General MedicationsINFILTRATIONHigh Alert

EXPAREL

BUPIVACAINE

Standard Dose

2 DOSAGE AND ADMINISTRATION EXPAREL is for single administration only ( 2.1 ). EXPAREL is not substitutable with other bupivacaine products even if the strength is the same. Therefore, it is not possible to convert a dose from other bupivacaine products to an EXPAREL dose and vice versa ( 2.1 , 2.5 ). Do not dilute EXPAREL with water or other hypotonic solutions ( 2.1 ). The recommended dose of EXPAREL for: Local infiltration in adults is up to a maximum dose of 266 mg. See Full Prescribing Information for guidance on dose selection ( 2.2 ). Local infiltration in pediatric patients aged 6 to less than 17 years is 4 mg/kg, up to a maximum of 266 mg ( 2.2 ). Interscalene brachial plexus nerve block in adults is 133 mg ( 2.3 ). Sciatic nerve block in the popliteal fossa in adults is 133 mg ( 2.3 ). Adductor canal block in adults is 133 mg (10 mL) admixed with 50 mg (10 mL) 0.5% bupivacaine HCl, for a total volume of 20 mL ( 2.3 ). For all these nerve blocks, administer additional analgesics, which may include other immediate-release local anesthetics, as appropriate ( 2.3 ). See Full Prescribing Information for important preparation and administration instructions and compatibility considerations ( 2.4 , 2.5 ). 2.1 Important Dose, Preparation, and Administration Instructions EXPAREL is for single administration only. EXPAREL is not substitutable with other bupivacaine products even if the strength is the same. Therefore, it is not possible to convert a dose from other bupivacaine products to an EXPAREL dose and vice versa. Do not dilute EXPAREL with water or other hypotonic agents, as it will result in disruption of the liposomal particles. Do not administer EXPAREL if it is suspected that the vial has been frozen or exposed to high temperature (greater than 40°C or 104°F) for an extended period. Inspect EXPAREL visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer EXPAREL if the product is discolored. Do not heat or autoclave before use. Do not filter during administration. 2.2 Recommended Dose for Local Analgesia via Infiltration Local Analgesia via Infiltration in Adults The recommended dose of EXPAREL for local infiltration in adults is up to a maximum dose of 266 mg, and is based on the following factors: Size of the surgical site Volume required to cover the area Individual patient factors that may impact the safety of an amide local anesthetic As general guidance in selecting the proper EXPAREL dose for local infiltration in adults, two examples are provided [see Clinical Studies (14.2) ]. In adult patients undergoing: Bunionectomy, a total of 106 mg (8 mL) of EXPAREL was administered, with 7 mL infiltrated into the tissues surrounding the osteotomy, and 1 mL infiltrated into the subcutaneous tissue. Hemorrhoidectomy, a total of 266 mg (20 mL) of EXPAREL was diluted with 10 mL of saline, for a total of 30 mL, divided into six 5 mL aliquots, injected by visualizing the anal sphincter as a clock face and slowly infiltrating one aliquot to each of the even numbers to produce a field block. Local Analgesia via Infiltration in Pediatric Patients The recommended dose of EXPAREL for one-time infiltration in pediatric patients, aged 6 to less than 17 years, is 4 mg/kg (up to a maximum of 266 mg), and is based upon two studies of pediatric patients undergoing either spine surgery or cardiac surgery [see Use in Specific Populations (8.4) ] . 2.3 Recommended Dose for Regional Analgesia The maximum recommended dose of EXPAREL via perineural use for interscalene brachial plexus nerve block, sciatic nerve block in the popliteal fossa, and adductor canal block is 133 mg. For all these nerve blocks, administer additional analgesics, which may include other immediate-release local anesthetics, as appropriate (for example, Mayo field block for bunionectomy, infiltration between the popliteal artery and capsule of the knee (IPACK) block for total knee arthroplasty). Regional Analgesia via Interscalene Brachial Plexus Nerve Block in Adults The recommended dose of EXPAREL for interscalene brachial plexus nerve block in adults is 133 mg and is based upon one study of patients undergoing either total shoulder arthroplasty or rotator cuff repair [see Clinical Studies (14.3) ] . Regional Analgesia via Sciatic Nerve Block in the Popliteal Fossa in Adults The recommended dose of EXPAREL for sciatic nerve block in the popliteal fossa in adults is 133 mg and is based upon one study of patients undergoing bunionectomy [see Clinical Studies (14.3) ] . Regional Analgesia via Adductor Canal Block in Adults The recommended dose of EXPAREL for adductor canal block in adults is 133 mg (10 mL) admixed with 50 mg (10 mL) 0.5% bupivacaine HCl, for a total volume of 20 mL, and is based upon one study of patients undergoing total knee arthroplasty [see Clinical Studies (14.3) ] . 2.4 Preparation and Administration Instructions Invert vials of EXPAREL multiple times to re-suspend the particles immediately prior to withdrawal from the vial. Administer EXPAREL (1) undiluted or (2) diluted to increase volume up to a final concentration of 0.89 mg/mL (i.e., 1:14 dilution by volume) with 0.9% preservative-free Sodium Chloride Injection or lactated Ringer's solution. Use diluted EXPAREL within 4 hours of preparation in a syringe. Administer EXPAREL with a 25 gauge or larger bore needle to maintain the structural integrity of the liposomal bupivacaine particles. Administer EXPAREL slowly via infiltration or perineural use with frequent aspiration to check for blood and minimize the risk of inadvertent intravascular injection. Discard unused portion. 2.5 Compatibility Considerations Some physicochemical incompatibilities exist between EXPAREL and certain other drugs. Direct contact of EXPAREL with these drugs results in a rapid increase in free (unencapsulated) bupivacaine, altering EXPAREL characteristics and potentially affecting the safety and efficacy of EXPAREL. Therefore, admixing EXPAREL with other drugs prior to administration is not recommended [see Drug Interactions (7) ] . Non-bupivacaine based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more. Bupivacaine HCl administered together with EXPAREL may impact the pharmacokinetic and/or physicochemical properties of EXPAREL, and this effect is concentration dependent. Therefore, bupivacaine HCl and EXPAREL may be administered simultaneously in the same syringe, and bupivacaine HCl may be injected immediately before EXPAREL if the ratio of the milligram dose of bupivacaine HCl solution to EXPAREL does not exceed 1:2. The toxic effects of these drugs are additive, and their administration should be used with caution including monitoring for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [see Warnings and Precautions (5.1) and Overdosage (10) ] . When a topical antiseptic such as povidone iodine (e.g., Betadine) is applied, the site should be allowed to dry before EXPAREL is administered into the site. EXPAREL should not be allowed to come into contact with antiseptics such as povidone iodine in solution. Studies conducted with EXPAREL demonstrated that the most common implantable materials (polypropylene, PTFE, silicone, stainless steel, and titanium) are not affected by the presence of EXPAREL any more than they are by saline. None of the materials studied had an adverse effect on EXPAREL.

Max Dose

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Primary Use

1 INDICATIONS AND USAGE EXPAREL is indicated to produce postsurgical: Local analgesia via infiltration in patients aged 6 years and older Regional analgesia via an interscalene brachial plexus nerve block in adults Regional analgesia via a sciatic nerve block in the popliteal fossa in adults Regional analgesia via an adductor canal block in adults EXPAREL contains bupivacaine, an amide local anesthetic, and is indicated to produce postsurgical: Local analgesia via infiltration in patients aged 6 years and older ( 1 ).

Summary

Regional analgesia via an interscalene brachial plexus nerve block in adults ( 1 ).

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE EXPAREL is indicated to produce postsurgical: Local analgesia via infiltration in patients aged 6 years and older Regional analgesia via an interscalene brachial plexus nerve block in adults Regional analgesia via a sciatic nerve block in the popliteal fossa in adults Regional analgesia via an adductor canal block in adults EXPAREL contains bupivacaine, an amide local anesthetic, and is indicated to produce postsurgical: Local analgesia via infiltration in patients aged 6 years and older ( 1 ). Regional analgesia via an interscalene brachial plexus nerve block in adults ( 1 ). Regional analgesia via a sciatic nerve block in the popliteal fossa in adults ( 1 ). Regional analgesia via an adductor canal block in adults ( 1 ). Limitations of Use The safety and effectiveness of EXPAREL have not been established to produce postsurgical regional analgesia via other nerve blocks besides an interscalene brachial plexus nerve block, a sciatic nerve block in the popliteal fossa, or an adductor canal block. Limitations of Use The safety and effectiveness of EXPAREL have not been established to produce postsurgical regional analgesia via other nerve blocks besides an interscalene brachial plexus nerve block, a sciatic nerve block in the popliteal fossa, or an adductor canal block. Dosage and administration 2 DOSAGE AND ADMINISTRATION EXPAREL is for single administration only ( 2.1 ). EXPAREL is not substitutable with other bupivacaine products even if the strength is the same. Therefore, it is not possible to convert a dose from other bupivacaine products to an EXPAREL dose and vice versa ( 2.1 , 2.5 ). Do not dilute EXPAREL with water or other hypotonic solutions ( 2.1 ). The recommended dose of EXPAREL for: Local infiltration in adults is up to a maximum dose of 266 mg. See Full Prescribing Information for guidance on dose selection ( 2.2 ). Local infiltration in pediatric patients aged 6 to less than 17 years is 4 mg/kg, up to a maximum of 266 mg ( 2.2 ). Interscalene brachial plexus nerve block in adults is 133 mg ( 2.3 ). Sciatic nerve block in the popliteal fossa in adults is 133 mg ( 2.3 ). Adductor canal block in adults is 133 mg (10 mL) admixed with 50 mg (10 mL) 0.5% bupivacaine HCl, for a total volume of 20 mL ( 2.3 ). For all these nerve blocks, administer additional analgesics, which may include other immediate-release local anesthetics, as appropriate ( 2.3 ). See Full Prescribing Information for important preparation and administration instructions and compatibility considerations ( 2.4 , 2.5 ). 2.1 Important Dose, Preparation, and Administration Instructions EXPAREL is for single administration only. EXPAREL is not substitutable with other bupivacaine products even if the strength is the same. Therefore, it is not possible to convert a dose from other bupivacaine products to an EXPAREL dose and vice versa. Do not dilute EXPAREL with water or other hypotonic agents, as it will result in disruption of the liposomal particles. Do not administer EXPAREL if it is suspected that the vial has been frozen or exposed to high temperature (greater than 40°C or 104°F) for an extended period. Inspect EXPAREL visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer EXPAREL if the product is discolored. Do not heat or autoclave before use. Do not filter during administration. 2.2 Recommended Dose for Local Analgesia via Infiltration Local Analgesia via Infiltration in Adults The recommended dose of EXPAREL for local infiltration in adults is up to a maximum dose of 266 mg, and is based on the following factors: Size of the surgical site Volume required to cover the area Individual patient factors that may impact the safety of an amide local anesthetic As general guidance in selecting the proper EXPAREL dose for local infiltration in adults, two examples are provided [see Clinical Studies (14.2) ]. In adult patients undergoing: Bunionectomy, a total of 106 mg (8 mL) of EXPAREL was administered, with 7 mL infiltrated into the tissues surrounding the osteotomy, and 1 mL infiltrated into the subcutaneous tissue. Hemorrhoidectomy, a total of 266 mg (20 mL) of EXPAREL was diluted with 10 mL of saline, for a total of 30 mL, divided into six 5 mL aliquots, injected by visualizing the anal sphincter as a clock face and slowly infiltrating one aliquot to each of the even numbers to produce a field block. Local Analgesia via Infiltration in Pediatric Patients The recommended dose of EXPAREL for one-time infiltration in pediatric patients, aged 6 to less than 17 years, is 4 mg/kg (up to a maximum of 266 mg), and is based upon two studies of pediatric patients undergoing either spine surgery or cardiac surgery [see Use in Specific Populations (8.4) ] . 2.3 Recommended Dose for Regional Analgesia The maximum recommended dose of EXPAREL via perineural use for interscalene brachial plexus nerve block, sciatic nerv

Monitoring

• 5 WARNINGS AND PRECAUTIONS Monitor cardiovascular status, neurological status, and vital signs during and after injection of EXPAREL ( 5.1 ).
• Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, use EXPAREL cautiously in patients with hepatic disease.
• Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations ( 5.1 ).
• Methemoglobinemia: Cases of methemoglobinemia have been reported in association with local anesthetic use ( 5.1 ).

Interaction Notes

• 7 DRUG INTERACTIONS The toxic effects of local anesthetics are additive and concomitant use should be used with caution including monitoring for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) , and Overdosage (10) ] .
• Avoid additional use of local anesthetics within 96 hours following administration of EXPAREL.
• Patients who are administered local anesthetics, including EXPAREL, may be at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine Lidocaine or other non-bupivacaine local anesthetics : Do not admix with EXPAREL.
• EXPAREL may be administered at least 20 minutes or more following local administration of lidocaine ( 7 ).