertension; hypotension has also been reported. Serotonin syndrome, leading to muscle rigidity, tremor, and hyperthermia, has been reported [see Warnings and Precautions ( 5.1 ), Drug Interactions ( 7.1 , 7.2 )] . Treatment of Metaxalone Overdose The standard of treatment is supportive care. Monitor for CNS and respiratory depression and manage airway with oxygen as needed. Gastrointestinal decontamination procedures (including emesis) should generally be avoided because aspiration may result from CNS depression and seizures. Extracorporeal elimination such as hemodialysis or plasmapheresis have no proven clinical benefit. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

16 HOW SUPPLIED/STORAGE AND HANDLING Metaxalone tablets, USP are available as 800 mg capsule-shaped, scored white to off-white tablet, inscribed with “ 31 90 ” on the scored side and “ WPI ” on the other side. Metaxalone tablets USP, 800 mg has functional scoring. Available as follows. Bottles of 12 NDC 76420-898-12 (repackaged from NDC 0591-2341-01). Bottles of 15 NDC 76420-898-15 (repackaged from NDC 0591-2341-XX). Bottles of 20 NDC 76420-898-20 (repackaged from NDC 0591-2341-XX). Bottles of 30 NDC 76420-898-30 (repackaged from NDC 0591-2341-XX). Bottles of 60 NDC 76420-898-60 (repackaged from NDC 0591-2341-XX). Bottles of 90 NDC 76420-898-90 (repackaged from NDC 0591-2341-XX). Bottles of 100 NDC 76420-898-01 (relabeled from NDC 0591-2341-01). Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].