Bupivacaine and meloxicam

What Bupivacaine and meloxicam is used for

Quoted from the “Indications and Usage” section of the FDA-approved label.

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 …

— FDA label: Zynrelef, Heron Therapeutics, Inc., effective April 20, 2026. Read the full label on DailyMed →

Label quoted: the one for the most common form (solution, infiltration), Zynrelef, Heron Therapeutics, Inc.; it covers 2 products in the FDA NDC Directory. The side effects, interactions, dosage and pregnancy quotes below come from this same label.

This page is not medical advice. Talk to your doctor or pharmacist before you start, stop or change any medicine.

Boxed warning

A boxed warning (“black box”) is the FDA’s strongest warning on a drug label, for serious or life-threatening risks.

This label has a boxed warning. Its heading: WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS. Read it on the full label →

Bupivacaine and meloxicam boxed warning: what the label says

Quoted from the boxed warning of the FDA-approved label.

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS See full prescribing information for complete 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.

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This risk may occur early in treatment and may increase with duration of use (5.1) ZYNRELEF is contraindicated in the setting of coronary artery bypass graft (CABG) surgery (4, 5.1) NSAIDs cause an increased risk of serious gastrointestinal (GI) 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 for serious GI events (5.2) Cardiovascular Thrombotic Events 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 [see Warnings and Precautions (5.1)]. ZYNRELEF is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4) and Warnings and Precautions (5.1)]. Gastrointestinal Bleeding, Ulceration, and Perforation NSAIDs cause an increased risk of serious gastrointestinal (GI) 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 for serious GI events [see Warnings and Precautions (5.2)].

— FDA label: Zynrelef, Heron Therapeutics, Inc., effective April 20, 2026. Read the full label on DailyMed →

Bupivacaine and meloxicam side effects

Quoted from the “Adverse Reactions” section of the FDA-approved label. Tell your doctor about any side effect that worries you.

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 …

— FDA label: Zynrelef, Heron Therapeutics, Inc., effective April 20, 2026. This is part of the section. Read the full label on DailyMed →

Bupivacaine and meloxicam drug interactions

Quoted from the “Drug Interactions” section of the FDA-approved label. Tell your pharmacist about every medicine, vitamin and herbal product you take.

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 (7.2). ACE Inhibitors, Angiotensin Receptor Blockers (ARBs), or Beta-Blockers: Concomitant use with ZYNRELEF may diminish the antihypertensive effect of these drugs. Monitor blood pressure (7.2).

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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 (7.2). Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effect (7.2). 7.1 Bupivacaine Drug Interactions In clinical studies, other local anesthetics (including ropivacaine and lidocaine) have been administered before, during, or after application of ZYNRELEF without evidence of local anesthetic systemic toxicity. Administration of ZYNRELEF with other formulations of local anesthetics, including bupivacaine liposome injectable suspension, has not been studied [see Warnings and Precautions (5.3)]. The toxic effects of local anesthetics are additive. Avoid additional use of local anesthetics within 96 hours following administration of ZYNRELEF. If co-administration cannot be avoided, monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [see Dosage and Administration (2.1), Warnings and Precautions (5.1) and Overdosage (10)]. Patients who are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics (Table 5). Table 5. Examples of Drugs Associated with Methemoglobinemia Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine 7.2 Meloxicam Drug Interactions See Table 6 for clinically significant drug interactions with meloxicam. Table 6. Clinically Significant Drug Interactions with Meloxicam Drugs that Interfere with Hemostasis Clinical Impact: Meloxicam and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of meloxicam and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone.

— FDA label: Zynrelef, Heron Therapeutics, Inc., effective April 20, 2026. This is part of the section. Read the full label on DailyMed →

Bupivacaine and meloxicam dosage

Quoted from the “Dosage and Administration” section of the FDA-approved label. Your own dose is the one your doctor prescribes: do not change it on your own.

ZYNRELEF is intended for single-dose administration only (2.1). 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 (2.1). ZYNRELEF should only be prepared and administered with the components provided in the ZYNRELEF kit (2.1).

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ZYNRELEF is applied without a needle into the surgical site following final irrigation and suction and prior to suturing (2.1). – The recommended dose of ZYNRELEF is up to a maximum dose of 400 mg/12 mg (14 mL) (2.4). See Full Prescribing Information for important preparation and administration instructions, dose selection, and compatibility considerations (2.2, 2.3, 2.4, 2.5). 2.1 Important Dosage and Administration Information ADMINISTER ZYNRELEF VIA INSTILLATION ONLY. ZYNRELEF should not be administered via the following routes. – Epidural – Intrathecal – Intravascular – Intra-articular [see Warnings and Precautions (5.10), Nonclinical Toxicology (13.2)] – Regional nerve blocks – Pre-incisional or pre-procedural locoregional anesthetic techniques. ZYNRELEF is intended for single-dose administration only. As there is a potential risk of severe, life-threatening adverse reactions associated with the administration of bupivacaine, ZYNRELEF should be administered in a setting where trained personnel and equipment are available to promptly treat patients who show evidence of neurologic or cardiac toxicity [see Overdosage (10)]. The toxic effects of local anesthetics are additive. Avoid additional use of local anesthetics within 96 hours following administration of ZYNRELEF. Avoid intravascular administration of ZYNRELEF. Convulsions and cardiac arrest have occurred following accidental intravascular injection of bupivacaine and other amide-containing products. Limit exposure to articular cartilage due to the potential risk of chondrolysis [see Warnings and Precautions (5.11)]. ZYNRELEF is a viscous solution supplied as a kit consisting of a single-dose glass vial, and the following sterile components: Luer lock syringe(s), a vented vial spike or vial access needle, Luer lock cone-shaped applicator(s), and syringe tip cap(s). ZYNRELEF should only be prepared and administered with the components provided in the ZYNRELEF kit. See the ZYNRELEF Instructions for Use included in the kit for complete administration instructions with illustrations. The contents of the ZYNRELEF vial are sterile. The vial exterior is not sterile. Follow your facility's standard operating procedures regarding aseptic drug preparation. Each ZYNRELEF vial contains overfill to compensate for residual amounts that remain in the vial, vented vial spike or vial access needle, Luer lock applicator, and syringe(s) during drug withdrawal and administration. ZYNRELEF is applied without a needle into the surgical site after placement of implant(s) (if applicable), following final irrigation and suctioning, and prior to suturing of each layer, when multiple tissue layers are involved.

— FDA label: Zynrelef, Heron Therapeutics, Inc., effective April 20, 2026. This is part of the section. Read the full label on DailyMed →

Bupivacaine and meloxicam in pregnancy

Quoted from the pregnancy part of the FDA-approved label. Ask your doctor before you take any medicine while pregnant or planning a pregnancy.

Risk Summary There are no available human data on use of ZYNRELEF in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. However, there are available data on the individual components of ZYNRELEF, bupivacaine and meloxicam.

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Bupivacaine The available data on bupivacaine use in pregnant women for epidural anesthesia (excluding paracervical block) are insufficient to draw conclusions about a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are no adequate and well-controlled studies with bupivacaine in pregnant women. In animal studies, embryo-fetal lethality was noted when bupivacaine was administered subcutaneously to pregnant rabbits during organogenesis at a comparable bupivacaine dose level of 400 mg at the maximum recommended human dose (MRHD) of ZYNRELEF. Decreased pup survival was observed in a rat pre- and post-natal developmental study (dosing from implantation through weaning) at a comparable bupivacaine dose to the MRHD (see Data). Based on animal data, pregnant women should be advised of the potential risks to a fetus. Meloxicam Use of NSAIDs, including ZYNRELEF, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of ZYNRELEF use between about 20 and 30 weeks of gestation and avoid ZYNRELEF use at about 30 weeks of gestation and later in pregnancy (see Clinical Considerations, Data). Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including ZYNRELEF, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies, embryofetal death was observed in rats and rabbits treated during the period of organogenesis with meloxicam at oral doses equivalent to 0.8 and 8 times, respectively, the meloxicam dose level of 12 mg at the MRHD of ZYNRELEF. Increased incidence of septal heart defects was observed in rabbits treated throughout embryogenesis with meloxicam at an oral dose equivalent to 97 times the MRHD. In pre- and post-natal reproduction studies, there was an increased incidence of dystocia, delayed parturition, and decreased offspring survival at 0.1 times the MRHD. No malformations were observed in rats and rabbits treated with meloxicam during organogenesis at an oral dose equivalent to 3.2 and 32 times, respectively, the MRHD (see Data).

— FDA label: Zynrelef, Heron Therapeutics, Inc., effective April 20, 2026. This is part of the section. Read the full label on DailyMed →

When Bupivacaine and meloxicam should not be used

Quoted from the “Contraindications” section of the FDA-approved label.

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 [see Warnings and Precautions (5.9, 5.14)]. Patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs.

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Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.9)]. Patients undergoing obstetrical paracervical block anesthesia. The use of bupivacaine in this technique has resulted in fetal bradycardia and death [see Use in Specific Populations (8.1)]. Patients undergoing coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1)]. ZYNRELEF is contraindicated for: 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 (4) 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 (4) Patients undergoing obstetrical paracervical block anesthesia (4) Patients undergoing coronary artery bypass graft (CABG) surgery (4)

— FDA label: Zynrelef, Heron Therapeutics, Inc., effective April 20, 2026. Read the full label on DailyMed →

Bupivacaine and meloxicam overdose

Quoted from the “Overdosage” section of the FDA-approved label. If someone may have taken too much, call Poison Help at 1-800-222-1222 (or 911 in an emergency).

No data are available with regard to overdose of ZYNRELEF. Findings related to the individual active substances are listed below. 10.1 Bupivacaine Clinical Presentation Acute emergencies from local anesthetics are generally related to high plasma concentrations encountered during therapeutic use of local anesthetics or to unintended intravascular injection of local anesthetic solution [see (Warnings and Precautions (5.3) and Adverse Reactions (6)].

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Following administration of ZYNRELEF (400 mg/12 mg) by instillation, a highest individual maximum plasma concentration (C max) of bupivacaine of 1830 ng/mL was reported. No apparent bupivacaine-related systemic toxicity was observed. Signs and symptoms of overdose include CNS symptoms (dizziness, sensory and visual disturbances, and eventually convulsions) and cardiovascular effects (that range from hypertension and tachycardia to myocardial depression, hypotension, bradycardia, and asystole). Plasma levels of bupivacaine associated with toxicity can vary. Although concentrations of 2,000 to 4,000 ng/mL have been reported to elicit early subjective CNS symptoms of bupivacaine toxicity, symptoms of toxicity have been reported at levels as low as 800 ng/mL. Management of Local Anesthetic Overdose At the first sign of change, oxygen should be administered. The first step in the management of convulsions, as well as underventilation or apnea, consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress the circulation when administered intravenously. Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, small increments of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as diazepam) may be administered intravenously. The clinician should be familiar, prior to the use of anesthetics, with these anticonvulsant drugs. Supportive treatment of circulatory depression may require administration of intravenous fluids and, when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine to enhance myocardial contractile force). If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias, and cardiac arrest. If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted. Endotracheal intubation, employing drugs, and techniques familiar to the clinician, may be indicated after initial administration of oxygen by mask if difficulty is encountered in the maintenance of a patent airway or if prolonged ventilatory support (assisted or controlled) is indicated. 10.2 Meloxicam Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care. Gastrointestinal bleeding has occurred.

— FDA label: Zynrelef, Heron Therapeutics, Inc., effective April 20, 2026. This is part of the section. Read the full label on DailyMed →

Forms and how it is given

Same medicine, other forms and combinations

Prescription medicine pages on this site that share an active ingredient with this one, from the FDA NDC Directory. A combination is a different medicine: ask your pharmacist before you switch.

Other medicines with one of these active ingredients

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• Meloxicam, rizatriptanSymbravo · 1 product

Companies that list this medicine

Labelers in the FDA NDC Directory: the company named on the package (maker or distributor), with the number of prescription products.

• Heron Therapeutics, Inc.2 products

FDA approval history

• NDA: New Drug Application: how a new (usually brand-name) medicine is approved.

Shortage status

The FDA drug shortage list does not show these products.

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Recalls

From FDA enforcement reports, matched by the product’s NDC code. A recall usually covers specific lots only: check the lot number on your package and ask your pharmacist. Do not stop a medicine on your own.

1. August 2, 2022 · Class III · Terminated · D-1335-2022

   Defective Delivery System: An incorrect 10 mL (12 mL) Luer (slip) syringe packaged in one lot of Zynrelef 400 mg/12 mg kit

   Zynrelef (bupivacaine and meloxicam), 400 mg bupivacaine and 12 mg meloxicam single dose application, packaged in a kit, Rx only, Manufactured for Heron Therapeutics, Inc., San Diego, CA, NDC 47426-301-02 — HERON THERAPEUTICS, INC.

Official identifiers

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Sources

1. FDA-approved label on DailyMed (National Library of Medicine) — Zynrelef, Heron Therapeutics, Inc., effective April 20, 2026; via openFDA, FDA data exported October 30, 2026, retrieved October 31, 2026
2. NDC Directory (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
3. Drugs@FDA (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
4. Drug recall enforcement reports (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 27, 2026, retrieved October 31, 2026
5. Drug shortages (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026

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