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.
Flurbiprofen is contraindicated during the perioperative setting of coronary artery bypass graft (CABG) surgery.
NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.
Note: Safety: Use the lowest effective dose for the shortest duration of time. Avoid or use with caution in patients at risk for or with existing cardiovascular disease, GI disease, kidney impairment, chronic liver disease, or a bleeding diathesis due to greater risk for adverse events. Consider administering in combination with a proton pump inhibitor in patients at risk for GI bleeding (eg, taking dual antiplatelet therapy or an anticoagulant, ≥60 years of age, high doses) (Ref).
Acute pain (off label): Oral: 150 to 300 mg/day in 3 to 4 divided doses as needed (Ref).
Ankylosing spondylitis (off label): Oral: 50 mg 2 to 4 times daily; some patients may require up to 300 mg/day during symptom exacerbations (Ref).
Dysmenorrhea (off label): Oral: 50 mg 4 times daily (Ref).
Osteoarthritis: Oral: Initial: 200 to 300 mg/day in 2 to 4 divided doses; maximum: 100 mg/dose.
Rheumatoid arthritis: Oral: Initial: 200 to 300 mg/day in 2 to 4 divided doses; maximum: 100 mg/dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Moderate to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be necessary due to possible metabolite accumulation. Avoid use in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function.
Continuous ambulatory peritoneal dialysis: Not removed by dialysis.
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.
Hepatic impairment prior to treatment initiation:
There are no dosage adjustments provided in the manufacturer's labeling; use with caution to avoid adverse effects and discontinue if hepatic function worsens.
Hepatotoxicity during treatment:
Discontinue treatment if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur.
Refer to adult dosing. Reduce the initial dose to the lower end of the dosing range. 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.
1% to 10%:
Cardiovascular: Edema (≥1%)
Dermatologic: Skin rash (≥1%)
Endocrine & metabolic: Weight changes (≥1%)
Gastrointestinal: Abdominal pain (≥1%), constipation (≥1%), diarrhea (≥1%), dyspepsia (≥1%), flatulence (≥1%), gastrointestinal hemorrhage (≥1%), heartburn (≥1%), nausea (≥1%), vomiting (≥1%)
Hepatic: Increased liver enzymes (≥1%)
Nervous system: Amnesia (≥1%), anxiety (≥1%), asthenia (≥1%), depression (≥1%), dizziness (≥1%), drowsiness (≥1%), headache (≥1%), hyperreflexia (≥1%), insomnia (≥1%), malaise (≥1%), nervousness (≥1%), tremor (≥1%)
Ophthalmic: Visual disturbance (≥1%; including blurred vision and vision loss)
Otic: Tinnitus (≥1%)
Respiratory: Rhinitis (≥1%)
<1%:
Cardiovascular: Acute myocardial infarction, heart failure, hypertension, vascular disease, vasodilation
Dermatologic: Alopecia, eczema, pruritus, urticaria, xeroderma
Endocrine & metabolic: Hyperuricemia
Gastrointestinal: Bloody diarrhea, disease of esophagus, gastrointestinal ulcer (including gastric ulcer and peptic ulcer), gastritis, glossitis, hematemesis, stomatitis, xerostomia
Genitourinary: Hematuria, vaginal hemorrhage
Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, eosinophilia, iron deficiency anemia, purpuric disease
Hepatic: Hepatitis
Hypersensitivity: Anaphylaxis, angioedema
Infection: Herpes simplex infection
Nervous system: Altered sense of smell, ataxia, cerebral ischemia, chills, confusion, emotional lability, hypertonia, paresthesia, seizure, twitching, vertigo
Ophthalmic: Conjunctivitis, corneal opacity
Renal: Renal failure syndrome
Respiratory: Asthma, bronchitis, dyspnea, epistaxis, laryngitis
Miscellaneous: Fever
Frequency not defined:
Cardiovascular: Coronary thrombosis
Gastrointestinal: Gastrointestinal inflammation, gastrointestinal perforation
Postmarketing:
Cardiovascular: Angina pectoris, cardiac arrhythmia, pulmonary embolism
Dermatologic: Diaphoresis, ecchymoses, exfoliative dermatitis, nail disease, skin photosensitivity, Stevens-Johnson syndrome (Khan 2022), toxic epidermal necrolysis
Endocrine & metabolic: Hyperkalemia, menstrual disease
Gastrointestinal: Change in appetite, cholecystitis, colitis, dysgeusia, enteritis, exacerbation of Crohn disease, exacerbation of ulcerative colitis, periodontal abscess
Genitourinary: Prostatic disease, uterine hemorrhage, vulvovaginitis
Hematologic & oncologic: Agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, lymphadenopathy, pancytopenia, thrombocytopenia
Hepatic: Hepatotoxicity (idiosyncratic) (Chalasani 2021), jaundice (including cholestatic jaundice) (Dogan 2014)
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms, type I hypersensitivity reaction (Mehra 2010), type IV hypersensitivity reaction (Romano 1997)
Infection: Herpes zoster infection
Nervous system: Cerebrovascular accident, meningitis, myasthenia, parkinsonism (Enevoldson 1990), retrobulbar neuritis, subarachnoid hemorrhage
Ophthalmic: Glaucoma, retinal hemorrhage
Otic: Ear disease, hearing loss
Renal: Interstitial nephritis (Tazoe 1987)
Respiratory: Hyperventilation, pulmonary infarct
Hypersensitivity to flurbiprofen or any component of the formulation; history of asthma, urticaria, or allergic-type reactions after taking aspirin or other nonsteroidal anti-inflammatory drugs; use in the setting of coronary artery bypass graft surgery.
Canadian labeling: Additional contraindications (not in US labeling): Active or recent history of inflammatory diseases of the GI system (peptic ulcer, gastritis, regional enteritis, or ulcerative colitis); inflammatory bowel disease; severe liver impairment or active liver disease; severe renal impairment (CrCl <30 mL/min) or deteriorating renal disease; known hyperkalemia; cerebrovascular bleeding or other bleeding disorders; severe uncontrolled heart failure; third trimester of pregnancy; breastfeeding; pediatric patients <18 years of age.
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: Relative risk of serious adverse cardiovascular thrombotic events 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 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 heart failure (FDA 2015). Avoid use in patients with a recent myocardial infarction (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).
• 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 due to increased risk of serious GI events. In patients with a history of acute lower gastrointestinal 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 the 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).
• Genitourinary effects: NSAIDs may be associated with persistent urinary symptoms (bladder pain, dysuria, urinary frequency), hematuria, or cystitis. The onset of these symptoms may occur at any time after the initiation of therapy. Some cases have become severe on continued treatment; discontinue therapy to ascertain if symptoms disappear.
• 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, 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, 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 sign of skin rash (or any other hypersensitivity).
Disease-related concerns:
• Aseptic meningitis: NSAIDs may increase the risk of aseptic meningitis (rare), especially in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders.
• 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 2020). 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: Risk of MI and stroke may be increased with use 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 and kidney failure with NSAIDs (AASLD [Biggins 2021]; AASLD [Runyon 2013]).
• Renal impairment: Use with caution; dosage adjustment in patients with moderate or severe impairment may be necessary due to possible metabolite accumulation. 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.
Special populations:
• Older adult: Older adult patients are at greater risk for serious GI, cardiovascular, and/or renal adverse events. Use with caution; consider reducing the initial dose.
Other warnings/precautions:
• Surgical/dental procedures: Withhold for at least 4 to 6 half-lives prior to surgical or dental procedures.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Lurbipr: 100 mg [contains fd&c blue #1 (brill blue) aluminum lake]
Generic: 50 mg, 100 mg
Yes
Tablets (Flurbiprofen Oral)
50 mg (per each): $0.79
100 mg (per each): $1.19 - $4.43
Tablets (Lurbipr Oral)
100 mg (per each): $3.60
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 50 mg, 100 mg
Oral: May administer with food, milk, or antacids.
An FDA-approved patient medication guide, which is available with the product information and at NSAIDs Class Medication Guide, must be dispensed with this medication.
Osteoarthritis, rheumatoid arthritis: Relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis.
Ankylosing spondylitis; Dysmenorrhea; Pain
Flurbiprofen may be confused with fenoprofen
Ansaid may be confused with Asacol, Axid
Beers Criteria: Based on pharmacologic class concerns for Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in the Beers Criteria, flurbiprofen may be a potentially inappropriate medication to be avoided in patients 65 years and older for chronic use (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, older than 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]).
Substrate of CYP2C9 (Major with inhibitors), CYP2C9 (Minor with inducers); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
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
Aliskiren: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Aliskiren. Risk C: Monitor
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
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
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
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
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
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
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
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 Flurbiprofen (Systemic). 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
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
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
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
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of HydrALAZINE. 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
Inotersen: Agents with Antiplatelet Effects may increase adverse/toxic effects of Inotersen. Specifically, the risk of bleeding may be increased. 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
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
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
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
MetFORMIN: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of MetFORMIN. 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
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
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
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
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
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
Phenylbutazone: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
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
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
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
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
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
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
Sodium Phosphates: May increase nephrotoxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor
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
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
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
Food may decrease the rate but not the extent of absorption. Management: May administer with food, milk, or antacid to decrease GI effects.
Nonsteroidal anti-inflammatory drugs (NSAIDs) may delay or prevent rupture of ovarian follicles. This may be associated with infertility that is reversible upon discontinuation of the medication. Consider discontinuing use in patients having difficulty conceiving or those undergoing investigation of fertility.
Based on available information, NSAIDs can be continued in males with rheumatic and musculoskeletal diseases who are planning to father a child (ACR [Sammaritano 2020]).
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) close to conception may be associated with an increased risk of miscarriage due to cyclooxygenase-2 inhibition interfering with implantation (Bermas 2014; Bloor 2013).
Birth defects have been observed following in utero NSAID exposure in some studies; however, data are 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 (Bermas 2014; Bloor 2013). Maternal NSAID use may cause fetal renal dysfunction leading to oligohydramnios. Although rare, this may occur as early as 20 weeks' gestation and is more likely to occur with prolonged maternal use. Oligohydramnios may be reversible following discontinuation of the NSAID (Dathe 2019; FDA 2020). In addition, nonclosure of the ductus arteriosus postnatally may occur and be resistant to medical management (Bermas 2014; Bloor 2013).
Maternal use of NSAIDs should be avoided beginning at 20 weeks' gestation. If NSAID use is necessary between 20 and 30 weeks' gestation, limit use to the lowest effective dose and shortest duration possible; consider ultrasound monitoring of amniotic fluid if treatment extends beyond 48 hours and discontinue the NSAID if oligohydramnios is found. Because NSAIDs may cause premature closure of the ductus arteriosus, prescribing information for flurbiprofen specifically states use should be avoided starting at ~30 weeks' gestation.
Based on available information, NSAIDs can be continued during the first 2 trimesters of pregnancy in patients with rheumatic and musculoskeletal diseases; use in the third trimester is not recommended (ACR [Sammaritano 2020]).
Flurbiprofen is present in breast milk (Cox 1987; Hassan 2019; Smith 1989).
• Breast milk was sampled following a single oral dose of flurbiprofen 200 mg in one lactating patient, 12 months postpartum. Two hours after the dose, the breast milk concentration was 0.16 mcg/mL (Hassan 2019). Using a milk concentration of 0.16 mcg/mL, the estimated infant dose via breast milk is 24 mcg/kg/day providing a relative infant dose (RID) of 0.84% compared to a weight-adjusted maternal dose of 200 mg/day.
• Flurbiprofen breast milk concentrations were evaluated in 10 breastfeeding patients ≥1 month postpartum. All mothers were given a single oral dose of flurbiprofen 100 mg and breast milk was sampled ≥24 hours. The maximum flurbiprofen concentration in breast milk occurred at 3 hours after the dose and was 0.09 mcg/mL, providing an estimated daily infant dose of 13.5 mcg/kg/day (RID 0.9%). Flurbiprofen was measurable in the breast milk of only 5 patients and was not measurable in any sample taken ≥24 hours after the dose (Cox 1987).
• In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).
Flurbiprofen was not found to increase the risk of hyperbilirubinemia in full-term breastfed infants. The study evaluated infant bilirubin levels obtained within 48 hours after delivery between postpartum mothers taking at least 3 doses of flurbiprofen (n=132) to those taking acetaminophen (n=348). Hyperbilirubinemia was observed in 1 infant exposed to flurbiprofen via breast milk (0.76%) compared to 7 exposed to acetaminophen (2.01%). The difference was not statistically significant (Fu 2020).
Nonopioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs), are preferred for breastfeeding patients who require pain control peripartum or for surgery outside of the postpartum period (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]). NSAIDs are considered compatible for use in patients with rheumatic and musculoskeletal diseases who are breastfeeding; agents with a short half-life and established safety data in infants may be preferred (ACR [Sammaritano 2020].
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 benefits of treatment to the mother. Maternal use of NSAIDs should be avoided if the breastfeeding infant has platelet dysfunction, thrombocytopenia, or a ductal-dependent cardiac lesion (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]; Bloor 2013).
CBC, 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.
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.
Absorption: Rapid
Distribution: Vd: 0.12 L/kg
Protein binding: >99%, primarily albumin
Metabolism: Hepatic via CYP2C9; major metabolite is 4-hydroxy-flurbiprofen (inactive)
Bioavailability: 96%
Half-life elimination: 4.7 to 5.7 hours
Time to peak: ~2 hours
Excretion: Urine (<3% as unchanged; ~70% primarily as metabolites)
Altered kidney function: Elimination of flurbiprofen metabolites may be reduced; plasma protein binding may be decreased.
Hepatic function impairment: Hepatically eliminated (>90%); protein binding may be decreased.