Version July 2025
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. Meloxicam is contraindicated during the perioperative setting of coronary artery bypass graft (CABG) surgery.
NSAIDs cause an increased risk of serious 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.
Note: Avoid use of local anesthetics within 96 hours following administration.
Analgesia, postsurgical:
Orthopedic procedure instillation:
Bunionectomy: Up to 2.3 mL (bupivacaine 60 mg/meloxicam 1.8 mg) as a single dose.
Knee or shoulder, total arthroplasty: Up to 14 mL (bupivacaine 400 mg/meloxicam 12 mg) as a single dose.
Spinal surgery, 1 to 3 level: Up to 7 mL (bupivacaine 200 mg/meloxicam 6 mg) as a single dose.
Soft tissue procedure instillation:
Abdominoplasty: Up to 14 mL (bupivacaine 400 mg/meloxicam 12 mg) as a single dose.
Cesarean delivery: Up to 14 mL (bupivacaine 400 mg/meloxicam 12 mg) as a single dose.
Inguinal herniorrhaphy: Up to 10.5 mL (bupivacaine 300 mg/meloxicam 9 mg) as a single dose.
Mammoplasty, augmentation: Up to 7 mL per side (total of bupivacaine 400 mg/meloxicam 12 mg) as a single dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate impairment: There are no specific dosage adjustments provided in the manufacturer's labeling; consider reduced dosage.
Severe impairment: There are no specific dosage adjustments provided in the manufacturer's labeling (has not been studied); use not recommended.
Mild impairment: No dosage adjustment necessary.
Moderate impairment: No dosage adjustment necessary; consider more frequent monitoring for toxicities in patients with moderate impairment.
Severe impairment: There are no specific dosage adjustments provided in the manufacturer's labeling; use only if benefits outweigh risks. Risk of toxicity may be increased in patients with severe impairment; consider more frequent monitoring for toxicities in patients with severe impairment.
Refer to adult dosing; consider reduced dosage. Unless alternative agents are ineffective and a gastroprotective agent can be administered, avoid short-term scheduled use in combination with corticosteroids, anticoagulants, or antiplatelet agents or chronic use with or without medications that increase risk for bleeding (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see individual agents.
>10%:
Cardiovascular: Edema (incision site: 17%), hypertension (19%)
Dermatologic: Erythema of skin (incision site: 13%)
Gastrointestinal: Constipation (24%), nausea (50%), vomiting (26%)
Nervous system: Dizziness (22%), headache (7% to 14%)
Miscellaneous: Fever (14%)
1% to 10%:
Cardiovascular: Bradycardia (8% to 9%), hypotension (5%)
Dermatologic: Abnormal skin odor (8%), cellulitis (incision site: 4%), hyperhidrosis (5%), pruritus (7%)
Gastrointestinal: Dysgeusia (9%)
Hematologic & oncologic: Anemia (5%), leukocytosis (7%)
Infection: Infection (incision site: 3%)
Neuromuscular & skeletal: Muscle twitching (6%)
Miscellaneous: Wound dehiscence (4%), wound healing impairment (6%)
Frequency not defined:
Cardiovascular: Acute myocardial infarction, coronary thrombosis
Gastrointestinal: Gastrointestinal hemorrhage, gastrointestinal inflammation, gastrointestinal perforation, gastrointestinal ulcer, intestinal perforation
Nervous system: Cerebrovascular accident
Postmarketing: Miscellaneous: Postoperative wound complication (necrosis)
Hypersensitivity (eg, anaphylactic reactions, serious skin reactions) to bupivacaine or any local anesthetic agent of the amide-type, nonsteroidal anti-inflammatory drugs (NSAIDs) including meloxicam, or any component of the formulation; history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; patients undergoing obstetrical paracervical block anesthesia or coronary artery bypass graft (CABG) surgery.
Concerns related to adverse effects:
• Anaphylactoid reactions: Anaphylactoid reactions may occur, even in patients without prior nonsteroidal anti-inflammatory drug (NSAID) exposure; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Use is contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy.
• Cardiovascular events: NSAIDs cause an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including myocardial infarction (MI) and stroke. Risk may occur early during treatment, with higher doses, and may increase with duration of use; the risk of cardiovascular thrombotic events following single-dose application is unknown. Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of serious cardiovascular thrombotic events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors. New onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to angiotensin-converting-enzyme [ACE] inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor BP; use with caution in patients with hypertension. May cause sodium and fluid retention; use with caution in patients with edema. Avoid use in patients with heart failure when possible (Heidenreich 2022). Avoid use in patients with recent MI unless benefits outweigh risk of cardiovascular thrombotic events. To reduce risk of cardiovascular events, do not exceed recommended dose. Bupivacaine-containing products have been associated with rare occurrences of arrhythmias, cardiac arrest, and death.
• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.
• GI events: Avoid use in patients with active GI bleeding. In patients with a history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis (Strate 2016). Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors [SSRIs]), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in elderly or debilitated patients. When used concomitantly with aspirin, a substantial increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (ACCF/ACG/AHA [Bhatt 2008]).
• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time. Patients with coagulation disorders or who are receiving anticoagulants, antiplatelets, SSRIs, or serotonin and norepinephrine reuptake inhibitors should be monitored closely. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).
• Hepatic effects: Use with caution in patients with hepatic disease. Transaminase elevations have been reported with NSAID use; closely monitor patients with any abnormal LFT. Rare (sometimes fatal) severe hepatic reactions (eg, fulminant hepatitis, liver necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if signs or symptoms of hepatic disease develop or if systemic manifestations occur.
• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in elderly patients, patients with diabetes and renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE inhibitors). Monitor potassium closely.
• Intra-articular infusion–related chondrolysis: Continuous intra-articular infusion of local anesthetics after arthroscopic or other surgical procedures is not an approved use; chondrolysis (primarily shoulder joint) has occurred following infusion, with some patients requiring arthroplasty or shoulder replacement. Limit exposure to articular cartilage.
• Methemoglobinemia: Has been reported with local anesthetics; clinically significant methemoglobinemia requires immediate treatment along with discontinuation of the anesthetic and other oxidizing agents. Onset may be immediate or delayed (hours) after anesthetic exposure. Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, exposure to oxidizing agents or their metabolites, or infants <6 months of age are more susceptible and should be closely monitored for signs and symptoms of methemoglobinemia (eg, cyanosis, headache, rapid pulse, shortness of breath, light-headedness, fatigue).
• Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow, which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics and ACE inhibitors or angiotensin II receptor blockers, and elderly patients are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury. Avoid use in patients with advanced renal disease unless benefits outweigh risk of worsening renal function.
• Seizures: Convulsions due to systemic toxicity leading to cardiac arrest have also been reported, presumably following unintentional intravascular injection or administration near the head or neck.
• Skin reactions: NSAIDs may cause serious skin adverse events (sometimes fatal), including exfoliative dermatitis, fixed drug eruption (including generalized bullous fixed drug eruption), Stevens-Johnson syndrome, and toxic epidermal necrolysis; may occur without warning; discontinue use at first sign of skin rash (or any other hypersensitivity).
Disease-related concerns:
• Asthma: Use is contraindicated in patients with aspirin-sensitive asthma; severe, potentially fatal bronchospasm may occur. Use caution in patients with other forms of asthma.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease, including patients with hypotension or heart block.
• Coronary artery bypass graft surgery: Risk of MI and stroke may be increased with use within the first 10 to 14 days following coronary artery bypass graft (CABG) surgery.
• Hepatic impairment: Use with caution in patients with hepatic impairment. Patients with advanced hepatic disease are at an increased risk of GI bleeding with NSAIDs.
• Renal impairment: Use is not recommended in patients with severe renal impairment. Risk of renal toxicity increased in patients with renal impairment.
Special populations:
• CYP2C9 poor metabolizers: Poor metabolizers of CYP2C9 may require dose reduction due to meloxicam component.
• Older adult: Older adults are at greater risk for serious GI, cardiovascular, and/or renal adverse events. Use with caution; consider dose reduction.
Other warnings/precautions:
• Appropriate administration: Administer as a single dose into soft tissue or periarticular surgical site by health care provider only; not for epidural, intrathecal, intra-articular, preincisional, preprocedural locoregional, or regional nerve blocks. Avoid intravascular administration; cardiac arrest and seizures have occurred following accidental intravascular injection of bupivacaine and other amide-containing products.
• Appropriate use: Safety and effectiveness of local anesthetics is dependent on proper dosage, correct technique, adequate precautions, and readiness for emergency situations. Avoid additional local anesthetic administration within 96 hours of administration of bupivacaine; monitor for cardiovascular, neurologic, and respiratory effects if additional local anesthetic administration cannot be avoided. Reduced fever and inflammation activity due to meloxicam may limit ability to detect infection. Safety and effectiveness of intra-articular use in orthopedic procedures other than for foot or ankle procedures have not been established; cartilage necrosis and degeneration have been reported in animal studies.
• Trained personnel: Clinicians using local anesthetic agents should be well trained in diagnosis and management of emergencies that may arise from the use of these agents. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Zynrelef: Bupivacaine 200 mg and meloxicam 6 mg per 7 mL (7 mL); Bupivacaine 400 mg and meloxicam 12 mg per 14 mL (14 mL)
No
Solution (Zynrelef Injection)
200-6 mg/7 mL (per mL): $26.25
400-12 mg/14 mL (per mL): $25.91
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Orthopedic or soft tissue instillation: For periarticular or soft tissue instillation into surgical site (after placement of implant[s] if applicable) by health care provider only; not for epidural, intrathecal, intra-articular, intravascular, preincisional, or preprocedural locoregional administration or for regional nerve blocks. Prepare and administer with components provided in the kit; see provided instructions with kit for detailed administration information. If a topical antiseptic has been used (eg, povidone iodine), allow site to dry prior to administration. Apply amount needed to coat the tissues without a needle into the surgical site to the tissue layers below the skin incision (do not apply directly onto subdermal layer or skin) after final irrigation and suctioning and prior to suturing of each layer; liquid will become viscous and stay in place when it comes in contact with moisture in the tissue; ensure excess product is not expressed from the site during closure. Will not degrade sutures. Minimize administration near the incision line and wipe excess from skin prior to suturing. Contact of bupivacaine/meloxicam with monofilament sutures may cause knots to loosen or untie; ≥3 knots are recommended with monofilament sutures. Braided or barbed sutures are recommended, especially for closure of deeper layers.
Orthopedic procedures: In general, apply into the wound and on the periosteum from the proximal to the distal ends of the wound (eg, beyond the boney repair).
Spinal procedures: Apply after closure of the paraspinal musculature and again after closure of the subcutaneous fascia; do not apply to the dura or spinal cord.
Total joint arthroplasty: Apply directly into the joint capsule, onto the anterior, medial, and lateral tissues (if applicable), and periosteum after placement of the components.
Soft tissue procedures: Apply into the wound prior to closure of each layer within the surgical space.
Abdominal procedures: Apply after closure of the peritoneum (if applicable) and avoid administration below the peritoneum.
Analgesia, postsurgical: For soft tissue or orthopedic surgical procedures to produce postsurgical analgesia in adults for up to 72 hours after foot and ankle procedures and other orthopedic surgical procedures (eg, 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 level spinal, and head and neck procedures.
Beers Criteria: Meloxicam is identified in the Beers Criteria as a potentially inappropriate medication to be avoided for chronic use in patients ≥65 years of age (unless alternative agents ineffective and patient can receive concomitant gastroprotective agent) due to increased risk of GI bleeding and peptic ulcer disease in older adults in high-risk category (eg, >75 years of age or receiving concomitant oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents). In addition, avoid for short-term scheduled use in combination with oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents unless alternatives are ineffective and patient can receive concomitant gastroprotective agent (Beers Criteria [AGS 2023]).
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of 5-Aminosalicylic Acid Derivatives. Risk C: Monitor
Abciximab: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Abrocitinib: Agents with Antiplatelet Effects may increase antiplatelet effects of Abrocitinib. Risk X: Avoid
Acalabrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Acemetacin: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Alcohol (Ethyl): May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. Risk C: Monitor
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Aliskiren: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Aliskiren. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor
Aminolevulinic Acid (Systemic): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid
Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor
Amiodarone: May increase serum concentration of Meloxicam. Risk C: Monitor
Amisulpride (Oral): May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Anagrelide: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Angiotensin II Receptor Blockers: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Angiotensin II Receptor Blockers may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Risk C: Monitor
Angiotensin-Converting Enzyme Inhibitors: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Risk C: Monitor
Anticoagulants (Miscellaneous Agents): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Anticoagulants (Miscellaneous Agents). Risk C: Monitor
Antiplatelet Agents (P2Y12 Inhibitors): Agents with Antiplatelet Effects may increase antiplatelet effects of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Articaine: May increase adverse/toxic effects of Local Anesthetics. Risk C: Monitor
Aspirin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may decrease therapeutic effects of Aspirin. Aspirin may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Specifically, the risk for bleeding may be increased. Aspirin may decrease serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: In general, avoid regular, frequent use of NSAIDs with aspirin whenever possible. If combined, monitor for increased bleeding and a reduced cardioprotective effect of aspirin. Risk D: Consider Therapy Modification
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bemiparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Bemiparin. Management: Avoid this combination if possible, due to an increased risk of bleeding. If coadministration cannot be avoided, monitor patients closely for clinical and laboratory evidence of bleeding. Risk D: Consider Therapy Modification
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Beta-Blockers. Risk C: Monitor
Bile Acid Sequestrants: May decrease absorption of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor
Blood Pressure Lowering Agents: May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Bradycardia-Causing Agents: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
BUPivacaine (Liposomal): BUPivacaine may increase adverse/toxic effects of BUPivacaine (Liposomal). Management: Bupivacaine may be administered immediately before, or administered in the same admixture syringe as liposomal bupivacaine as long as the ratio of the milligram dose of bupivacaine to liposomal bupivacaine does not exceed 1:2. Risk D: Consider Therapy Modification
Calcium Polystyrene Sulfonate: Meloxicam may increase adverse/toxic effects of Calcium Polystyrene Sulfonate. More specifically, concomitant use of meloxicam oral suspension (which contains sorbitol) may increase the risk for intestinal necrosis. Risk X: Avoid
Caplacizumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Caplacizumab. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Cardiac Glycosides: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Cardiac Glycosides. Risk C: Monitor
Ceritinib: Bradycardia-Causing Agents may increase bradycardic effects of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider Therapy Modification
Collagenase (Systemic): Agents with Antiplatelet Effects may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor
Corticosteroids (Systemic): May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor
CycloPHOSphamide: May increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor
CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase serum concentration of Nonsteroidal Anti-Inflammatory Agents. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs. Risk D: Consider Therapy Modification
CYP2C9 Inhibitors (Moderate): May increase serum concentration of Meloxicam. Risk C: Monitor
Dasatinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Deferasirox: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor
Deoxycholic Acid: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Desirudin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Desirudin. Risk C: Monitor
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Direct Oral Anticoagulants (DOACs): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Drospirenone-Containing Products: May increase hyperkalemic effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Enoxaparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Enoxaparin. Management: Discontinue nonselective NSAIDs prior to initiation of enoxaparin whenever possible. If coadministration cannot be avoided, monitor patients closely for clinical and laboratory evidence of bleeding. Risk D: Consider Therapy Modification
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may increase hyperkalemic effects of Eplerenone. Risk C: Monitor
Etrasimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Fexinidazole: Bradycardia-Causing Agents may increase arrhythmogenic effects of Fexinidazole. Risk X: Avoid
Fingolimod: Bradycardia-Causing Agents may increase bradycardic effects of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider Therapy Modification
Fondaparinux: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Fondaparinux. Management: Discontinue nonselective nonsteroidal anti-inflammatory agents prior to the initiation of fondaparinux, if possible. If coadministration is required, monitor patients closely for signs and symptoms of bleeding. Risk D: Consider Therapy Modification
Glycoprotein IIb/IIIa Inhibitors: Agents with Antiplatelet Effects may increase antiplatelet effects of Glycoprotein IIb/IIIa Inhibitors. Risk C: Monitor
Heparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Heparin. Risk C: Monitor
Heparins (Low Molecular Weight): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Hyaluronidase: May increase adverse/toxic effects of Local Anesthetics. Risk C: Monitor
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of HydrALAZINE. Risk C: Monitor
Hydroxyurea: May increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Ibritumomab Tiuxetan: Agents with Antiplatelet Effects may increase antiplatelet effects of Ibritumomab Tiuxetan. Risk C: Monitor
Ibrutinib: Agents with Antiplatelet Effects may increase adverse/toxic effects of Ibrutinib. Specifically, the risk of bleeding and hemorrhage may be increased. Risk C: Monitor
Ifosfamide: May increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Inotersen: Agents with Antiplatelet Effects may increase adverse/toxic effects of Inotersen. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Itraconazole: May decrease serum concentration of Meloxicam. Risk C: Monitor
Ivabradine: Bradycardia-Causing Agents may increase bradycardic effects of Ivabradine. Risk C: Monitor
Ketorolac (Nasal): May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Ketorolac (Systemic): Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Ketorolac (Systemic). Risk X: Avoid
Lacosamide: Bradycardia-Causing Agents may increase AV-blocking effects of Lacosamide. Risk C: Monitor
Landiolol: Bradycardia-Causing Agents may increase bradycardic effects of Landiolol. Risk X: Avoid
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Limaprost: May increase adverse/toxic effects of Agents with Antiplatelet Effects. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Lithium. Management: Consider reducing the lithium dose when initiating a NSAID. Monitor for increased lithium therapeutic/toxic effects if a NSAID is initiated/dose increased, or decreased effects if a NSAID is discontinued/dose decreased. Risk D: Consider Therapy Modification
Local Anesthetics: May increase adverse/toxic effects of BUPivacaine. Management: Avoid using any additional local anesthetics within 96 hours after insertion of the bupivacaine implant (Xaracoll) or bupivacaine and meloxicam periarticular solution (Zynrelef) or within 168 hours after subacromial infiltration (Posimir brand). Risk C: Monitor
Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may decrease diuretic effects of Loop Diuretics. Loop Diuretics may increase nephrotoxic effects of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Risk D: Consider Therapy Modification
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Lumacaftor and Ivacaftor: May decrease serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor
Macimorelin: Coadministration of Nonsteroidal Anti-Inflammatory Agents and Macimorelin may alter diagnostic results. Risk X: Avoid
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
MetFORMIN: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of MetFORMIN. Risk C: Monitor
Methemoglobinemia Associated Agents: May increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Methotrexate. Management: Avoid coadministration of higher dose methotrexate (such as that used for the treatment of oncologic conditions) and NSAIDs. Use caution if coadministering lower dose methotrexate and NSAIDs. Risk D: Consider Therapy Modification
Methoxsalen (Systemic): Photosensitizing Agents may increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor
Methoxyflurane: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Methoxyflurane. Risk X: Avoid
Midodrine: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Mifamurtide: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Mifamurtide. Risk X: Avoid
Miscellaneous Antiplatelets: Agents with Antiplatelet Effects may increase antiplatelet effects of Miscellaneous Antiplatelets. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nadroparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Nadroparin. Management: Coadministration of NSAIDs and nadroparin is not recommended due to an increased risk of bleeding. If coadministration is required, monitor patients closely for clinical and laboratory signs of bleeding. Risk D: Consider Therapy Modification
Naftazone: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Neuromuscular-Blocking Agents: Local Anesthetics may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents. Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Nitrous Oxide: May increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): Nonsteroidal Anti-Inflammatory Agents (Topical) may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of systemic nonsteroidal anti-inflammatory drugs (NSAIDs) and topical NSAIDs is not recommended. If systemic NSAIDs and topical NSAIDs, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider Therapy Modification
Nonsteroidal Anti-Inflammatory Agents: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk for gastrointestinal toxicity is increased. Risk X: Avoid
Obinutuzumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of bleeding may be increased. Management: Consider avoiding coadministration of obinutuzumab and agents with antiplatelet effects, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification
Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Risk C: Monitor
Ozanimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Pentosan Polysulfate Sodium: Agents with Antiplatelet Effects may increase adverse/toxic effects of Pentosan Polysulfate Sodium. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Phenylbutazone: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Pirtobrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor
Ponesimod: Bradycardia-Causing Agents may increase bradycardic effects of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider Therapy Modification
Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid
Potassium Salts: Nonsteroidal Anti-Inflammatory Agents may increase hyperkalemic effects of Potassium Salts. Risk C: Monitor
Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may increase hyperkalemic effects of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Potassium-Sparing Diuretics. Risk C: Monitor
PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Avoid coadministration of pralatrexate with nonsteroidal anti-inflammatory drugs (NSAIDs). If coadministration cannot be avoided, closely monitor for increased pralatrexate serum levels or toxicity. Risk D: Consider Therapy Modification
Probenecid: May increase serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Propranolol: May increase serum concentration of BUPivacaine. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinolones: Nonsteroidal Anti-Inflammatory Agents may increase neuroexcitatory and/or seizure-potentiating effects of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Quinolones. Risk C: Monitor
ROPivacaine: May increase adverse/toxic effects of Local Anesthetics. Risk C: Monitor
Salicylates: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase adverse/toxic effects of Salicylates. An increased risk of bleeding may be associated with use of this combination. Risk X: Avoid
Selective Serotonin Reuptake Inhibitor: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider Therapy Modification
Selumetinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Serotonin/Norepinephrine Reuptake Inhibitor: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider Therapy Modification
Siponimod: Bradycardia-Causing Agents may increase bradycardic effects of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider Therapy Modification
Sodium Phosphates: May increase nephrotoxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor
Sodium Polystyrene Sulfonate: Meloxicam may increase adverse/toxic effects of Sodium Polystyrene Sulfonate. More specifically, concomitant use of meloxicam oral suspension (which contains sorbitol) may increase the risk for intestinal necrosis. Risk X: Avoid
Sulprostone: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Sulprostone. Risk X: Avoid
Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Tacrolimus (Systemic). Risk C: Monitor
Technetium Tc 99m Tilmanocept: Coadministration of Local Anesthetics and Technetium Tc 99m Tilmanocept may alter diagnostic results. Management: Avoid mixing and simultaneously co-injecting technetium Tc 99m tilmanocept with local anesthetics. This interaction does not appear to apply to other uses of these agents in combination. Risk C: Monitor
Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider Therapy Modification
Tenoxicam: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Thiazide and Thiazide-Like Diuretics: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Thiazide and Thiazide-Like Diuretics. Thiazide and Thiazide-Like Diuretics may increase nephrotoxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Thrombolytic Agents: Agents with Antiplatelet Effects may increase adverse/toxic effects of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Tipranavir: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Tolperisone: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may increase therapeutic effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Tricyclic Antidepressants: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents. Tricyclic Antidepressants may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Risk C: Monitor
Valproic Acid and Derivatives: May increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor
Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Vancomycin. Risk C: Monitor
Vanzacaftor, Tezacaftor, and Deutivacaftor: May increase serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Risk C: Monitor
Verteporfin: Photosensitizing Agents may increase photosensitizing effects of Verteporfin. Risk C: Monitor
Vitamin E (Systemic): May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vitamin K Antagonists: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Vitamin K Antagonists. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor coagulation status closely and advise patients to promptly report any evidence of bleeding or bruising. Risk D: Consider Therapy Modification
Volanesorsen: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Zanubrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Bupivacaine crosses the placenta.
Use of meloxicam should be avoided beginning ~20 weeks gestation due to the potential for fetal renal dysfunction leading to oligohydramnios. Use at ~30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Because meloxicam can be detected in maternal plasma for >48 hours after administration, consider ultrasound monitoring of amniotic fluid.
Refer to individual monographs for additional information.
Bupivacaine and its active metabolite are present in breast milk; excretion of meloxicam is not known.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Refer to individual monographs for additional information.
The following should be monitored as clinically indicated: Serum potassium; hemoglobin or hematocrit; hepatic function; renal function; BP, heart rate, and ECG changes (particularly in patients with impaired cardiovascular function [eg, hypotension, heart block]); signs and symptoms of nonsteroidal anti-inflammatory drug (NSAID) toxicity (in patients requiring additional NSAID therapy in the postoperative period), CNS toxicity, or methemoglobinemia.
Bupivacaine: Blocks both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction.
Meloxicam: Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties. Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels. When combined with bupivacaine, the presence of meloxicam is intended to reduce local inflammation, normalize local pH, and allow for enhanced penetration of bupivacaine into the nerve, thereby synergistically potentiating the effect of bupivacaine for 72 hours (Ottoboni 2019).
Also see individual agents.
Duration: Analgesia: Up to 72 hours.
Absorption: Variable; dependent on dose and vascularity of administration site.
Half-life elimination: Terminal: Bupivacaine: 14 to 15 hours; meloxicam: 22 to 25 hours.
Time to peak:
Single dose of bupivacaine 60 mg/meloxicam 1.8 mg for bunionectomy: Median: Bupivacaine: 3 hours (range: 1.6 to 24 hours); meloxicam: 18 hours (range 8 to 60 hours).
Single dose of bupivacaine 300 mg/meloxicam 9 mg for herniorrhaphy: Median: Bupivacaine: 18 hours (range: 3 to 30 hours); meloxicam: 54 hours (range 24 to 96 hours).
Single dose of bupivacaine 400 mg/meloxicam 12 mg for knee arthroplasty: Median: Bupivacaine: 21 hours (range: 4 to 59 hours); meloxicam: 36 hours (range: 12 to 72 hours).
