What is the maximum recommended dose of Exparel (bupivacaine) for local infiltration?

Maximum Exparel Dose for Local Infiltration

The maximum recommended dose of Exparel (liposoam bupivacaine) for local infiltration is 266 mg administered as a single dose, which should not be exceeded in a 24-hour period. 1

FDA-Approved Dosing Parameters

• Exparel is FDA-approved only for infiltration into the surgical site, not for peripheral nerve blocks or neuraxial administration 1, 2
• The 266 mg maximum represents the upper limit established through clinical trials and safety data, with most experience involving single doses up to 225 mg with epinephrine (1:200,000) and 175 mg without epinephrine for standard bupivacaine formulations 1
• This dose should not be repeated within 24 hours to avoid accumulation and potential systemic toxicity 1

Critical Dosing Distinctions from Standard Bupivacaine

• Standard bupivacaine HCl has a maximum dose of 2.5 mg/kg (or up to 3 mg/kg with epinephrine), which translates to approximately 175-225 mg in an average adult 3, 1
• Exparel allows a higher absolute dose (266 mg) because its liposomal formulation provides sustained release, resulting in lower peak plasma concentrations compared to immediate-release bupivacaine 4, 2
• The extended-release mechanism reduces the risk of acute systemic toxicity despite the higher total milligram dose 4

Safety Profile and Monitoring

• Clinical trials involving 335 subjects receiving Exparel doses ranging from 2-310 mg demonstrated a safety profile similar to standard bupivacaine HCl and placebo 2
• The most common adverse events (nausea, pyrexia, pruritus, constipation) were primarily related to opioid rescue medication or the surgical procedure itself rather than the local anesthetic 2
• Nervous system adverse events occurred in 21% of Exparel patients versus 27% with standard bupivacaine, indicating comparable or improved neurologic safety 2

Patient-Specific Dose Adjustments

• Elderly and debilitated patients require dose reduction, though specific percentage reductions are not established in FDA labeling for Exparel 1
• Patients with hepatic or cardiac disease should receive reduced doses, particularly if repeat or continuous administration is anticipated 1, 5
• Weight-based dosing is not explicitly required for Exparel in adults, unlike pediatric bupivacaine dosing where 2.5 mg/kg limits apply 3

Common Pitfalls to Avoid

• Never use Exparel for peripheral nerve blocks despite off-label reports in the literature—it is only FDA-approved for surgical site infiltration 1, 2
• Do not mix Exparel with other local anesthetics in the same syringe, as this may disrupt the liposomal structure and cause immediate release of bupivacaine 1
• Avoid rapid injection of large volumes; use incremental dosing when feasible to detect early signs of intravascular injection 1
• Do not administer more than 266 mg in 24 hours, even if the patient requires additional analgesia—use multimodal alternatives instead 1

Alternative Considerations When Maximum Dose Is Insufficient

• If 266 mg Exparel provides inadequate coverage for a large surgical field, consider supplementing with shorter-acting local anesthetics (lidocaine) in separate anatomic planes rather than exceeding the Exparel maximum 1
• Multimodal analgesia with acetaminophen, NSAIDs, and regional techniques should be employed rather than pushing local anesthetic doses to toxic thresholds 3, 6

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