Postmortem Metaxalone (Skelaxin®) Data from North Carolina.

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 ≤4 mg/L. The selected case studies offer valuable information regarding postmortem interpretation.

A rare fatality attributed solely to metaxalone.

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.

Serotonin syndrome associated with metaxalone overdose.

INTRODUCTION: Serotonin syndrome is a potentially life-threatening entity associated with pro-serotonergic medications in therapeutic use, in overdose, or when co-administered with other drugs. A broad range of drugs and drug combinations have been associated with serotonin syndrome. Metaxalone overdose associated with serotonin syndrome has not been previously reported. CASE REPORT: (Case 1) A 23-year-old female overdosed on tramadol and metaxalone. She developed dysautonomia, diaphoresis, lower extremity rigidity and spontaneous clonus, flaccid upper extremities, and hyperthermia 5 h after ingestion. Her course was complicated by status epilepticus. (Case 2) A 56-year-old female overdosed on metaxalone and was found unresponsive. She developed dysautonomia, lower extremity rigidity and spontaneous clonus, flaccid upper extremities, rhabdomyolysis, acute renal failure, and hyperthermia. Non-depolarizing neuromuscular blockade and cooling blankets were required to control hyperthermia in both cases. Serum metaxalone levels were markedly elevated in both cases. CONCLUSION: These are the first reported cases of metaxalone overdose associated with serotonin syndrome, which may be related to monoamine oxidase inhibition.

Pediatric metaxalone ingestions reported to Texas poison control centers, 2000-2007.

OBJECTIVES: The purpose of this study was to describe the pattern of metaxalone ingestions by young children reported to poison control centers. METHODS: Cases were all metaxalone ingestions by patients aged 0 to 5 years reported to Texas poison control centers during 2000 to 2007. Cases with multiple substance ingestions and lack of follow-up were excluded. Cases were analyzed for selected demographic and clinical factors. RESULTS: Of 148 total cases, 56.8% were boys. The distributions by management site were 56.1% on-site, 22.3% already at/en route to a health care facility, and 21.6% referred to a health care facility. Final medical outcomes were no effect for 90.5% cases, minor effect for 8.1%, moderate effect for 0.7%, and major effect for 0.7%. Specific clinical effects reported were drowsiness (11), vomiting (3), agitation (2), rash (1%), tachycardia (1), and ataxia (1). CONCLUSIONS: Pediatric metaxalone ingestions reported to Texas poison control centers usually resulted in minor or no effect. Most ingestions did not require hospitalization.

Adult metaxalone ingestions reported to Texas poison control centers, 2000-2006.

Few data exist on potentially adverse metaxalone (Skelaxin(R)) ingestions in adults. All metaxalone ingestions involving patients aged >or=20 years during 2000-2006 were retrieved from Texas poison control centers. Exclusion criteria were lack of follow-up or multiple substance ingestion. Cases were analyzed for selected demographic and clinical factors. Of the 142 patients, 66.2% were female. Dose ingested was reported for 61 patients. Of those cases with a reported dose, distribution by management site was 29.5% on-site, 59.0% already at/en route to health care facility, and 11.5% referred to health care facility. Final medical outcome was 'no effect' for 50.8% cases, 'minor effect' for 31.1%, and 'moderate effect' for 18.0%. The more common adverse clinical effects reported were drowsiness (27.9%), tachycardia (6.6%), agitation (6.6%), nausea (4.9%), dizziness (4.9%), slurred speech (4.9%), and tremor (4.9%). A moderate medical outcome occurred in 13.6% of ingestions of 2400 mg. Management involved a health care facility in 18.2% of ingestions of 2400 mg. This study found that adult ingestions of higher doses of metaxalone, particularly >2400 mg, were associated with more serious medical outcomes and were managed at health care facilities. This study also proposes triage guidelines for when ingestions can be safely managed at home.

A fatality involving metaxalone.

A case is presented of a 54-year-old white female found dead in a secured apartment. Postmortem toxicologic analysis of the heart blood identified acetaminophen (97 mg/L), citalopram (0.4 mg/L), gabapentin (24 mg/L) and metaxalone (21 mg/L). The metaxalone concentration is within the range of previously reported fatalities involving metaxalone. The medical examiner ruled that the cause of death was metaxalone and gabapentin intoxication and the manner of death was suicide.

Metaxalone (Skelaxin)-related death.

The case history and toxicological findings of a fatal multi-drug overdose involving metaxalone (Skelaxin) are presented. Gas-liquid chromatography with flame-ionization detection and gas chromatography-mass spectrometry were used to determine the following drug concentrations (mg/L) in aortic blood: 19 mg/L metaxalone; 190 mg/L acetaminophen; 0.28 mg/L hydrocodone; and < 0.1 mg/L diazepam, nordiazepam, amitriptyline, and nortriptyline. The following concentrations of metaxalone were reported in alternate specimens: 17 mg/L in femoral blood; 44 mg/L in bile; 70 mg/kg in liver; 7 mg/L in urine; 202 mg/kg in gastric contents; and 14 mg/L in vitreous humor. These concentrations were determined using both direct extraction and the method of standard addition. The quantitative results obtained by both procedures were in good agreement. Because of the limited information published on metaxalone toxicity, the pathologist assigned the manner and cause of death as accidental acute hydrocodone intoxication. Four additional cases in which metaxalone was present were analyzed for comparison. Two cases were probable drug-related deaths and had metaxalone aorta blood concentrations of 18 and 11 mg/L. The other two cases had therapeutic metaxalone concentrations in the aortic blood of < 0.75 and 2.1 mg/L.

Polydrug fatality involving metaxalone.

A 29-year old female with a history of depression was found dead in a hotel room. The death scene investigation found empty pill bottles and an empty liter bottle of wine. Metaxalone, a centrally acting muscle relaxant, along with citalopram, ethanol, and chlorpheniramine were identified in the postmortem samples and quantitated by gas chromatography-mass spectrometry. The concentration of metaxalone in femoral vein blood was 39 mg/L. The heart blood concentration was 54 mg/L. Femoral vein blood concentrations of citalopram and chlorpheniramine were 0.77 mg/L and 0.04 mg/L, respectively. Ethanol levels were 0.13 g/dL in vitreous and 0.08 g/dL in heart blood. Other tissue samples were also analyzed. The authors consider the metaxalone concentrations toxic and potentially fatal. The citalopram concentrations were lower than those reported in fatal cases for this drug alone. Death was ascribed to polydrug abuse/overdose with metaxalone a major contributor. This represents the first reported case to our knowledge in which a metaxalone overdose significantly contributed to death.