Nonnarcotic analgesics:

Indications for: ZYNRELEF

To produce postsurgical analgesia for up to 72 hours after foot and ankle, small to medium open abdominal, and lower extremity total joint arthroplasty surgical procedures.

Limitations of Use:

Safety and efficacy have not been established in highly vascular surgeries (eg, intrathoracic, large multilevel spinal, head and neck procedures).

Adult Dosage:

See full labeling. For single-dose administration only. Apply only to tissue layers below the skin incision. Foot and ankle (eg, bunionectomy): apply 60mg/1.8mg (up to 2.3mL) to proximal and distal ends of the wound. Small to medium open abdominal (eg, open inguinal herniorrhaphy): close the peritoneum (if applicable), then apply 300mg/9mg (up to 10.5mL) above and below the fascial repair. Lower extremity total joint arthroplasty (eg, total knee arthroplasty): apply 400mg/12mg (up to 14mL) directly to the joint capsule, the anteromedial tissues and periosteum, and the anterolateral tissues and periosteum after placement of the components.

Children Dosage:

Not established.

ZYNRELEF Contraindications:

Aspirin allergy. Obstetrical paracervical block anesthesia. Coronary artery bypass graft surgery.

Boxed Warning:

Risk of serious cardiovascular and gastrointestinal events.

ZYNRELEF Warnings/Precautions:

Should be administered where trained personnel and resuscitative equipment are readily available. Avoid epidural, intrathecal, intravascular, intra-articular, regional nerve blocks, pre-incisional or pre-procedural locoregional anesthetic techniques. Increased risk of serious cardiovascular events (including MI, stroke). Avoid in recent MI, severe heart failure; if necessary, monitor. Increased risk of serious GI adverse events (including inflammation, bleeding, ulceration, perforation). History of ulcer disease and/or GI bleeding. Cardiovascular dysfunction (eg, hypotension, heart block); monitor closely for BP, HR, and ECG changes. Monitor cardiovascular and respiratory vital signs, and patient’s state of consciousness after administration. Evaluate if signs/symptoms of liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, others). Hypertension; monitor BP. Dehydration. Hypovolemia. Advanced renal disease: not recommended; if needed, monitor. Hyperkalemia. Limit exposure to articular cartilage due to potential risk of chondrolysis. Risk of methemoglobinemia (esp. in G6PD deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants <6 months of age, concurrent exposure to oxidizing agents or metabolites); monitor closely and discontinue any oxidizing agents if occurs. Pre-existing asthma. Coagulation disorders. May mask signs of infection or fever. Renal impairment (mild to moderate): consider dose reduction; (severe): not recommended; (on hemodialysis): do not exceed max dose or use with other meloxicam-containing products. Hepatic impairment (moderate to severe): monitor for toxicity; (severe): only use if benefits outweigh risks. Poor CYP2C9 metabolizers: monitor and consider dose reduction. Debilitated. Elderly. Labor & delivery. May be associated with a reversible delay in ovulation in females of reproductive potential. Pregnancy (avoid during ≥30 weeks gestation): increased risk of premature closure of the fetal ductus arteriosus; (20–30 weeks gestation): may cause fetal renal dysfunction/oligohydramnios; if treatment needed, limit dose and duration of use. Nursing mothers.

ZYNRELEF Classification:

Local anesthetic (amide-type) + NSAID (oxicam).

ZYNRELEF Interactions:

Avoid additional local anesthetics within 96hrs after Zynrelef administration; if unavoidable, monitor for neurologic and cardiovascular effects. Increased risk of methemoglobinemia when concurrently exposed to nitrates/nitrites, local anesthetics, antineoplastic agents, antibiotics, antimalarials, anticonvulsants, others (eg, acetaminophen, metoclopramide, quinine, sulfasalazine). Increased risk of GI bleed with anticoagulants, antiplatelets, oral corticosteroids, SSRIs, SNRIs, smoking, alcohol, or prolonged NSAID therapy; monitor. Avoid concomitant with other NSAIDs or salicylates (eg, aspirin, diflunisal, salsalate); if additional NSAID or salicylate is indicated, monitor for toxicity. May antagonize, or increase risk of renal failure with diuretics (eg, loop or thiazides), ACE inhibitors, ARBs, or β-blockers; monitor closely. Potentiates digoxin; monitor. May potentiate lithium, methotrexate, cyclosporine; monitor for toxicity. Concomitant with pemetrexed may increase risk of pemetrexed-associated myelosuppression, renal, and GI toxicity.

Adverse Reactions:

Constipation, vomiting, headache, nausea, hypertension; cardiovascular thrombotic events, GI ulcer/bleed, hepatotoxicity, renal toxicity, edema, CNS toxicity (eg, restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth/lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, drowsiness), serious skin reactions (eg, SJS, TEN), DRESS (evaluate if signs/symptoms develop), anemia, anaphylactic reactions, chondrolysis (with unapproved intra-articular infusion).

Generic Drug Availability:


How Supplied:

Kit—1 (vial + supplies)