EXPAREL Post-tonsillectomy Clinical Trial

Bupivacaine liposome injectable suspension 1.3% is a non-narcotic long acting local
anesthetic agent that is also used to produce postsurgical analgesia after infiltration into
the surgical site. The bupivacaine liposome injectable suspension drug delivery system allows
slow release of the 1.3% bupivacaine suspension which extends its analgesic effect up to 96
hours. The objective for this proposed study is to evaluate the use of bupivacaine liposome
injectable suspension as an adjunct to the standard of care medication bupivacaine
hydrochloride (HCl) 0.25% (2.5 mg/mL) with epinephrine (5 mcg/mL) to manage pain experienced
by adult patients after bilateral palatine tonsillectomy.

Tonsillectomy is one of the most commonly performed surgical procedures in the United States.
In 2006, there were approximately 680,000 ambulatory surgery visits for chronic diseases of
the tonsils and adenoids in children and adults. Indications for tonsillectomy in the adult
population include recurrent pharyngitis, chronic tonsillitis, and obstructive pathology.
Tonsillectomy is often associated with severe postoperative pain, which can result in
prolonged poor oral intake, dehydration, and the need for high dose narcotics. In severely
dehydrated patients, epithelial shedding and necrosis of soft tissues at the surgical site
can lead to postoperative complications such as bleeding, delayed healing, and severe pain.

Increasingly, the quality of surgical care is evaluated by examining readmission and
complication rates. In a cross-sectional analysis of ambulatory surgery and hospital
databases from New York, Florida, Iowa, and California for 2010, investigators identified a
revisit rate of 11.3% in 7,748 adult patients who underwent bilateral tonsillectomy.
Additionally, the investigators noted the primary diagnoses at first revisit were bleeding
(41.3%), acute pain (22.1%), and fever/dehydration (13.2%). Improving pain control after
tonsillectomy has the potential to decrease patient morbidity and the financial burden to the
health care system.

Investigators have examined a number of methods to reduce postoperative pain, including
variation of surgical technique; preoperative, intraoperative, and postoperative medications;
and pre-incisional or post-excisional injections of local anesthetics. Several studies have
demonstrated short-term improvement in pain control with local infiltration of bupivacaine
into the surgical site. Pre-incisional and/or post-excisional injection of bupivacaine HCl is
now commonly used for pain management in patients undergoing tonsillectomy. However, one of
the limitations of local anesthetics such as bupivacaine HCl is the relatively short duration
of action, about 3 - 6 hours.

Pharmaceutical companies have recently developed new technologies for drug delivery, such as
long acting carriers of local anesthetic using multi-vesicular liposomes to increase drug
duration of action. One such formulation is bupivacaine liposome injectable suspension with
an average duration of action of 72 hours. In a clinical review of the literature, Tong,
Kaye, and Urman noted that use of liposomal bupivacaine decreased narcotic requirements and
improved pain ratings in patients who underwent mammoplasty, knee arthroplasty,
hemorrhoidectomy, and inguinal hernia repair.

Currently to investigators' best knowledge, there is no study in published literature that
evaluated the use of bupivacaine liposome injectable suspension for pain management in adults
after tonsillectomy. At present, there are two completed clinical trials registered in the
National Clinical Trials database. One small scale study was done to characterize the
pharmacokinetic profile of single dose bupivacaine liposome injectable suspension infused
intraoperatively for prolonged analgesia in 12 adults undergoing tonsillectomy. In another
study, the investigator examined post-operative use of liposomal bupivacaine for pain
management compared to no post-operative treatment in 33 adult patients. Preliminary results
from the randomized control trial indicated that there was a significant difference in pain
ratings between the bupivacaine liposome injectable suspension active comparator and the no
treatment group on the day of surgery.

For this proposed study, the aim is to evaluate the use of bupivacaine liposome injectable
suspension to manage pain experienced by adult patients after tonsillectomy. In this study
the investigators will examine whether Exparel (bupivacaine liposome injectable suspension
1.3%—13.3 mg/mL) when used as a post-excision adjunct to the standard of care bupivacaine HCl
0.25% (2.5 mg/mL) with Epinephrine (5mcg/mL), will decrease the patient's post-tonsillectomy
experience of pain intensity, especially for the first three days after surgery, and
correspondingly reduce the requirement for pain medications.

Inclusion Criteria:

- Scheduled to undergo bilateral palatine tonsillectomy as the only procedure

Exclusion Criteria:

- Presence of severe systemic disease

- Presence of coagulation disorders

- Current or previous history of analgesic dependence

- Allergy to any of the drugs used in the study

- Women pregnant or lactating, or women planning to become pregnant

- Presence of hearing loss

- Presence of cardiovascular comorbidities

- Presence of hepatic comorbidities

- Presence of kidney comorbidities

- Presence of cognitive disabilities