What are the side effects of Metaxalone (muscle relaxant)?

Metaxalone Side Effects

Metaxalone causes primarily central nervous system adverse effects including drowsiness, dizziness, headache, and irritability, along with gastrointestinal symptoms such as nausea and vomiting, and carries serious contraindications in patients with significant hepatic or renal dysfunction due to risks of drug-induced anemia and hematologic complications. 1

Common Central Nervous System Effects

The most frequently reported adverse reactions to metaxalone involve CNS depression 1:

• Drowsiness is the most common side effect, occurring in approximately 28% of adult ingestions 2
• Dizziness affects roughly 5% of patients 2
• Headache is a frequent complaint 1
• Nervousness or irritability can occur 1
• Slurred speech has been reported in approximately 5% of cases 2

These CNS effects are dose-dependent and become more pronounced at higher doses, particularly above 2400 mg 2.

Gastrointestinal Side Effects

Digestive system complaints are common 1:

• Nausea occurs in approximately 5% of patients 2
• Vomiting is reported in some cases 1, 2
• General gastrointestinal upset 1

Serious Hematologic and Hepatic Risks

Metaxalone is contraindicated in patients with significant hepatic or renal dysfunction 3, 4:

• Hemolytic anemia has been reported 1
• Leukopenia (low white blood cell count) 1
• Drug-induced anemia 3
• Jaundice indicating hepatobiliary toxicity 1

Cardiovascular Effects

• Tachycardia (rapid heart rate) occurs in approximately 7% of cases 2
• In overdose scenarios, heart rates as high as 208 beats per minute have been documented 5

Hypersensitivity and Allergic Reactions

• Rash with or without pruritus (itching) 1
• Anaphylactoid reactions, though rare, have been reported 1

Neuromuscular Effects

• Tremor affects approximately 5% of patients 2
• Agitation occurs in about 7% of cases 2
• Ataxia (loss of coordination) has been reported 6

Serious Toxicity in Overdose

At supratherapeutic concentrations (above 31 mcg/mL, compared to therapeutic peak of 0.9 mcg/mL), metaxalone can cause severe complications 5:

• Serotonin syndrome when combined with selective serotonin reuptake inhibitors, characterized by altered mental status, hyperthermia (temperatures up to 41.6°C), rigidity, myoclonus, and hyperreflexia 5
• Seizure-like activity 5
• Severe hyperthermia requiring active cooling 5

This occurs because metaxalone demonstrates significant monoamine oxidase A (MAO-A) inhibition at toxic concentrations (140-276 µM), creating dangerous interactions with serotonergic medications 7.

Dose-Related Outcomes

Ingestions exceeding 2400 mg are associated with more serious medical outcomes 2:

• Moderate medical outcomes occurred in 13.6% of ingestions ≤2400 mg versus 20.5% of ingestions >2400 mg 2
• All ingestions >2400 mg required management at healthcare facilities 2

Critical Clinical Considerations

Metaxalone should be held on the day of surgical procedures due to potential for increased sedation when combined with anesthetic agents and other CNS depressants 3, 4. The combination of metaxalone with opiates or other CNS depressants significantly increases sedation risk 3.

Comparative Safety Profile

Among commonly prescribed skeletal muscle relaxants, metaxalone has the fewest reports of side effects and no reports of major safety issues related to dependence or abuse potential, unlike carisoprodol which carries significant risk of physical and psychological dependence 8. However, the serious contraindications in hepatic and renal disease must be respected 3, 4.