Bupivacaine and Meloxicam

ZYNRELEF is indicated in adults for postsurgical analgesia for up to 72 hours after: soft tissue surgical procedures orthopedic surgical procedures – foot and ankle procedures – other orthopedic surgical procedures (e.g., total joint arthroplasty) in which direct exposure to articular cartilage is avoided ZYNRELEF is indicated in adults for postsurgical analgesia for up to 72 hours after: soft tissue surgical procedures orthopedic surgical procedures – foot and ankle procedures – other orthopedic surgical procedures (e.g., total joint arthroplasty) in which direct exposure to articular cartilage is avoided Limitations of Use Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large 4 or more level spinal, and head and neck procedures.

ZYNRELEF is a fixed-dose combination of bupivacaine and meloxicam. Bupivacaine Local anesthetics block the generation and the conduction of nerve impulses presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone. Meloxicam The mechanism of action of meloxicam, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2). Meloxicam is a potent inhibitor of prostaglandin synthesis in vitro.

ZYNRELEF is intended for single-dose administration only. Administer ZYNRELEF via instillation only. The toxic effects of local anesthetics are additive. Avoid additional use of local anesthetics within 96 hours following administration of ZYNRELEF. ZYNRELEF should only be prepared and administered with the components provided in the ZYNRELEF kit. ZYNRELEF is applied without a needle into the surgical site following final irrigation and suction and prior to suturing. – The recommended dose of ZYNRELEF is up to a maximum dose of 400 mg/12 mg (14 mL). See Full Prescribing Information for important preparation and administration instructions, dose selection, and compatibility considerations.

ZYNRELEF is contraindicated in: Patients with a known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to any local anesthetic agent of the amide-type, NSAIDs, or to any of the other components of ZYNRELEF. Patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients. Patients undergoing obstetrical paracervical block anesthesia. The use of bupivacaine in this technique has resulted in fetal bradycardia and death. Patients undergoing coronary artery bypass graft (CABG) surgery.

Boxed warning: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. ZYNRELEF is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Dose-Related Toxicity: Monitor cardiovascular and respiratory vital signs and patient's state of consciousness after application of ZYNRELEF. When using ZYNRELEF with other local anesthetics, overall local anesthetic exposure must be considered through 72 hours. Hepatotoxicity: If abnormal liver tests persist or worsen, perform a clinical evaluation of the patient. Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure.

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 Gastrointestinal Bleeding, Ulceration, and Perforation Dose-Related Toxicity Hepatotoxicity Hypertension Heart Failure and Edema Renal Toxicity and Hyperkalemia Anaphylactic Reactions Chondrolysis Methemoglobinemia Exacerbation of Asthma Related to Aspirin Sensitivity Serious Skin Reactions Drug Reaction with Eosinophilia and Systemic Toxicity (DRESS) Fetal Toxicity Hematologic Toxicity Most common adverse reactions (incidence ≥5%) are: Soft tissue procedures: vomiting. Orthopedic procedures: constipation and headache.

Drugs that Interfere with Hemostasis (e.g., warfarin, aspirin, SSRIs/SNRIs): Monitor patients for bleeding who are concomitantly taking ZYNRELEF with drugs that interfere with hemostasis. ACE Inhibitors, Angiotensin Receptor Blockers (ARBs), or Beta-Blockers: Concomitant use with ZYNRELEF may diminish the antihypertensive effect of these drugs. Monitor blood pressure. ACE Inhibitors and ARBs: Concomitant use with ZYNRELEF in elderly, volume-depleted, or those with renal impairment may result in deterioration of renal function. In such high-risk patients, monitor for signs of worsening renal function. Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effect.

Store ZYNRELEF kits at 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C to 30°C (59°F to 86°F). If ZYNRELEF vials are removed from the kit, store them at controlled room temperature. Protect from moisture and light. Protect from light during storage.