Metaxalone

Metaxalone(AHR438;NSC170959) is a muscle relaxant used to relax muscles. Target: Others Metaxalone is a muscle relaxant used to relax muscles and relieve pain caused by strains, sprains, and other musculoskeletal conditions. Its exact mechanism of action is not known, but it may be due to general central nervous system depression. It is considered to be a moderately strong muscle relaxant, with relatively low incidence of side effects.

References:
[1]. http://en.wikipedia.org/wiki/Metaxalone

Serotonin syndrome following metaxalone overdose and therapeutic use of a selective serotonin reuptake inhibitor.[Pubmed:25671244]

Clin Toxicol (Phila). 2015 Mar;53(3):185-7.

UNLABELLED: Metaxalone has only recently been associated with serotonin syndrome. The mechanism of action of this centrally acting muscle relaxant is unknown; however, the observation of serotonin syndrome in patients with Metaxalone overdose suggests a role in the serotonergic pathway. CASE REPORT: (Case 1) A 29-year-old woman with overdose of Metaxalone presented to the emergency department with altered mental status, seizure-like activity, hyperthermia, rigidity in the lower extremities, myoclonus, and hyperreflexia. Vital signs on arrival include blood pressure of 168/80 mmHg, heart rate of 208 beats per minute (bpm), respirations of 20/min, a temperature of 41.6 degrees C rectally, and room air oxygen saturation of 97%. She was intubated and sedated with benzodiazepines, and actively cooled. Serum paroxetine concentration was 23 (therapeutic range: 20-200) ng/mL, and serum Metaxalone concentration was 31 mcg/mL (peak plasma concentrations average 0.9 mcg/mL at 3.3 h following a single oral dose of 400 mg). (Case 2) A 27-year-old man presented to the emergency department with altered mental status, rigidity in his lower extremities, myoclonus, and hyperreflexia. Vital signs on arrival include blood pressure of 158/131 mmHg, heart rate of 126 bpm, respiratory rate of 20 breaths per minute, and temperature of 37.2 degrees C, with oxygen saturation of 98% on room air. His medication list included Metaxalone and escitalopram. He was managed aggressively with IV boluses of diazepam, in total 80 mg, in the emergency department. Serum escitalopram concentration was 24 ng/mL with a therapeutic range of 21-64 ng/mL, and serum Metaxalone concentration was 58 mcg/mL. CONCLUSION: These two cases suggest that at supratherapeutic concentrations Metaxalone has serotonergic effects. Severe serotonin toxicity may result from Metaxalone abuse in individuals using a selective serotonin reuptake inhibitor therapeutically.

A rare fatality attributed solely to metaxalone.[Pubmed:25673649]

J Anal Toxicol. 2015 May;39(4):321-3.

Metaxalone (Skelaxin) is a prescription medication used primarily as a centrally acting skeletal muscle relaxer and is rarely implicated in drug fatalities. We present a case study involving a relatively young decedent where Metaxalone is implicated as the sole agent causing death with little in the way of confounding factors. The concentration of Metaxalone in hospital admission blood was determined to be 37.4 mcg/mL. In postmortem specimens the concentrations were shown to be 13.5 mcg/mL (heart blood), 4.9 mcg/mL (vitreous humor), 69.4 mcg/g (liver) and 74.0 mcg/g (brain). Additionally a blood-to-plasma (b/p) ratio was estimated using antemortem blood and serum specimens taken at the same time on the second day following admission. The b/p ratio was calculated to be 1.4 implying a higher proportion of the drug to be found in whole blood versus plasma/serum samples, an important factor which should be taken into account when comparing blood concentrations to published therapeutic ranges determined in serum/plasma.

Postmortem Metaxalone (Skelaxin(R)) Data from North Carolina.[Pubmed:26378137]

J Anal Toxicol. 2015 Oct;39(8):629-36.

The North Carolina Office of the Chief Medical Examiner Toxicology Laboratory identified 61 cases from 2002 to 2014 where Metaxalone was detected during routine postmortem drug screening in support of a determination of cause and manner of death. Decedents were divided into groups based on the manner of death with the goal of studying Metaxalone concentrations in overdose and non-overdose situations (natural, accident, suicide and undetermined). Subgroups were established for cases in which Metaxalone contributed to the cause of death (attributed) and cases in which it did not (unattributed). Attributed cases were divided into those where Metaxalone additively combined with other drugs and cases in which the drug was present in sufficient amounts to be the primary cause of death, regardless of other drugs present and the concentrations of those drugs. The mean Metaxalone concentration for the additive deaths was 14.2 mg/L with a median value of 11 mg/L (n = 18) and a mean Metaxalone concentration of 36.7 mg/L with a median value of 32 mg/L (n = 9) for primary deaths. For unattributed Metaxalone concentrations, the mean was 3.4 mg/L with a median value of 2.9 mg/L (n = 31). Of the 61 cases, 34% fall at or below a therapeutic concentration of