metaxalone

Metaxalone tablets are 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 [see Use in Specific Populations ]. Metaxalone tablets 800 mg are not substitutable on a mg to mg basis with metaxalone tablets, 640 mg [see Clinical Pharmacology ]. 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 tablets 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.

12.1 Mechanism of Action Metaxalone’s mechanism of action has not been fully characterized, but may be related to its sedative properties. Metaxalone has no direct action on the contractile mechanism of striated muscle, the motor end plate, or the nerve fiber.

The following adverse reactions associated with the use of metaxalone were identified in clinical studies or post-marketing 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 [see Warnings and Precautions , Drug Interactions and Overdosage ] . 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 AvKARE at 1-855-361-3993;email [email protected] or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7.1 Serotonergic Drugs If concomitant use of metaxalone and another serotoneric drug is warranted, carefully observe the patient, particularly during treatment initiation and dosage modification. Discontinue metaxalone if serotonin syndrome is suspected or if it occurs. Serotonin syndrome has resulted from concomitant use of metaxalone (within the recommended dosage range) with other serotonergic drugs [see Warnings and Precautions and Adverse Reactions ]. 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 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 with other CNS depressants may increase the risk of sedation and respiratory depression [see Warnings and Precautions ]. 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 : Metaxalone-treated geriatric patients may be especially susceptible to CNS depression. 8.1 Pregnancy 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. 8.2 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 and any potential adverse effects on the breastfed infant from metaxalone or from the underlying maternal condition. 8.4 Pediatric 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. 8.5 Geriatric Use Clinical studies of metaxalone 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 use [see Warnings and Precautions ]. The recommended metaxalone 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 ]. 8.6 Hepatic Impairment Metaxalone is contraindicated in patients with severe hepatic impairment. Metaxalone 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 ] . 8.7 Renal Impairment Metaxalone is contraindicated in patients with severe renal impairment. Metaxalone 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 ].