Exparel

EXPAREL is indicated for administration into the surgical site to produce postsurgical analgesia. EXPAREL has not been studied for use in patients younger than 18 years of age.

Since bupivacaine liposome is used as a single dose, it does not have a daily dosing schedule.

Exparel is a prescription medication used to prevent post-surgical pain.

Exparel belongs to a group of drugs called local anesthetics. These work by blocking the generation of nerve impulses that cause pain.

Exparel is a version of bupivacaine that is encapsulated in a fat delivery (liposomal) system that breaks down slowly in the body, which allows the extended release of the anesthetic over 48 to 96 hours.

This medication is available in an injectable form to be infiltrated directly into the surgical site by a healthcare professional.

Common side effects of Exparel include nausea, constipation, and vomiting.

Serious side effects have been reported with bupivacaine. See the “Bupivacaine Precautions” section.

Common side effects of bupivacaine include the following:

• Nausea
• Constipation
• Vomiting
• Chills

This is not a complete list of bupivacaine side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Before taking bupivacaine, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to bupivacaine or to any of its ingredients
• have or have had liver problems
• have or have had heart problems
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• topical (applied to the skin) medicine that contains lidocaine.

This list is not complete. Other drugs may interact with bupivacaine liposome, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Use Exparel as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Your doctor will give this medicine.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

Exparel is intended for single-dose administration only.

The recommended dose of Exparel 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
• Maximum dose of 266 mg (20 mL)

As general guidance in selecting the proper dosing for the planned surgical site, two examples of dosing are provided. One example of the recommended dose comes from a study in patients undergoing bunionectomy. A total of 8 mL (106 mg) was administered as 7 mL of Exparel infiltrated into the tissues surrounding the osteotomy, and 1 mL infiltrated into the subcutaneous tissue.

Another example comes from a study of patients undergoing hemorrhoidectomy. A total of 20 mL (266 mg) 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.

Injection Instructions

Exparel should be injected slowly into soft tissues of the surgical site with frequent aspiration to check for blood and minimize the risk of intravascular injection.

• Exparel is intended for single-dose administration only.
• Different formulations of bupivacaine are not bioequivalent even if the milligram strength is the same. Therefore, it is not possible to convert dosing from any other formulations of bupivacaine to Exparel.
• Exparel should be administered with a 25 gauge or larger bore needle.
• The maximum dosage of Exparel should not exceed 266 mg (20 mL, 1.3% of undiluted drug).
• Exparel can be administered undiluted or diluted to increase volume up to a final concentration of 0.89 mg/mL (i.e. 1:14 dilution by volume) with normal (0.9%) saline or lactated Ringer’s solution.
• Vials of Exparel should be inverted multiple times to re-suspend the particles immediately prior to withdrawal from the vial
• Diluted suspensions of Exparel should be used within 4 hours of preparation in a syringe.
• Do not administer Exparel if the product is discolored.
• 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.

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 as long as 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 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 surgical 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.

When administered in recommended doses and concentrations, bupivacaine HCl does not ordinarily produce irritation or tissue damage and does not cause methemoglobinemia.

Non-Interchangeability with Other Formulations of Bupivacaine

Different formulations of bupivacaine are not bioequivalent even if the milligram dosage is the same. Therefore, it is not possible to convert dosing from any other formulations of bupivacaine to Exparel and vice versa.

Liposomal encapsulation or incorporation in a lipid complex can substantially affect a drug's functional properties relative to those of the unencapsulated or nonlipid-associated drug. In addition, different liposomal or lipid-complexed products with a common active ingredient may vary from one another in the chemical composition and physical form of the lipid component. Such differences may affect functional properties of these drug products. Do not substitute.

Bupivacaine Adverse Reactions

The most commonly encountered acute adverse experiences to bupivacaine and all amide-type local anesthetics that demand immediate counter-measures are related to the central nervous and cardiovascular systems.

High plasma concentrations of bupivacaine can occur from overdosage, unintended intravascular injection, or accumulation of bupivacaine in plasma secondary to decreased hepatic metabolic degradation of the drug or diminished plasma protein binding capacity due to acidosis, pathologically lowered plasma protein production, or competition with other drugs for protein binding sites. Although rare, some individuals have a lower tolerance to and are supersensitive to bupivacaine and other amide-type local anesthetics and may rapidly develop signs of toxicity at low doses [See Overdosage (10)].

Clinical Trial Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The safety of Exparel was evaluated in 10 randomized, double-blind, local administration into the surgical site clinical studies involving 823 patients undergoing various surgical procedures. Patients were administered a dose ranging from 66 to 532 mg of Exparel. In these studies, the most common adverse reactions (incidence greater than or equal to 10%) following Exparel administration were nausea, constipation, and vomiting.

The common adverse reactions (incidence greater than or equal to 2% to less than 10%) following Exparel administration were pyrexia, dizziness, edema peripheral, anemia, hypotension, pruritus, tachycardia, headache, insomnia, anemia postoperative, muscle spasms, hemorrhagic anemia, back pain, somnolence, and procedural pain.

The less common/rare adverse reactions (incidence less than 2%) following Exparel administration were chills, erythema, bradycardia, anxiety, urinary retention, pain, edema, tremor, dizziness postural, paresthesia, syncope, incision site edema, procedural hypertension, procedural hypotension, procedural nausea, muscular weakness, neck pain, pruritus generalized, rash pruritic, hyperhidrosis, cold sweat, urticaria, bradycardia, palpitations, sinus bradycardia, supraventricular extrasystoles, ventricular extrasystoles, ventricular tachycardia, hypertension, pallor, anxiety, confusional state, depression, agitation, restlessness, hypoxia, laryngospasm, apnea, respiratory depression, respiratory failure, body temperature increased, blood pressure increased, blood pressure decreased, oxygen saturation decreased, urinary incontinence, vision blurred, tinnitus, drug hypersensitivity, and hypersensitivity.

Neurological and Cardiac Adverse Reactions

In the Exparel surgical site infiltration studies, adverse reactions with an incidence greater than or equal to 1% in the Nervous System Disorders system organ class following Exparel administration were dizziness (6.2%), headache (3.8%), somnolence (2.1%), hypoesthesia (1.5%), and lethargy (1.3%). The adverse reactions with an incidence greater than or equal to 1% in the Cardiac Disorders system organ class following Exparel administration were tachycardia (3.9%) and bradycardia (1.6%).

Adverse Reactions Reported in Placebo-Controlled Trials

Adverse reactions with an incidence greater than or equal to 2% reported by patients in clinical studies comparing 8 mL Exparel 1.3% (106 mg) to placebo and 20 mL Exparel 1.3% (266 mg) to placebo are shown in Table 1.

Exparel (bupivacaine liposome injectable suspension) is available in single-use vials for infiltration.

      20 mL single use vial, 1.3% (13.3 mg/mL) (NDC 65250-266-20) packaged in cartons of 10 (NDC 65250-266-09) and cartons of 4 (NDC 65250-266-04)

      10 mL single use vial, 1.3% (13.3 mg/mL) (NDC 65250-133-10) packaged in cartons of 10 (NDC-65250-133-09) and cartons of 4 (NDC 65250-133-04)

Storage

Exparel vials should be stored refrigerated between 2°C to 8°C (36°F to 46°F). Exparel may be held at a controlled room temperature of 20°C to 25°C (68°F to 77°F) for up to 30 days in sealed, intact (unopened) vials. Vials should not be re-refrigerated.

Exparel should not be frozen or exposed to high temperatures (greater than 40°C or 104°F) for an extended period. Do not administer Exparel if it is suspected of having been frozen or exposed to high temperatures. Do not use the vial if the stopper is bulging.

Handling

• Vials of Exparel should be inverted to re-suspend the particles immediately prior to withdrawal from the vial. Multiple inversions may be necessary to re-suspend the particles if the contents of the vial have settled.
• Vials should be visually inspected before use.
• Do not filter.
• Do not heat before use.
• Do not autoclave.
• Following withdrawal from the vial, Exparel may be stored at controlled room temperature of 20°C to 25°C (68°F to 77°F) for up to 4 hours prior to administration.
• Discard any unused portion in an appropriate manner.

Exparel is given as an injection placed into an area near your surgical incision. You will receive this injection in a hospital or surgical setting.

Exparel can have long-lasting or delayed effects. For at least 4 days (96 hours) after your surgery, tell any doctor or dentist who treats you that you recently received a bupivacaine liposome injection.

Call your doctor if you have joint pain or stiffness, or weakness in any part of your body that occurs after your surgery, even months later.