Dosing and uses of Exparel (bupivacaine liposome)
Adult dosage forms and strengths
injectable suspension
- 1.3% (13.3mg/mL)
Postsurgical Analgesia
Indicated for single-dose infiltration into surgical site to produce postsurgical analgesia
Recommended dose based on size of the surgical site and volume required to cover the area; not to exceed 266 mg (20 mL)
As general guidance in selecting the proper dosing for the planned surgical site, 2 examples of dosing are provided below
Bunionectomy
- 106 mg (8 mL) once via infiltration of surgical site
- Infiltrate 7 mL into tissues surrounding osteotomy and 1 mL into subcutaneous tissue
Hemorrhoidectomy
- 266 mg (20 mL) once via infiltration of surgical site
- Dilute 20 mL with 10 mL of saline, for a total of 30 mL, and divide the mixture into six 5 mL aliquots
- Perform the anal block by visualizing the anal sphincter as a clock face and slowly infiltrating one aliquot to each of the even numbers
Dosage modifications
Renal impairment
- Bupivacaine is substantially excreted by the kidney
- Risk of toxicity may be greater in patients with impaired renal function; use caution
Hepatic impairment
- Amide-type local anesthetics (eg, bupivacaine) are metabolized by the liver
- Severe hepatic impairment: Greater risk of developing toxic plasma concentrations; use caution
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Exparel (bupivacaine liposome) adverse (side) effects
>10%
Nausea (2.1-40.2%)
Vomiting (2.1-27.8%)
1-10%
Dizziness (6.2%)
Tachycardia (3.9%)
Headache (3.8%)
Somnolence (2.1%)
Bradycardia (1.6%)
Hypoesthesia (1.5%)
Lethargy (1.3%)
Warnings
Contraindications
Obstetrical paracervical block anesthesia; use of bupivacaine for paracervical block has resulted in fetal bradycardia and death
Cautions
For single administration only (see Administration)
Not interchangeable with other forms of bupivacaine (see Administration)
For infiltrative use only; do not use for epidural, intrathecal, regional nerve blocks, or intravascular or intra-articular administration
Has not been evaluated for patients younger than 18 years, pregnant or nursing patients
Use only in a setting where trained personnel and equipment are available to promptly treat patients who show evidence of neurological or cardiac toxicity
Monitor cardiovascular/neurological status and vital signs during and after injection
CNS reactions characterized by excitation and/or depression, restlessness, anxiety, dizziness, tinnitus, blurred vision, tremors, or convulsions; other CNS effects may include nausea, vomiting, chills, and miosis
Toxic blood concentrations may depress cardiac conductivity and excitability that leads to AV block, ventricular arrhythmias, and cardiac arrest; additionally, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure
Allergic-type reactions are rare; cross-sensitivity to other amide-type local anesthetics reported
Chondrolysis: Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been postmarketing reports of chondrolysis in patients receiving such infusions
Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, use cautiously with hepatic disease; greater risk for toxic plasma concentrations with severe hepatic disease
Not for administration within 96 hours of administering other bupivacaine formulations
Pregnancy and lactation
Pregnancy category: C; bupivacaine is contraindicated for obstetrical paracervical block anesthesia
Lactation: Excreted to some extent in human breast milk; potential exposure to nursing infant
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Exparel (bupivacaine liposome)
Mechanism of action
Local anesthetic; blocks generation and conduction of nerve impulses presumably by increasing the electrical excitation threshold in the nerve, by slowing nerve impulse propagation, and by reducing the rate of action potential rise
Liposomal suspension of bupivacaine
Absorption
Absorption rate dependent on total dose, administration route, and administration site vascularity
Duration: Up to 96 hours
Peak Plasma Time: 2 hr (bunionectomy); 0.5 hr (hemorrhoidectomy)
Peak Plasma Concentration: 166 ng/mL (bunionectomy); 867 ng/mL (hemorrhoidectomy)
AUC: 5864-7105 hr•ng/mL (bunionectomy); 16,867-18,289 hr•ng/mL
Distribution
Protein Bound: 95%
Widely distributed to some extent to all body tissues; high concentrations found in highly perfused organs (eg, liver, lungs, heart, brain)
Metabolism
Metabolized primarily by the liver via conjugation with glucuronic acid
Metabolites: ~5% converted to the major metabolite, pipecolylxylidine (PPX)
Elimination
Half-life: 34.1 hr (bunionectomy); 23.8 hr (hemorrhoidectomy)
Excretion: Mainly as metabolites in the urine
Administration
General Instructions
Inject slowly into soft tissue via infiltration surgical site with frequent aspiration to check for blood and minimize the risk of intravascular injection
For single-dose infiltration 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 bupivacaine liposome
Do not exceed 266 mg (20 mL, 1.3% of undiluted drug)
Administer with a ≥25-gauge bore needle
Not to exceed 266 mg (20 mL, 1.3% of undiluted drug)
Do not administer if product discolored
Do not administer if the vial has been frozen as reflected by the temperature indicator or exposed to high temperature (>40°C or 104°F) for an extended period
Can be administered undiluted or diluted up to 0.89 mg/mL (ie, 1:14 dilution by volume) with preservative-free 0.9% sterile saline for injection
Invert vial multiple times to resuspend particles immediately prior to withdrawing drug from vial; multiple inversions may be necessary to resuspend if particles have settled
Use diluted suspensions within 4 hr of preparation in a syringe
Compatibility Considerations
Incompatabilities: Nonbupivacaine based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from Exparel if administered together locally
Bupivacaine liposome may follow lidocaine administration after waiting at least 20 minutes
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 simultaneous use of both forms of bupivacaine are additive and their administration should be used with caution including monitoring for neurologic and cardiovascular effects related to toxicity
Using Exparel followed by other bupivacaine formulations has not been studied in clinical trials; formulations of bupivacaine other than Exparel should not be administered within 96 hr following administration of ExpareL
When a topical antiseptic (eg, povidone iodine) is applied, the site should be allowed to dry before bupivacaine liposome is administered into the surgical site; bupivacaine liposome should not be allowed to come into contact with antiseptics such as povidone iodine in solution
Handling
Visually inspect vials before use
Do not filter
Do not heat before use
Do not autoclave
Storage
Store refrigerated between 2-8°C (36-46°F)
May be held at controlled room temperature of 20-25°C (68-77°F) for up to 1 month in sealed, intact (unopened) vials
Vials should not be re-refrigerated
Should not be frozen as reflected by the temperature indicator or exposed to high temperatures (>40°C 104°F]) for an extended period
Do not administer if suspected of having been frozen as reflected by the temperature indicator or exposed to high temperatures (freeze indicator turns from green to white when exposed to freezing temperatures)
