Usage
Metaxalone is a centrally-acting skeletal muscle relaxant indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions. It is not a peripherally-acting muscle relaxant and does not directly relax muscles. Its exact mechanism is not fully understood, but it is believed to work by depressing the central nervous system (CNS).
Alternate Names
Metaxalone is also known by the brand name Skelaxin®. There are generic formulations available as well.
How It Works
Pharmacodynamics: Metaxalone’s precise mechanism of action is unknown, but it is believed to primarily act at the spinal cord level, inhibiting polysynaptic reflexes involved in muscle spasm and pain. It may also possess some sedative properties. It does not directly relax tense skeletal muscles.
Pharmacokinetics:
- Absorption: Metaxalone is readily absorbed from the gastrointestinal tract. The 800 mg formulation reaches peak plasma concentration in about 3 hours. Food may delay absorption.
- Metabolism: Metaxalone is extensively metabolized in the liver, primarily via CYP3A4 and, to a lesser extent, CYP1A2 and CYP2E1. A major metabolite may also contribute to the pharmacologic effects.
- Elimination: The drug and its metabolites are primarily excreted in the urine. The elimination half-life is approximately 2-3 hours.
Mode of Action (Cellular/Molecular Level): While the exact mechanism remains unclear, current research suggests that Metaxalone’s effects may involve:
- Inhibition of polysynaptic reflexes in the spinal cord: Reducing the transmission of nerve impulses involved in muscle contraction and spasm.
- Modulation of neurotransmitter systems: This may include effects on gamma-aminobutyric acid (GABA), serotonin, and dopamine systems within the CNS.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: The exact receptor interactions and neurotransmitter modulation of metaxalone are not fully elucidated. However, it is suspected to affect GABAergic and serotonergic pathways.
Dosage
Standard Dosage
Adults:
The recommended dosage for adults and pediatric patients 13 years and older is 800 mg orally three to four times a day. The maximum recommended daily dose is 3200 mg.
Children:
The safety and efficacy of metaxalone have not been established in pediatric patients younger than 13 years.
Special Cases:
- Elderly Patients: Use with caution due to increased risk of CNS adverse effects and age-related decline in hepatic and renal function. Dosage adjustments may be necessary.
- Patients with Renal Impairment: Metaxalone is contraindicated in patients with severe renal impairment. Use with caution and monitor closely in patients with mild to moderate renal impairment. Dosage adjustments may be necessary.
- Patients with Hepatic Dysfunction: Metaxalone is contraindicated in patients with severe hepatic impairment. Use with caution and monitor closely in patients with mild to moderate hepatic impairment. Dosage adjustments may be necessary.
- Patients with Comorbid Conditions: Use with caution in patients with pre-existing conditions such as cardiovascular disease, respiratory disease, or depression, as these conditions may increase the risk of adverse effects.
Clinical Use Cases
Metaxalone is not typically indicated for use in the following clinical settings: intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations such as status epilepticus or cardiac arrest. Other muscle relaxants and sedatives are typically preferred in these contexts.
Dosage Adjustments
Dosage adjustments are recommended for patients with renal or hepatic impairment. Start at the lower end of the dosing range and titrate cautiously based on patient response and tolerability. For elderly patients, initiate therapy with a lower dose and monitor closely.
Side Effects
Common Side Effects
Drowsiness, dizziness, headache, nausea, vomiting, upset stomach, irritability, and nervousness.
Rare but Serious Side Effects
Leukopenia, hemolytic anemia, allergic reactions (e.g., skin rash, itching, angioedema), serotonin syndrome, hepatotoxicity.
Long-Term Effects
Long-term effects are not well studied, but chronic use may be associated with dependence and withdrawal symptoms upon discontinuation.
Adverse Drug Reactions (ADR)
Serotonin syndrome (with higher doses or concurrent use with serotonergic drugs), severe allergic reactions, hepatotoxicity.
Contraindications
Hypersensitivity to metaxalone, significant hepatic impairment, significant renal impairment, known tendency to drug-induced hemolytic or other anemias.
Drug Interactions
CNS depressants (e.g., alcohol, opioids, benzodiazepines, barbiturates): Increased risk of CNS depression (sedation, respiratory depression).
Serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs, triptans): Increased risk of serotonin syndrome.
CYP3A4 inhibitors (e.g., some antifungals, some antibiotics, grapefruit juice): Increased metaxalone levels and potential for adverse reactions.
CYP3A4 inducers (e.g., rifampin, carbamazepine): Decreased metaxalone levels and potential for reduced efficacy.
Pregnancy and Breastfeeding
Pregnancy Safety Category: Not established. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Breastfeeding: It is unknown if metaxalone is excreted in human breast milk. Use caution while breastfeeding.
Drug Profile Summary
- Mechanism of Action: CNS depressant, inhibiting polysynaptic reflexes in the spinal cord.
- Side Effects: Drowsiness, dizziness, headache, nausea, vomiting, serotonin syndrome (rare).
- Contraindications: Hypersensitivity, severe hepatic/renal impairment, drug-induced anemias.
- Drug Interactions: CNS depressants, serotonergic drugs, CYP3A4 inhibitors/inducers.
- Pregnancy & Breastfeeding: Use with caution. Safety not fully established.
- Dosage: Adults and children ≥13 years: 800 mg TID or QID. Max 3200 mg/day.
- Monitoring Parameters: Liver function tests (LFTs), complete blood count (CBC), signs and symptoms of CNS depression and serotonin syndrome.
Popular Combinations
Metaxalone is often combined with analgesics such as NSAIDs or acetaminophen for enhanced pain relief. However, caution is needed when combining metaxalone with opioids due to increased risk of respiratory depression.
Precautions
- General Precautions: Evaluate patients for renal and hepatic function, and pre-existing anemias.
- Specific Populations: Use with caution in elderly, pregnant/breastfeeding, and those with renal/hepatic impairment. Not established for use in children under 13 years old.
- Lifestyle Considerations: Avoid alcohol and activities requiring alertness.
FAQs
A: For adults and pediatric patients 13 years and older, the recommended dosage is 800 mg orally three to four times daily, not to exceed 3200 mg daily. The safety and efficacy in children under 13 have not been established.
A: Its precise mechanism is not fully understood, but it is believed to depress the CNS, inhibiting polysynaptic reflexes in the spinal cord to reduce muscle spasm.
A: Common side effects include drowsiness, dizziness, headache, nausea, vomiting, and gastrointestinal upset.
A: Serious, though rare, side effects include leukopenia, hemolytic anemia, allergic reactions, serotonin syndrome, and hepatotoxicity.
A: Metaxalone is contraindicated in patients with hypersensitivity to the drug, significant hepatic or renal impairment, and a known tendency to drug-induced hemolytic or other anemias.
A: Important drug interactions include those with CNS depressants (increased CNS depression), serotonergic drugs (increased risk of serotonin syndrome), and CYP3A4 inhibitors/inducers (altered metaxalone levels).
A: Metaxalone’s safety during pregnancy and breastfeeding has not been fully established. Use with caution and only if the potential benefit outweighs the potential risk.
A: Patients should avoid alcohol and activities requiring mental alertness, such as driving or operating machinery, while taking metaxalone due to the risk of drowsiness and impaired cognitive function.
Q9: Should dosage adjustments be considered for elderly patients?
A: Yes, elderly patients are more susceptible to adverse effects, particularly CNS effects, and may require lower doses and closer monitoring.
A: Metaxalone tablets should be taken orally three or four times a day with or without food, however, 800mg tablets (Skelaxin®) should be taken without food. The 640 mg and 800 mg metaxalone tablets are not interchangeable on a mg to mg basis. If a dose is missed, it can be taken as soon as possible. Never double up on doses.
