• Skelaxin may enhance the effects of alcohol and other CNS depressants.

• Metaxalone should be administered with great care to patients with pre-existing liver damage. Serial liver function studies should be performed in these patients.
• Taking  Skelaxin with food may enhance general CNS depression; elderly patients may be especially susceptible to this CNS effect.
• The carcinogenic potential of metaxalone has not been determined.
• Metaxalone tablets should not be used in women who are or may become pregnant and particularly during early pregnancy unless, in the judgement of the physician, the potential benefits outweigh the possible hazards.
• It is not known whether this drug is secreted in human milk. As a general rule, nursing should not be undertaken while a patient is on a drug since many drugs are excreted in human milk.
• Safety and effectiveness in children of 12 years  and below have not been established. 

The most frequent reactions to metaxalone include:

CNS: drowsiness, dizziness, headache, and nervousness or "irritability";

Digestive: nausea, vomiting, gastrointestinal upset.

Other adverse reactions are:

Immune System: hypersensitivity reaction, rash with or without pruritus;

Hematologic: leukopenia; hemolytic anemia;

Hepatobiliary: jaundice.

Though rare, anaphylactoid reactions have been reported with metaxalone.