ZYNRELEF KIT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYNRELEF KIT (ZYNRELEF KIT).
Zynrelef is a fixed-dose combination of bupivacaine and meloxicam. Bupivacaine blocks sodium channels in neuronal membranes, inhibiting nerve impulse conduction. Meloxicam inhibits cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis and inflammation.
| Metabolism | Bupivacaine is primarily metabolized by the liver via conjugation with glucuronic acid; the major metabolite is pipecoloxylidine. Meloxicam is extensively metabolized in the liver by CYP2C9 (major) and CYP3A4 (minor) to four inactive metabolites. |
| Excretion | Renal: 70% unchanged; biliary/fecal: 20% as metabolites; 10% other |
| Half-life | Terminal half-life of bupivacaine (component) is 3.5 hours; for meloxicam (component) is 20 hours. Clinical context: bupivacaine half-life prolonged in hepatic impairment; meloxicam half-life prolonged in elderly (up to 25 hours) |
| Protein binding | Bupivacaine: 95% bound to alpha-1-acid glycoprotein; meloxicam: 99% bound to albumin |
| Volume of Distribution | Bupivacaine: Vd 1.0 L/kg (extensive tissue distribution); meloxicam: Vd 0.15 L/kg (confined to plasma) |
| Bioavailability | Local infiltration: 100% (site of action); not administered systemically |
| Onset of Action | Local infiltration: within 5 minutes for surgical analgesia |
| Duration of Action | Local infiltration: up to 72 hours of postsurgical analgesia (single dose) |
| Molecular Weight | 342.7 |
Instillation into the surgical site: 20 mL (300 mg bupivacaine and 9.3 mg meloxicam) as a single dose.
| Dosage form | SOLUTION, EXTENDED RELEASE |
| Renal impairment | Avoid use in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²). No dose adjustment recommended for mild to moderate impairment (eGFR 30-89 mL/min/1.73 m²). |
| Liver impairment | Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). No dose adjustment recommended for mild to moderate impairment (Child-Pugh Class A or B). |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required, but elderly patients may be more sensitive to systemic effects; use caution with concomitant NSAIDs or anticoagulants. |
| 1st trimester | Avoid unless clearly needed; no adequate well-controlled studies in pregnant women. Fetal risk cannot be ruled out. |
| 2nd trimester | Use only if potential benefit justifies potential risk to fetus; consider gestational age and severity of condition. |
| 3rd trimester | Avoid during labor and delivery; may prolong gestation or inhibit uterine contractions. Use only if clearly indicated. |
Clinical note
Comprehensive clinical and safety monograph for ZYNRELEF KIT (ZYNRELEF KIT).
| Placental transfer | Bupivacaine crosses the placenta rapidly via passive diffusion; meloxicam crosses the placenta with measurable fetal levels. Degree of transfer is moderate to high for both components. |
| Breastfeeding | Bupivacaine and meloxicam are excreted into human milk in small amounts. Use with caution; monitor infant for sedation, apnea, or gastrointestinal effects. Consider discontinuing breastfeeding or the drug. |
■ FDA Black Box Warning
WARNING: CARDIOVASCULAR RISK WITH NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs); AND WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS. 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. NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk.
| Serious Effects |
Hypersensitivity to bupivacaine, meloxicam, or any componentKnown sulfite allergy (contains sodium metabisulfite)Obstetric paracervical blockSevere hepatic impairmentActive peptic ulcer or GI bleedingAdvanced renal diseaseHistory of asthma, urticaria, or allergic-type reaction after aspirin or NSAIDsCABG surgery perioperative pain
| Precautions | Cardiovascular thrombotic events; Gastrointestinal bleeding, ulceration, and perforation; Hepatotoxicity; Hypertension; Heart failure and edema; Renal toxicity; Anaphylactic reactions; Serious skin reactions; Hematologic toxicity; Central nervous system effects (e.g., convulsions, cardiac arrest) with bupivacaine; Risk of chondrolysis with intra-articular use; Risk of nerve damage with regional block; Risk of methemoglobinemia; Use in patients with known or suspected sulfite sensitivity. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | ZYNRELEF (bupivacaine and meloxicam) is a local anesthetic and NSAID combination. For bupivacaine, not teratogenic in animals; limited human data. For meloxicam, NSAIDs are associated with premature closure of the ductus arteriosus starting at 30 weeks gestation, oligohydramnios, and increased risk of miscarriage. First trimester: potential risk of miscarriage and malformations (meloxicam). Second trimester: avoid prolonged use due to oligohydramnios risk. Third trimester: contraindicated after 30 weeks due to fetal ductus arteriosus constriction. |
| Fetal Monitoring | Monitor for hypotension, arrhythmias, and local anesthetic systemic toxicity in mother. Fetal heart rate monitoring during and after administration if near term. Monitor for signs of NSAID-related complications: check amniotic fluid index, ductus arteriosus patency (echocardiography) if gestational age >30 weeks. Monitor maternal renal function and platelet count. |
| Fertility Effects | Meloxicam as an NSAID may impair fertility in women of reproductive potential by inhibition of ovulation (reversible on discontinuation). Bupivacaine has no known direct effect on fertility. No fertility studies with the combination. |
| Food/Dietary | No specific food interactions; avoid alcohol consumption as it may increase the risk of gastrointestinal bleeding and renal impairment. |
| Clinical Pearls | ZYNRELEF (bupivacaine and meloxicam) is an NSAID-containing local anesthetic; avoid concomitant use with other NSAIDs, anticoagulants, or drugs affecting renal function. Monitor for signs of neuraxial toxicity if used near the spine. Not for intravenous or epidural administration. Do not use in patients with known NSAID hypersensitivity, renal impairment, or active peptic ulcer disease. |
| Patient Advice | ZYNRELEF is a single-dose medication given during surgery for pain relief lasting up to 72 hours. · Do not take additional NSAIDs (e.g., ibuprofen, naproxen) while this drug is active without consulting your doctor. · Seek immediate medical attention if you experience signs of infection, bleeding, or allergic reaction at the surgical site. · Inform your healthcare provider about all medications you take, especially blood thinners, aspirin, or other pain relievers. · This drug may impair kidney function; stay hydrated and report decreased urination or swelling. |