Metaxalone

Metaxalone is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults and pediatric patients 13 years of age and older. Metaxalone 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 adults and pediatric patients 13 years of age and older. ()

The recommended dosage of metaxalone in adults and pediatric patients 13 years of age and older is 800 mg orally three to four times a day . Metaxalone Tablets 800 mg are not substitutable on a mg to mg basis with Metaxalone Tablets, 640 mg . When it is appropriate to switch: • Switch only in patients who have been taking Metaxalone Tablets, 640 mg on an empty stomach. • Stop Metaxalone Tablets, 640 mg three times a day and start Metaxalone Tablets 800 mg three times a day on an empty stomach, OR stop Metaxalone Tablets 640 mg four times a day and start Metaxalone Tablets 800 mg four times a day on an empty stomach. Do not switch from Metaxalone Tablets, 640 mg to Metaxalone Tablets, 800 mg when the patient is taking food during administration. • Recommended dosage of metaxalone in adults and pediatric patients 13 years of age and older is 800 mg orally three to four times a day. • Metaxalone Tablets 800 mg are not substitutable on a mg to mg basis with Metaxalone Tablets, 640 mg. When it is appropriate to switch, see the Full Prescribing Information on switching instructions.

5 WARNINGS AND PRECAUTIONS • 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 is warranted, carefully observe the patient, particularly during treatment initiation and dosage increases. Discontinue metaxalone if serotonin syndrome is suspected or it occurs. ( 5.1 , 7.1 ) • Central Nervous System (CNS) Depression : Metaxalone may impair mental and/or physical abilities required for the performance of hazardous tasks, such as operating machinery or driving a motor vehicle, especially when used with other CNS depressants including alcohol. Follow patients closely for signs and symptoms of respiratory depression and sedation. If concomitant use is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage increases. ( 5.2 , 7.2 )

5.1Serotonin 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 . 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 and another serotoneric drug is warranted, reassess the patient, particularly during treatment initiation and dosage increases.

Discontinue metaxalone if serotonin syndrome is suspected or it occurs.

5.2Central Nervous System Depression Because

of its 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 . Follow metaxalone-treated patients 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.

Metaxalone is contraindicated in patients with: • Known hypersensitivity to any component of metaxalone. • Known tendency to drug induced, hemolytic, or other anemias. • Severe renal or hepatic impairment. • Known hypersensitivity to any components of this product. • Known tendency to drug induced, hemolytic, or other anemias. • Severe renal or hepatic impairment.

8.1Pregnancy Risk Summary There

are no available data on metaxalone 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.

8.4Pediatric Use Metaxalone

is 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 in pediatric patients 12 years of age or younger have not been established.

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: • CNS: cases of serotonin syndrome 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 at a dosage higher than the recommended dosage . • Hematologic: leukopenia; hemolytic anemia; • Hepatobiliary: jaundice; • Immune System: anaphylaxis, hypersensitivity reaction, rash with or without pruritus. Most common adverse reactions (incidence >5%) are nausea and vomiting. () To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .