What is the pharmacology of Exparel (bupivacaine)?

From the Guidelines

Exparel, a liposomal formulation of bupivacaine, is a local anesthetic that provides prolonged pain relief over 72-96 hours after a single administration, with a typical dose ranging from 133 mg to 266 mg depending on the surgical site and desired duration of effect. The pharmacology of Exparel is based on its unique liposomal delivery system, which allows for extended release of bupivacaine, a local anesthetic that works by blocking sodium channels in nerve membranes, preventing the initiation and conduction of nerve impulses 1.

Key Characteristics of Exparel

• Extended release of bupivacaine over 72-96 hours
• Typical dose: 133 mg to 266 mg
• Administration: local infiltration into the surgical site or as a nerve block
• Contraindications: intravenous or intra-articular administration

Important Considerations

• Wait at least 20 minutes before administering other local anesthetics to avoid rapid release of bupivacaine from the liposomal particles
• Common side effects: nausea, constipation, and vomiting
• Caution in patients with cardiovascular disease, liver impairment, or those taking medications that might interact with bupivacaine
• The extended-release nature of Exparel reduces the need for opioid medications post-surgery, potentially decreasing opioid-related side effects and the risk of dependence.

Maximum Recommended Doses

According to the guidelines, the maximum recommended dose of bupivacaine with epinephrine is 3.0 mg/kg, and without epinephrine is 1.3 mg/kg 1. It's essential to calculate the maximum allowable safe dosage before administration to avoid excessive dosing.

Comparison with Other Local Anesthetics

Exparel's unique liposomal delivery system distinguishes it from other local anesthetics, such as lidocaine and mepivacaine, which have shorter durations of action and may require multiple administrations to achieve similar pain relief 1.

From the FDA Drug Label

Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino, or piperidine group. Bupivacaine Hydrochloride is 2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-, monohydrochloride, monohydrate, a white crystalline powder that is freely soluble in 95 percent ethanol, soluble in water, and slightly soluble in chloroform or acetone.

The pharmacology of Exparel (bupivacaine) involves its classification as a local anesthetic that is chemically related to other aminoacyl local anesthetics like mepivacaine and lidocaine. Bupivacaine works by blocking the generation and conduction of nerve impulses, thereby producing local anesthesia. Its chemical structure consists of an amide linkage between the aromatic nucleus and the amino or piperidine group.

• Key characteristics of bupivacaine include its solubility in water and ethanol, and its slight solubility in chloroform or acetone.
• Pharmacological properties are related to its ability to produce vasodilation by blocking sympathetic nerves, which can lead to maternal hypotension in obstetrical use.
• Clinical use of bupivacaine includes local infiltration, peripheral nerve block, and epidural blocks, with considerations for dosage and administration in different patient populations, such as pediatric and geriatric patients 2, 2.

From the Research

Pharmacology of Exparel (Bupivacaine)

• Exparel, a long-lasting liposomal bupivacaine local anesthetic agent, has significant benefits in the management of postoperative pain 3.
• It is currently the only extended-release formulation of bupivacaine approved by the FDA for infiltration of the tissues during surgery and for interscalene nerve block analgesia following shoulder surgery 4.
• The use of Exparel may be a significant component for postoperative multimodal pain control owing to its efficacy and long duration of action 3.

Mechanism of Action

• Exparel encapsulates bupivacaine in biodegradable liposomes, allowing for sustained release and longer duration of action 4.
• The novel polymer technology in bupivacaine/meloxicam PR allows simultaneous diffusion of bupivacaine and meloxicam over 72 hours 5.

Efficacy and Safety

• Available data suggest relative safety and efficacy of extended-release bupivacaine formulations, although more data are needed to define their indications and dosing 4.
• Bupivacaine/meloxicam PR significantly reduced postoperative pain and opioid consumption relative to bupivacaine hydrochloride and placebo in patients undergoing certain surgeries 5.
• However, a systematic review of randomized clinical trials found that liposomal bupivacaine did not demonstrate significant pain relief compared to placebo or active agents in 74.58% of studies, and did not show a reduction in opioid consumption in 85.71% of studies evaluating narcotic use 6.

Clinical Use

• Exparel is used for postoperative pain management, particularly in multimodal analgesia regimens 3, 7.
• It is approved for infiltration of the tissues during surgery and for interscalene nerve block analgesia following shoulder surgery 4.
• Bupivacaine/meloxicam PR is approved in the EU and the USA to treat postoperative pain, and is used as the foundation of a scheduled non-opioid multimodal analgesia regimen 5.