Exparel

• 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 is for single administration only (
  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.
  ).
• 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 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.
  ,
  2.5 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.
  ).
• Do
  not
  dilute EXPAREL with water or other hypotonic solutions (
  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.
  ).
• 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 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)]

    .
    ).
  • 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 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)]

    .
    ).
  • Interscalene brachial plexus nerve block in adults is 133 mg (
    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)]

    .
    ).
  • Sciatic nerve block in the popliteal fossa in adults is 133 mg (
    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)]

    .
    ).
  • 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 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)]

    .
    ).
• For all these nerve blocks, administer additional analgesics, which may include other immediate-release local anesthetics, as appropriate (
  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)]

  .
  ).
• See Full Prescribing Information for important preparation and administration instructions and compatibility considerations (
  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.
  ).

EXPAREL (bupivacaine liposome injectable suspension) is a white to off-white, milky aqueous suspension that is available in the following vial sizes:

• 1.3% (266 mg/20 mL) (13.3 mg/mL) single-dose vial
• 1.3% (133 mg/10 mL) (13.3 mg/mL) single-dose vial