Metaxalone

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 )

Tablets: 640 mg oval, peach-colored, debossed with M640 on one side and without markings on the other side. Tablets: 640 mg. ( 3 )

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 )

Serotonin Syndrome : 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. If concomitant use with another serotonergic drug is warranted, carefully observe the patient, particularly during treatment initiation and dosage increases. Discontinue Metaxalone Tablets, 640 mg if serotonin syndrome is suspected or it occurs. ( 5.1 , 7.1 ) Central Nervous System (CNS) Depression : Metaxalone Tablets, 640 mg may impair mental and/or physical abilities required for the performance of hazardous tasks, such as operating machinery or driving a motor vehicle, and may enhance the effects of other CNS depressants including alcohol. Follow patients closely for signs and symptoms of respiratory depression and sedation. If concomitant use with another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage increases. ( 5.2 , 7.2 ) Risk with Inappropriate Switching to Metaxalone Tablets, 640 mg Inappropriate switching on a mg-to-mg basis from SKELAXIN (metaxalone) tablets, 800 mg to Metaxalone Tablets, 640 mg to achieve the same total daily metaxalone dosage may result in a clinically significant increase in metaxalone exposure which may increase the risk of metaxalone-associated adverse reactions including CNS depression. Metaxalone Tablets, 640 mg and SKELAXIN (metaxalone) tablets, 800 mg are not mutually substitutable on a mg-to-mg basis ( 5.3 , 12.3 ).

5.1 Serotonin Syndrome 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 [see Drug Interactions (7) ] and with the use of metaxalone as the only serotonergic drug taken at a dosage higher than the recommended dosage [see Overdosage (10) ] . 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 Drug Interactions (7.2) ] . 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 after initiation of a serotonergic drug but may occur later than that. If concomitant use of Metaxalone Tablets, 640 mg and another serotonergic drug is warranted, reassess the patient, particularly during treatment initiation and dosage modification. Discontinue Metaxalone Tablets, 640 mg if serotonin syndrome is suspected or occurs.

5.2 Central Nervous System Depression Because of central nervous system (CNS) depressant effects, 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 other CNS depressants including alcohol. Geriatric patients may be especially susceptible to CNS depression associated with metaxalone use. When used concomitantly, the sedative effects of metaxalone and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive [see Drug Interactions (7) ]. Follow patients treated with Metaxalone Tablets, 640 mg closely for signs and symptoms of respiratory depression and sedation. If concomitant use of metaxalone and another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage increases.

5.3 Risk with Inappropriate Switching to Metaxalone Tablets, 640 mg Inappropriate switching on a mg-to-mg basis from SKELAXIN (metaxalone) tablets, 800 mg to Metaxalone Tablets, 640 mg to achieve the same total daily metaxalone dosage may result in a clinically significant increase in metaxalone exposure which may increase the risk of metaxalone-associated adverse reactions including CNS depression. For example, it is inappropriate to switch from four SKELAXIN 800 mg tablets (3,200 mg) per day to five tablets of Metaxalone Tablets, 640 mg (3,200 mg) per day [1.25 times the maximum recommended daily dosage of 2,560 mg] [see Dosage and Administration (2) ]. Metaxalone Tablets 640 mg and SKELAXIN (metaxalone) tablets, 800 mg are not mutually substitutable on a mg-to-mg basis [see Clinical Pharmacology (12.3) ] . It is generally inappropriate to switch between Metaxalone Tablets, 640 mg and SKELAXIN 800 mg to mediate metaxalone-associated adverse reactions. For recommendations on how to switch from SKELAXIN (metaxalone) tablets, 800 mg, to Metaxalone Tablets, 640 mg, see Dosage and Administration (2) .

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.

7.1 Serotonergic Drugs If concomitant use of Metaxalone Tablets, 640 mg and another serotonergic drug is warranted, carefully observe the patient, particularly during treatment initiation and dosage modification. Discontinue Metaxalone Tablets, 640 mg if serotonin syndrome is suspected or if it occurs. Serotonin syndrome has resulted from concomitant use of metaxalone (within the recommended dosage range) and other serotonergic drugs [see Warnings and Precautions (5.1) ]. 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).

7.2 Depressants If concomitant use of Metaxalone Tablets, 640 mg and another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage modification. Due to the additive pharmacologic effect, concomitant use of Metaxalone Tablets, 640 mg with other CNS depressants may increase the risk of sedation and respiratory depression [see Warnings and Precautions (5.2) ].

7.3 Interaction of Metaxalone with Benedict’s Tests False-positive Benedict's tests, due to an unknown reducing substance, have been noted in metaxalone-treated patients. A glucose-specific test will differentiate findings.

Geriatric Use : Geriatric patients may be especially susceptible to CNS depression associated with Metaxalone Tablets, 640 mg use. ( 8.5 ) Hepatic Impairment : Consider additional monitoring in patients with mild to moderate hepatic impairment. ( 4 , 8.6 ) Renal impairment : Consider additional monitoring in patients with mild to moderate renal impairment ( 4 , 8.7 )

8.1 Pregnancy Risk Summary There are no available data on metaxalone use in pregnancy 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 evidence of impaired fertility or harm to 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 on 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 and any potential adverse effects on the breastfed infant from metaxalone or from the underlying maternal condition.

8.4 Pediatric Use 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 pediatric patients 13 years of age and older. The safety and effectiveness of Metaxalone Tablets, 640 mg in pediatric patients less than 13 years of age have not been established.

8.5 Geriatric Use Clinical studies of Metaxalone Tablets, 640 mg did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients. The effects of age on the pharmacokinetics of Metaxalone Tablets, 640 mg have not been evaluated. Geriatric patients may be especially susceptible to CNS depression associated with metaxalone use [see Warnings and Precautions (5.2) ].

8.6 Hepatic Impairment Metaxalone Tablets. 640 mg are contraindicated in patients with severe hepatic impairment . Metaxalone Tablets, 640 mg should be used with caution and additional monitoring should be considered in patients with mild to moderate hepatic impairment. The effect of hepatic impairment on metaxalone pharmacokinetics is unknown; however, metaxalone undergoes extensive hepatic metabolism [see Clinical Pharmacology (12.3) ] .

8.7 Renal Impairment Metaxalone Tablets, 640 mg are contraindicated in patients with severe renal impairment . Metaxalone Tablets, 640 mg should be used with caution and additional monitoring 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) ] .

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.