Complete adverse effect profile including incidence rates and management
Important Safety Information
This is not a complete list of all possible side effects. Contact your healthcare provider if you experience any unexpected symptoms. For serious or life-threatening side effects, seek emergency medical attention immediately.
6 ADVERSE REACTIONS The following serious adverse reactions have been associated with bupivacaine HCl or meloxicam and are discussed in greater detail in other sections of the labeling: Cardiovascular System Reactions [see Warnings and Precautions (5.1 , 5.4) ] Gastrointestinal Bleeding, Ulceration, and Perforation [see Warnings and Precautions (5.2) ] Dose-Related Toxicity [see Warnings and Precautions (5.3) ] Hepatotoxicity [see Warnings and Precautions (5.5) ] Hypertension [see Warnings and Precautions (5.6) ] Heart Failure and Edema [see Warnings and Precautions (5.7) ] Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.8) ] Anaphylactic Reactions [see Warnings and Precautions (5.9) ] Chondrolysis [see Warnings and Precautions (5.11) ] Methemoglobinemia [see Warnings and Precautions (5.12) ] Exacerbation of Asthma Related to Aspirin Sensitivity [see Warnings and Precautions (5.13) ] Serious Skin Reactions [see Warnings and Precautions (5.14) ] Drug Reaction with Eosinophilia and Systemic Toxicity (DRESS) [see Warnings and Precautions (5.15) ] Fetal Toxicity [see Warnings and Precautions (5.16) ] Hematologic Toxicity [see Warnings and Precautions (5.17) ] Most common adverse reactions (incidence ≥5%) are: Soft tissue procedures: vomiting ( 6.1 ).
Orthopedic procedures: constipation and headache ( 6.1 ).
To report SUSPECTED ADVERSE REACTIONS, contact Heron Therapeutics, Inc.
at 1-844-437-6611 and www.ZYNRELEF.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials 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 ZYNRELEF has been evaluated in a total of 1627 patients undergoing various surgical procedures across 14 clinical studies including 7 randomized, double-blind, bupivacaine- and placebo-controlled and saline placebo-controlled studies designed to investigate ZYNRELEF to reduce postoperative pain for 72 hours and the need for opioid analgesics, of whom 1183 received ZYNRELEF by instillation.
Patients treated with ZYNRELEF ranged in age from 18 to 85 years (median age 51 years), with 53.0% female, 82.1% White, 13.7% African-American, and 4.3% all other races.
Common Adverse Reactions The safety of ZYNRELEF has been evaluated in 1064 patients who received ZYNRELEF in single doses up to 400 mg/12 mg via instillation into the surgical site, including 533 patients undergoing a soft tissue surgical procedure (herniorrhaphy, abdominoplasty, augmentation mammoplasty, or Cesarean section) and 531 patients undergoing an orthopedic surgical procedure (bunionectomy, total knee arthroplasty, total shoulder arthroplasty, or lumbar spinal surgery).
The most common adverse reactions (incidence greater than or equal to 5% and higher than placebo) following ZYNRELEF administration among patients undergoing soft tissue procedures was vomiting and among patients undergoing orthopedic procedures were constipation and headache.
The safety of ZYNRELEF as part of a scheduled, non-opioid multimodal analgesic regimen including 1 or more other NSAIDs has been evaluated in a total of 473 patients undergoing soft tissue procedures or orthopedic procedures.
5 WARNINGS AND PRECAUTIONS Dose-Related Toxicity : Monitor cardiovascular and respiratory vital signs and patient's state of consciousness after application of ZYNRELEF ( 5.3 ).
When using ZYNRELEF with other local anesthetics, overall local anesthetic exposure must be considered through 72 hours ( 5.3 ).
Hepatotoxicity : If abnormal liver tests persist or worsen, perform a clinical evaluation of the patient ( 5.5 ).
Hypertension : Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs.
Monitor blood pressure ( 5.6 , 7 ).
Like all medications, Zynrelef can cause side effects. However, not everyone who takes this medication will experience them. Many side effects are dose-dependent and may improve as your body adjusts to the medication. Others may require dose adjustment or medical attention.
Contact your healthcare provider promptly if you experience:
Seek immediate emergency medical care if you experience signs of: