Meloxicam

Pharmacologic Category

Analgesic, Nonopioid; Nonsteroidal Anti-inflammatory Drug (NSAID), Oral

Dosing: Adult

Note: Capsules and orally disintegrating tablets (ODT) are not interchangeable with other formulations of oral meloxicam even if the total milligram strength is the same. Do not substitute similar dose strengths of other meloxicam products.

Gout, acute flares (alternative agent) (off-label use): Oral: 15 mg once daily (Cheng 2004); initiate within 24 to 48 hours of flare onset preferably; discontinue 2 to 3 days after resolution of clinical signs; usual duration: 5 to 7 days (ACR [Khanna 2012]; Becker 2018)

Osteoarthritis: Capsule: Oral: Initial: 5 mg once daily; some patients may receive additional benefit from increasing dose to 10 mg once daily; maximum dose: 10 mg/day

Osteoarthritis, rheumatoid arthritis: ODT/Tablet/Suspension: Oral: Initial: 7.5 mg once daily; some patients may receive additional benefit from increasing dose to 15 mg once daily; maximum dose: 15 mg/day

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing. Use with caution; initiate dose at lower end of the dosing range.

Dosing: Renal Impairment: Adult

CrCl ≥20 mL/minute: No dosage adjustment necessary.

CrCl <20 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use is not recommended.

Hemodialysis (not dialyzable): Use with caution and monitor closely. Maximum dose: 7.5 mg/day (ODT/tablet/suspension); 5 mg/day (capsule). Note: Additional dose not necessary after hemodialysis.

KDIGO 2012 guidelines provide the following recommendations for NSAIDs:

eGFR 30 to <60 mL/minute/1.73 m²: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.

eGFR <30 mL/minute/1.73 m²: Avoid use.

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.

Dosing: Pediatric

Note: Orally-disintegrating tablets (Qmiiz ODT) and capsules are not interchangeable with other formulations of oral meloxicam even if the total milligram strength is the same; do not substitute similar dose strengths of other meloxicam products.

Juvenile idiopathic arthritis (JIA): Note: To reduce the risk of adverse cardiovascular and GI effects, use the lowest effective dose for the shortest period of time; adjust dose to specific patient's clinical needs; higher doses (up to 0.375 mg/kg/day or 15 mg/day) have not demonstrated additional benefit in clinical trials (American Pain Society 2016). Oral:

Oral suspension, tablets (limited data available with tablets): Children ≥2 years and Adolescents: 0.125 mg/kg once daily; maximum daily dose: 7.5 mg/day.

Orally-disintegrating tablets (Qmiiz ODT): Children and Adolescents weighing ≥60 kg: 7.5 mg once daily.

Dosing: Renal Impairment: Pediatric

Manufacturer's labeling:

Oral suspension: Children ≥2 years and Adolescents:

Mild to moderate impairment: No dosage adjustments are recommended.

Severe impairment (CrCl <20 mL/minute): Use is not recommended (has not been studied).

Hemodialysis: Not dialyzable; additional doses are not required after dialysis.

Orally-disintegrating tablet (Qmiiz ODT): Children and Adolescents weighing ≥60 kg:

Severe renal impairment: Use is not recommended.

Hemodialysis: In adults, lower daily doses are recommended (7.5 mg/day); however, in pediatric patients this is not possible due to available dosage forms and already reduced dose; consider alternate dosage forms.

KDIGO 2012 guidelines provide the following recommendations for NSAIDs (KDIGO 2013):

eGFR 30 to <60 mL/minute/1.73 m²: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.

eGFR <30 mL/minute/1.73 m²: Avoid use.

Dosing: Hepatic Impairment: Pediatric

Children ≥2 years and Adolescents:

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustments are recommended.

Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution; meloxicam is significantly metabolized in the liver.

Calculations

• Creatinine Clearance by Cockcroft-Gault
• Creatinine Clearance by Cockcroft-Gault (SI units)
• Creatinine Clearance by Cockcroft-Gault with IBW
• Creatinine Clearance by Cockcroft-Gault with IBW (SI units)
• Creatinine Clearance by Jelliffe
• Creatinine Clearance by Sanaka
• Glomerular Filtration Rate by Abbreviated MDRD
• Glomerular Filtration Rate by Abbreviated MDRD (SI units)
• Glomerular Filtration Rate by MDRD
• Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)
• Glomerular Filtration Rate by MDRD (SI units)
• Glomerular Filtration Rate by Schwartz
• Glomerular Filtration Rate Estimate in African Americans by AASK Equation

Use: Labeled Indications

Osteoarthritis: Relief of the signs and symptoms of osteoarthritis (OA); management of OA pain.

Rheumatoid arthritis (orally disintegrating tablet [ODT], tablet, and suspension only): Relief of signs and symptoms of rheumatoid arthritis (RA); relief of the signs and symptoms of pauciarticular or polyarticular course juvenile RA in patients ≥2 years (suspension) and in patients weighing ≥60 kg (ODT, tablet).

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Gout, acute flaresLevel of Evidence [B, G]

Data from a single-blind, randomized, controlled trial supports the efficacy of meloxicam in the treatment of acute gout flares ^Ref. Clinical experience also suggests the utility of meloxicam as an alternative agent option for acute gout flares ^Ref.

Based on the 2012 American College of Rheumatology guidelines for management of gout, NSAIDS are effective and recommended agents in the treatment of acute gout flares.

Class and Related Monographs

Nonsteroidal Anti-Inflammatory Agents

Clinical Practice Guidelines

Ankylosing Spondylitis:

ACR/SAA/SPARTAN, "2019 Update of the Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis," August 2019

Drug-Induced Liver Injury:

American College of Gastroenterology (ACG), “2014 ACG Guideline for Idiosyncratic Drug-induced Liver Injury,” July 2014

Juvenile Idiopathic Arthritis:

American College of Rheumatology, “2013 Update of the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis,” 2013

Osteoarthritis:

American College of Rheumatology, “Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee,” 2012

Surgery:

STS, “2012 Update to the Society of Thoracic Surgeons Guideline on Use of Antiplatelet Drugs in Patients Having Cardiac and Noncardiac Operations,” November 2012

Other:

“The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines,” 2011

Administration: Oral

Administer with or without meals; administer with food or milk to minimize GI irritation.

Orally disintegrating tablet (ODT): Do not remove from blister until ready to administer. Using dry hands, peel backing off the blister; do not push tablet through foil. Remove tablet and immediately place in mouth or on tongue and allow to disintegrate. Swallow with saliva (with or without drinking liquid).

Suspension: Shake oral suspension gently prior to use.

Administration: Pediatric

Oral: May be taken with or without meals; administer with food or milk to minimize gastrointestinal irritation.

Orally-disintegrating tablet (Qmiiz ODT): Children and Adolescents weighing ≥60 kg: Do not remove from blister until ready to administer. Using dry hands, peel backing off the blister; do not push tablet through foil. Remove tablet and immediately place in mouth or on tongue and allow to disintegrate. Swallow with saliva (with or without drinking liquid).

Oral suspension: Children ≥2 years and Adolescents: Shake gently prior to use.

Dietary Considerations

May be taken with food or milk to minimize gastrointestinal irritation.

Storage/Stability

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect tablets and capsules from moisture. Protect orally disintegrating tablets from exposure to excessive heat (40°C [104°F]) and humidity.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat arthritis. It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Heartburn

• Nausea

• Vomiting

• Abdominal pain

• Common cold symptoms

• Diarrhea

• Constipation

• Lack of appetite

• Passing gas

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Abdominal ulcers like severe abdominal or back pain; black, tarry, or bloody stools; vomiting blood or vomit that looks like coffee grounds; or weight gain or abnormal swelling

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding

• Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes

• Liver problems like dark urine, fatigue, lack of appetite, nausea, severe abdominal pain, light-colored stools, vomiting, or yellow skin.

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• High potassium like abnormal heartbeat, confusion, dizziness, passing out, weak, shortness of breath, numbness or tingling feeling

• Shortness of breath

• Excessive weight gain

• Swelling of arms or legs

• Chest pain

• Severe headache

• Dizziness

• Passing out

• Vision changes

• Severe loss of strength and energy

• Flu-like signs

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Geriatric Patients: High-Risk Medication:

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

NSAIDs: https://www.fda.gov/media/72932/download

Qmiiz ODT: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211210s000lbl.pdf#page=35

Contraindications

Hypersensitivity to meloxicam or any component of the formulation; history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; use in the setting of coronary artery bypass graft (CABG) surgery; phenylketonuria (ODT only).

Canadian labeling: Additional contraindications (not in US labeling): Pregnancy (third trimester); breastfeeding; severe uncontrolled heart failure; active or recent GI/gastric/duodenal/peptic ulceration/perforation; active GI bleeding; cerebrovascular bleeding or other bleeding disorders; inflammatory bowel disease (Crohn disease or ulcerative colitis); severe liver impairment or active liver disease; severe renal impairment (creatinine clearance [CrCl] <30 mL/minute or 0.5 mL/second) or deteriorating renal disease; known hyperkalemia; pediatric patients <18 years; rare hereditary conditions that may be incompatible with an excipient of the product.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.

• Cardiovascular events: [US Boxed Warning]: NSAIDs cause an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including MI and stroke. Risk may occur early during treatment and may increase with duration of use. 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 ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; 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 (ACCF/AHA [Yancy 2013]). Avoid use in patients with recent MI unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.

• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• GI events: [US Boxed Warning]: NSAIDs cause an increased risk of serious GI inflammation, ulceration, bleeding, and perforation (may be fatal); elderly patients and patients with history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. These events may occur at any time during therapy and without warning. 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), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. 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 (Bhatt 2008).

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

• Hepatic effects: Transaminase elevations have been reported with 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 the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, angiotensin-converting enzyme [ACE] inhibitors). Monitor potassium closely.

• Ophthalmic effects: Blurred and/or diminished vision has been reported; discontinue use and refer for ophthalmologic evaluation if such symptoms occur.

• 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 ARBs, and the elderly 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.

• Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning; discontinue use at first appearance of skin rash (or any other sign of hypersensitivity).

Disease-related concerns:

• Asthma: Contraindicated in patients with aspirin-sensitive asthma; severe potentially fatal bronchospasm may occur. Use caution in patients with other forms of asthma.

• Bariatric surgery: Gastric ulceration: Avoid chronic use of oral nonselective NSAIDs after bariatric surgery; development of anastomotic ulcerations/perforations may occur (Bhangu 2014; Mechanick 2013). Short-term use of celecoxib or IV ketorolac are recommended as part of a multimodal pain management strategy for postoperative pain (Chou 2016; Horsley 2019; Thorell 2016).

• Coronary artery bypass graft surgery: [US Boxed Warning]: Use is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Risk of MI and stroke may be increased with use within the first 10 to 14 days following CABG surgery.

• Hepatic impairment: Use with caution in patients with hepatic impairment; patients with hepatic impairment may require reduced doses due to extensive hepatic metabolism. Patients with advanced hepatic disease are at an increased risk of GI bleeding with NSAIDs.

• Renal impairment: Avoid use in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function; monitor closely if therapy must be initiated.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Elderly patients are at greater risk for serious GI, cardiovascular, and/or renal adverse events. Use with caution; initiate dose at the lower end of the dosing range.

• CYP2C9 poor metabolizers: Poor metabolizers of CYP2C9 may require dose reduction.

Dosage form specific issues:

• Phenylalanine: Orally disintegrating tablet (ODT): May contain phenylalanine; use is contraindicated in patients with phenylketonuria.

• Sorbitol: Oral suspension formulation may contain sorbitol. Concomitant use of sorbitol-containing products and sodium polystyrene sulfonate (Kayexalate) may cause intestinal necrosis (including fatal cases); combined use should be avoided.

Other warnings/precautions:

• Surgical/dental procedures: Withhold for at least 4 to 6 half-lives prior to surgical or dental procedures.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Men ≥65 years of age exhibited steady-state plasma concentrations and pharmacokinetics similar to younger men. Elderly women (≥65 years of age) had nearly a 50% greater AUC and 32% higher C_max compared to younger women.

Elderly patients are at high risk for adverse effects from NSAIDs. Up to 60% of elderly patients can develop an asymptomatic peptic ulcer and/or hemorrhage. Using the lowest effective dose for the shortest period possible is recommended. Use of NSAIDs can compromise existing renal function, especially when CrCl is <30 mL/minute. CNS adverse effects such as confusion, agitation, and hallucination may occur even with lower doses in elderly patients.

Warnings: Additional Pediatric Considerations

Pediatric patients ≥2 years may experience a higher frequency of some adverse effects than adults, including the following: Abdominal pain, diarrhea, fever, headache, and vomiting.

Pregnancy Considerations

Birth defects have been observed following in utero NSAID exposure in some studies; however, data is conflicting (Bloor 2013). Nonteratogenic effects, including prenatal constriction of the ductus arteriosus, persistent pulmonary hypertension of the newborn, oligohydramnios, necrotizing enterocolitis, renal dysfunction or failure, and intracranial hemorrhage have been observed in the fetus/neonate following in utero NSAID exposure. In addition, non-closure of the ductus arteriosus postnatally may occur and be resistant to medical management (Bermas 2014; Bloor 2013). Because NSAIDs may cause premature closure of the ductus arteriosus, product labeling for meloxicam specifically states use should be avoided starting at 30-weeks gestation.

Use of NSAIDs can be considered for the treatment of mild rheumatoid arthritis flares in pregnant women; however, use should be minimized or avoided early and late in pregnancy (Bermas 2014; Saavedra Salinas 2015).

The chronic use of NSAIDs in women of reproductive age may be associated with infertility that is reversible upon discontinuation of the medication. Consider discontinuing use in women having difficulty conceiving or those undergoing investigation of fertility. The use of NSAIDs close to conception may be associated with an increased risk of miscarriage (Bermas 2014; Bloor 2013).

Breast-Feeding Considerations

It is not known if meloxicam is present in breast milk.

In general, NSAIDs may be used in postpartum women who wish to breastfeed; however, agents other than meloxicam are preferred (Montgomery 2012) and use should be avoided in women breastfeeding infants with platelet dysfunction or thrombocytopenia (Bloor 2013; Sammaritano 2014). According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Lexicomp Pregnancy & Lactation, In-Depth

• Meloxicam

Briggs' Drugs in Pregnancy & Lactation

• Meloxicam

Adverse Reactions

1% to 10%:

Cardiovascular: Edema (≤5%), angina pectoris (<2%), cardiac arrhythmia (<2%), cardiac failure (<2%), facial edema (<2%), hypertension (<2%), hypotension (<2%), acute myocardial infarction (<2%), palpitations (<2%), syncope (<2%), tachycardia (<2%), vasculitis (<2%)

Central nervous system: Pain (≤5%), headache (2% to 4%), dizziness (4%), insomnia (≤4%), falling (1% to 3%), abnormal dreams (<2%), anxiety (<2%), confusion (<2%), depression (<2%), drowsiness (<2%), fatigue (<2%), malaise (<2%), nervousness (<2%), paresthesia (<2%), seizure (<2%), vertigo (<2%)

Dermatologic: Skin rash (≤3%), pruritus (≤2%), alopecia (<2%), bullous rash (<2%), diaphoresis (<2%), skin photosensitivity (<2%), urticaria (<2%)

Endocrine & metabolic: Albuminuria (<2%), dehydration (<2%), hot flash (<2%), increased gamma-glutamyl transferase (<2%), weight gain (<2%), weight loss (<2%)

Gastrointestinal: Dyspepsia (4% to 10%), diarrhea (2% to 8%), nausea (2% to 7%), abdominal pain (2% to 5%), constipation (≤3%), flatulence (≤3%), vomiting (≤3%), abdominal distress (2%), aphthous stomatitis (<2%), colitis (<2%), duodenal ulcer (<2%), dysgeusia (<2%), eructation (<2%), esophagitis (<2%), gastrointestinal perforation (1% to 4%; including duodenal, gastric), gastric ulcer (<2%), gastritis (<2%), gastroesophageal reflux disease (<2%), gastrointestinal hemorrhage (<2%), hematemesis (<2%), increased appetite (<2%), intestinal perforation (<2%), melena (<2%), pancreatitis (<2%), xerostomia (<2%)

Genitourinary: Urinary tract infection (≤7%), urinary frequency (≤2%), hematuria (<2%)

Hematologic & oncologic: Anemia (≤4%), leukopenia (<2%), nonthrombocytopenic purpura (<2%), thrombocytopenia (<2%)

Hepatic: Hepatitis (<2%), hyperbilirubinemia (<2%), increased serum alanine aminotransferase (<2%), increased serum aspartate aminotransferase (<2%)

Hypersensitivity: Angioedema (<2%), hypersensitivity reaction (<2%)

Neuromuscular & skeletal: Arthralgia (≤5%), back pain (≤3%), tremor (<2%)

Ophthalmic: Conjunctivitis (<2%), visual disturbance (<2%)

Otic: Tinnitus (<2%)

Renal: Increased blood urea nitrogen (<2%), increased serum creatinine (<2%), renal failure syndrome (<2%)

Respiratory: Upper respiratory tract infection (≤8%), flu-like symptoms (3% to 6%), pharyngitis (3%), bronchospasm (2%), dyspnea (2%), cough (≤2%), asthma (<2%)

Miscellaneous: Accidental injury (≤5%), fever (<2%)

<1%, postmarketing, and/or case reports: Acute urinary retention, agranulocytosis, anaphylaxis, erythema multiforme, exfoliative dermatitis, hepatic failure, hepatotoxicity (idiosyncratic) (Chalasani 2014), interstitial nephritis, jaundice, mood changes, nonimmune anaphylaxis, renal insufficiency, renal papillary necrosis, shock, Stevens-Johnson syndrome, toxic epidermal necrolysis

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Nonsteroidal Anti-inflammatory Drug (NSAID) Allergy

Toxicology

• Nonsteroidal Anti-inflammatory Drugs

Metabolism/Transport Effects

Substrate of CYP2C9 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

5-Aminosalicylic Acid Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives. Risk C: Monitor therapy

Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Acemetacin: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. Risk C: Monitor therapy

Aliskiren: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction. Risk C: Monitor therapy

Alpelisib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy

Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin. Risk C: Monitor therapy

Apixaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Bemiparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin and nonsteroidal anti-inflammatory agents (NSAIDs) due to the increased risk of bleeding. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk D: Consider therapy modification

Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor therapy

Calcium Polystyrene Sulfonate: Meloxicam may enhance the adverse/toxic effect 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 combination

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the 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 Inducers (Moderate): May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Meloxicam. Risk C: Monitor therapy

Dabigatran Etexilate: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Deferasirox: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy

Dexibuprofen: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Dexibuprofen. Risk X: Avoid combination

Dexketoprofen: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Diclofenac (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Seek alternatives to the combined use of diclofenac with other nonsteroidal anti-inflammatory agents (NSAIDs). Avoid the use of diclofenac/misoprostol with other NSAIDs. Risk D: Consider therapy modification

Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Drospirenone: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Drospirenone. Risk C: Monitor therapy

Edoxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Enoxaparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue nonsteroidal anti-inflammatory agents (NSAIDs) prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy

Fat Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Felbinac: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Floctafenine: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Haloperidol: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion. Risk C: Monitor therapy

Heparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or nonsteroidal anti-inflammatory agents (NSAIDs) if coadministration is required. Risk D: Consider therapy modification

Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures. Risk D: Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Management: Concomitant treatment with these agents should generally be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed. Risk D: Consider therapy modification

HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Itraconazole: May decrease the serum concentration of Meloxicam. Risk C: Monitor therapy

Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Ketorolac (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Risk D: Consider therapy modification

Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect 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

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy

Macimorelin: Nonsteroidal Anti-Inflammatory Agents may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination

MetFORMIN: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of MetFORMIN. Risk C: Monitor therapy

Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Alternative anti-inflammatory therapy should be considered whenever possible, especially if the patient is receiving higher, antineoplastic doses of methotrexate. Risk D: Consider therapy modification

Mifamurtide: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide. Risk X: Avoid combination

MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Risk D: Consider therapy modification

Morniflumate: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Naftazone: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Risk X: Avoid combination

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of nonsteroidal antiinflammatory drugs (NSAIDs) with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid combination

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Pelubiprofen: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Phenylbutazone: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. Risk C: Monitor therapy

Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Risk C: Monitor therapy

Quinolones: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. Risk C: Monitor therapy

Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy

Rivaroxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Salicylates: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Exceptions: Choline Magnesium Trisalicylate. Risk D: Consider therapy modification

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. 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

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect 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

Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification

Sodium Polystyrene Sulfonate: Meloxicam may enhance the adverse/toxic effect 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 combination

Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Talniflumate: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect 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. Risk D: Consider therapy modification

Tenoxicam: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Tolperisone: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may enhance the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Tricyclic Antidepressants (Tertiary Amine): May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination

Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the anticoagulant effect 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

Voriconazole: May increase the serum concentration of Meloxicam. Risk C: Monitor therapy

Zaltoprofen: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Test Interactions

May lead to false-positive aldosterone/renin ratio (ARR) (Funder 2016)

Genes of Interest

• CYP2C9 - Meloxicam
• HLA-B Major Histocompatability Complex
• Leukotriene C4 Synthase

Monitoring Parameters

Complete blood cell count (CBC) and chemistry profile; occult blood loss, and periodic liver function tests; renal function (urine output, serum BUN and creatinine); signs or symptoms of GI bleeding; blood pressure; periodic ophthalmologic exam with long term therapy.

Advanced Practitioners Physical Assessment/Monitoring

Evaluate cardiac risk and potential for GI bleeding prior to prescribing this medication. Monitor blood pressure at the beginning of therapy and periodically during use.

Nursing Physical Assessment/Monitoring

Monitor blood pressure at the beginning of therapy and periodically during use. Monitor for gastrointestinal effects and ototoxicity at beginning of therapy and periodically throughout.

Product Availability

Anjeso 30 mg/mL injection: FDA approved February 2020; availability anticipated in the 2^nd quarter of 2020. Anjeso is indicated for use in adults for the management of moderate-to-severe pain, alone or in combination with non-NSAID analgesics. Information pertaining to this product within the monograph is pending revision. Consult the prescribing information for additional information.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Vivlodex: 5 mg [contains fd&c blue #2 (indigotine), fd&c red #40, fd&c yellow #6 (sunset yellow)]

Vivlodex: 10 mg [contains carmine, fd&c blue #2 (indigotine), fd&c red #40, fd&c yellow #6 (sunset yellow)]

Vivlodex: 10 mg [DSC] [contains fd&c blue #2 (indigotine), fd&c red #40, fd&c yellow #6 (sunset yellow)]

Injectable, Intravenous [preservative free]:

Anjeso: 30 mg/mL (1 mL)

Suspension, Oral:

Mobic: 7.5 mg/5 mL (100 mL [DSC]) [contains saccharin sodium, sodium benzoate]

Tablet, Oral:

Mobic: 7.5 mg, 15 mg

Generic: 7.5 mg, 15 mg, 15 mg

Tablet Disintegrating, Oral:

Qmiiz ODT: 7.5 mg, 15 mg [contains aspartame]

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Mobicox: 7.5 mg [DSC], 15 mg [DSC]

Generic: 7.5 mg, 15 mg

Anatomic Therapeutic Chemical (ATC) Classification

• M01AC06

Generic Available (US)

May be product dependent

Pricing: US

Capsules (Vivlodex Oral)

5 mg (per each): $34.50

10 mg (per each): $34.50

Tablet, orally-disintegrating (Qmiiz ODT Oral)

7.5 mg (per each): $8.10

15 mg (per each): $8.10

Tablets (Meloxicam Oral)

7.5 mg (per each): $0.17 - $3.17

15 mg (per each): $4.26 - $4.85

Tablets (Mobic Oral)

7.5 mg (per each): $10.73

15 mg (per each): $16.41

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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.

Pharmacodynamics/Kinetics

Distribution:

Children 2 to 6 years (n=7): Apparent V_d: 0.19 L/kg (Burgos-Vargas 2004)

Children and Adolescents 7 to 16 years (n=11): Apparent V_d: 0.13 L/kg (Burgos-Vargas 2004)

Adults: Vd_ss~10 L

Protein binding: ~99%, primarily to albumin; Note: Free fraction was higher in adult patients with renal failure who were receiving chronic dialysis.

Metabolism: Hepatic via CYP2C9 and CYP3A4 (minor); forms 4 metabolites (inactive)

Bioavailability: 89% (capsule); suspension is bioequivalent to tablets

Half-life elimination:

Children 2 to 6 years (n=7): 13.4 hours (Burgos-Vargas 2004)

Children and Adolescents 7 to 16 years (n=11): 12.7 hours (Burgos-Vargas 2004)

Adults: ~15 to 22 hours

Time to peak:

Children and Adolescents 2 to 16 years (n=18): Suspension: Initial: 1 to 3 hours; secondary: 6 to 12 hours (Burgos-Vargas 2004)

Adults: Initial: Within 2 hours (capsule); 4 to 5 hours (tablet); 4 to 12 hours (ODT; prolonged with food); Secondary: ~8 hours (capsule); 12 to 14 hours (tablet)

Excretion: Urine and feces (as inactive metabolites); <1% excreted unchanged in urine

Clearance:

Children 2 to 6 years (n=7): 0.17 mL/minute/kg (Burgos-Vargas 2004)

Children and Adolescents 7 to 16 years (n=11): 0.12 mL/minute/kg (Burgos-Vargas 2004)

Adults: 7 to 9 mL/minute

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Meloxicam plasma concentration is decreased and total clearance increased in patients with renal impairment.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Taste perversion, ulcerative stomatitis, and xerostomia (normal salivary flow resumes upon discontinuation). The dentist should be aware of the potential of abnormal coagulation. Caution should also be exercised in the use of NSAIDs in patients already on anticoagulant therapy with drugs such as warfarin (Coumadin®). See Effects on Bleeding.

Effects on Bleeding

Nonselective NSAIDs such as meloxicam inhibit platelet aggregation and prolong bleeding time in some patients. Unlike aspirin, the NSAID effect on platelet function is quantitatively less, of shorter duration, and reversible.

Related Information

• Beers Criteria 2019: Potentially Inappropriate Medication Use in Older Adults ≥65 Years of Age
• Nonsteroidal Anti-inflammatory Drugs

Index Terms

Anjeso

FDA Approval Date

April 14, 2000

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Brand Names: International

Acticam (CR, DO, GT, HN, NI, PA, SV); Aflamid (MX); Afloxx (PE); Areloger (IE); Aroxicam (ET); Arrox (HK, MY); Artriclox (CO); Aspicam (UA); Avegesic (MY); Bexxam (PH); Bienex (CR, DO, EC, GT, HN, NI, PA, SV); Cambic-15 (TH); Camrox (KR); Caxlem (PH); Cloxim (PH); Coxicam (EC, QA); Dormelox (BR); Ecax (CL); Ecwin (IN); Exel (MX); Flamoxi (ID); Flexicam (AE, ET); Flodin (PE); Friart (ID); Hyflex (PY); Ilacox (CR, DO, GT, HN, NI, PA, SV); Koniflam (ID); Letex (PY); Loxaid (PH); Loxibest (MX); Loxicam (JO); Loxikam (BD); Loxil (ID); M-Cam (TZ); M.P.Osoth 15 (TH); Mebilax (VN); Mecaron (KR); Mecasel (VN); Mecon (TW); Mecox (ID); Medoxicam (AE); Mel-OD (MY, TH); Melart (PH); Melcam (BD, HK, IE, TH); Melcox (KR); Melflam (HK); Meliam (HR); Melicam (TW); Melocam (AE, CO, CY, EG, IL, IQ, IR, JO, KR, KW, LY, MY, OM, SA, SY, YE); Melocid (MT); Melocox (KR, PH); Melodyn (AT); Meloflam (PH); Melonax (ET); Melone (IN); Melosteral (MX); Melox (AE, BH, CY, IL, IQ, IR, JO, KR, KW, LV, LY, MT, MY, OM, QA, RO, SA, SG, SY, TH, TW, YE); Meloxibell (AU); Meloxin (ID); Memovic (KR); Merapiran (AR); Mevamox (BR); Mexicam (EG); Mexolan (LV); Mexpharm (ID); Mexx (PH); Miloxam (AE, CY, IL, IQ, IR, JO, KW, LY, OM, SA, SY, YE); Miovalis (AU); Mobec (DE); Mobex (KR); Mobic (AE, AR, AU, BB, BE, BF, BH, BJ, BM, BS, BZ, CI, CN, CO, CY, DK, EC, EG, ET, FI, FR, GB, GH, GM, GN, GY, HK, IE, IL, IQ, IR, IT, JM, JO, KE, KR, KW, LB, LR, LU, LY, MA, ML, MR, MT, MU, MW, MY, NE, NG, NZ, OM, PE, PH, PY, QA, SA, SC, SD, SE, SG, SL, SN, SR, SY, TH, TN, TR, TT, TW, TZ, UG, UY, VE, VN, YE, ZA, ZM, ZW); Mobicox (CH, CR, CU, DO, GT, HN, MX, NI, PA, SV); Mobiflex (ID); Mobiglan (IE); Mobitil (ET); Mobix (PK); Moov (VN); Mopik (TW); Motion (LB); Movalis (BG, CZ, EE, ES, HR, IS, LT, LV, PL, PT, RO, RU, SI, SK, UA); Moven (BH, LB, QA); Movi-Cox (ID); Moxalid (GR); Moxicam (AU, KR); Muvera (IN); Muvik (IN, LK); Neoxicam (BH, PH, QA); Nulox (ID, SG); Nulox Forte (ID); Ostelox (ID, LK); Osteoflam (PH); Oxichem (LK); Oximal (LB); Parocin (ES); Paxicam (ID); Quicktra (HR); Rafree (IN, PH); Recoxa (LV); Selektine (LB, SA); Troxicam (KR); Xiarax (EC); Xobix (LK); Zeloxim (ET)

Last Updated 3/12/20