Skip to main content

General

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].

Adverse Reactions Reported in All Wound Infiltration Clinical Studies

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 retention, urinary incontinence, vision blurred, tinnitus, drug hypersensitivity, and hypersensitivity.

Neurological and Cardiac Adverse Reactions Reported in All Wound Infiltration Clinical Studies

In the EXPAREL wound 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 Wound Infiltration Clinical Studies

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.

Table 1: Treatment-Emergent Adverse Reactions (TEAE) with an Incidence Greater than or Equal to 2%: Placebo-Controlled Studies

System Organ Class
Preferred Term
STUDY 1a STUDY 2b
EXPAREL 8 mL/1.3 % (106 mg)
(N=97)
n (%)
Placebo
(N=96)
n (%)
EXPAREL 20 mL/1.3% (266 mg)
(N=95)
n (%)
Placebo
(N=94 )
n (%)
Any TEAE 53 (54.6) 59 (61.5) 10 (10.5) 17 (18.1)
Gastrointestinal Disorders 41 (42.3) 38 (39.6) 7 (7.4) 13 (13.8)
  Nausea 39 (40.2) 36 (37.5) 2 (2.1) 1 (1.1)
  Vomiting 27 (27.8) 17 (17.7) 2 (2.1) 4 (4.3)
  Constipation 2 (2.1) 1 (1.0) 2 (2.1) 2 (2.1)
  Anal Hemorrhage 0 (0.0) 0 (0.0) 3 (3.2) 4 (4.3)
  Painful Defecation 0 (0.0) 0 (0.0) 2 (2.1) 5 (5.3)
  Rectal Discharge 0 (0.0) 0 (0.0) 1 (1.1) 3 (3.2)
Nervous System Disorders 20 (20.6) 30 (31.3) 0 (0.0) 0 (0.0)
  Dizziness 11 (11.3) 25 (26.0) 0 (0.0) 0 (0.0)
  Headache 5 (5.2) 8 (8.3) 0 (0.0) 0 (0.0)
  Somnolence 5 (5.2) 1 (1.0) 0 (0.0) 0 (0.0)
  Syncope 2 (2.1) 0 (0.0) 0 (0.0) 0 (0.0)
Skin And Subcutaneous Tissue Disorders 8 (8.2) 7 (7.3) 0 (0.0) 0 (0.0)
  Pruritus Generalized 5 (5.2) 6 (6.3) 0 (0.0) 0 (0.0)
  Pruritus 3 (3.1) 1 (1.0) 0 (0.0) 0 (0.0)
Investigations 5 (5.2) 3 (3.1) 4 (4.2) 3 (3.2)
  Alanine Aminotransferase Increased 3 (3.1) 3 (3.1) 1 (1.1) 0 (0.0)
  Aspartate Aminotransferase Increased 3 (3.1) 2 (2.1) 0 (0.0) 0 (0.0)
  Blood Creatinine Increased 2 (2.1) 0 (0.0) 0 (0.0) 0 (0.0)
  Body Temperature Increased 0 (0.0) 0 (0.0) 3 (3.2) 3 (3.2)
General Disorders And Administration Site Conditions 4 (4.1) 0 (0.0) 1 (1.1) 1 (1.1)
  Feeling Hot 2 (2.1) 0 (0.0) 0 (0.0) 0 (0.0)
  Pyrexia 2 (2.1) 0 (0.0) 1 (1.1) 1 (1.1)
Infections And Infestations 2 (2.1) 1 (1.0) 0 (0.0) 0 (0.0)
  Fungal Infection 2 (2.1) 1 (1.0) 0 (0.0) 0 (0.0)
Injury, Poisoning And Procedural Complications 2 (2.1) 0 (0.0) 0 (0.0) 0 (0.0)
  Post Procedural Swelling 2 (2.1) 0 (0.0) 0 (0.0) 0 (0.0)
Metabolism And Nutrition Disorders 2 (2.1) 2 (2.1) 0 (0.0) 0 (0.0)
  Decreased Appetite 2 (2.1) 2 (2.1) 0 (0.0) 0 (0.0)
a Study 1: Bunionectomy
b Study 2: Hemorrhoidectomy
At each level of summation (overall, system organ class, preferred term), patients are only counted once. Preferred terms are included where at least 2% of patients reported the event in any treatment group.
TEAE = treatment-emergent adverse event.