Xaracoll

Xaracoll Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions have been reported and described in the Warnings section in the labeling:

• Dose-Related Toxicity [see WARNINGS AND PRECAUTIONS]
• Methemoglobinemia [see WARNINGS AND PRECAUTIONS]

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 XARACOLL was evaluated in 11 clinical studies, including two Phase 3 double-blind, placebo implant-controlled studies in patients undergoing open, unilateral inguinal hernia repair. Overall, 612 patients were treated with a single dose of XARACOLL, total dose ranged from 100 mg to 300 mg bupivacaine HCl. Patients treated with XARACOLL ranged in age from 18 of 85 years (median age 51 years), with 88% male, 88% White, 9% African-American, and 3% all other races.

Across the XARACOLL drug development program, which included evaluations in various surgery models, there was one patient death reported in the placebo implant treatment group, and 16 patients who experienced one or more serious adverse events; 11 patients in the XARACOLL treatment group and 5 patients in the placebo implant or comparator treatment groups. Serious adverse reactions reported in the XARACOLL treatment group included wound infection and seroma. There was a single patient who experienced signs and symptoms consistent with local anesthetic systemic toxicity (LAST) approximately four hours after administration of an early formulation of the bupivacaine collagen implant, 150 mg, during bladder sling surgery. LAST treatment included administration of lipid emulsion and surgical removal of the XARACOLL implants.

The most common adverse reactions (incidence greater than or equal to 2% and higher than placebo implant) following XARACOLL administration were dysgeusia, headache, scrotal swelling, tremor, pyrexia, vision blurred, and seroma. Common incision site adverse reactions (incidence greater than or equal to 2% and higher in either the XARACOLL or placebo implant groups compared to non-implant comparator treatment groups) were swelling, pain, other complication, post-procedural discharge, erythema, dehiscence, and inflammation.

Adverse Reactions Reported In Phase 3 Placebo-Controlled Trials

There were 619 patients who underwent open inguinal hernia repair in the two Phase 3 studies. Patients received general anesthesia intra-operatively, and a standard acetaminophen regimen, in addition to intravenous and oral morphine as needed, post-operatively. The most common adverse reactions (incidence greater than or equal to 2% and higher than placebo implants) following XARACOLL administration were incision site swelling, dysgeusia, headache, tremor, vision blurred, seroma, scrotal swelling, pyrexia, hypoesthesia oral, and post-procedural discharge, shown in Table 1.

Table 1: Adverse Reactions (ARs) with Incidence Greater Than or Equal to 2% and Greater Than Placebo Reported in the Phase 3 Placebo-controlled Studies

Postmarketing Experience

The following adverse reactions from voluntary reports have been reported with various formulations of bupivacaine, administered via different routes and for different indications. Because many of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions to bupivacaine are characteristic of those associated with other amide-type local anesthetics. A major cause of adverse reactions to this group of drugs is excessive plasma levels, which may be due to overdosage, unintentional intravascular injection, or slow metabolic degradation.

The most commonly encountered acute adverse reactions that demand immediate counter-measures were related to the CNS and the cardiovascular system. These adverse reactions were generally dose-related and due to high plasma levels, which may have resulted from overdosage, rapid absorption from the injection site, diminished tolerance, or from unintentional intravascular injection of the local anesthetic solution.

Nervous System Disorders

Adverse reactions were characterized by excitation and/or depression of the central nervous system and included restlessness, anxiety, dizziness, tinnitus, blurred vision, tremors, convulsions, drowsiness, unconsciousness, respiratory arrest, nausea, vomiting, chills, pupillary constriction.

Neurological effects following routes of administration other than epidural or caudal have included persistent anesthesia, paresthesia, weakness, and paralysis, all with slow, incomplete, or no recovery.

The incidence of adverse neurologic reactions associated with the use of local anesthetics may be related to the total dose of local anesthetic administered and are also dependent upon the particular drug used, the route of administration, and the physical status of the patient.

Cardiac Disorders

High doses have led to high plasma levels and related depression of the myocardium, decreased cardiac output, heart block, hypotension, bradycardia, ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation, and cardiac arrest.

Immune System Disorders

Allergic-type reactions have occurred as a result of sensitivity to bupivacaine or to other formulation ingredients. These reactions were characterized by signs such as urticaria, pruritus, erythema, angioneurotic edema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and severe hypotension. Cross sensitivity among members of the amide-type local anesthetic group has been reported.

Read the entire FDA prescribing information for Xaracoll (Bupivacaine Hydrochloride Implant)