Version November 2024
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. This risk may occur early in the treatment and may increase with duration of use.
Celecoxib is contraindicated in the 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 higher risk for serious GI events.
Dosage guidance:
Safety: 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 celecoxib doses) (Ref).
Dosing: Use the lowest effective dose for the shortest duration of time.
Anti-inflammatory (eg, for arthritis associated with inflammatory rheumatic disease): Oral: Initial: 200 mg once daily or 100 mg twice daily; may increase to a maximum of 200 mg twice daily for several weeks during a disease flare until the flare resolves.
Dysmenorrhea: Oral: Initial: 400 mg, followed by an additional 200 mg approximately 12 hours later, if needed, on day 1; maintenance dose: 200 mg twice daily as needed; maximum daily maintenance dose: 400 mg/day. Begin at menses onset or 1 to 2 days prior to onset of menses for severe symptoms; usual duration: 1 to 5 days (Ref).
Gout, treatment, acute flares (off-label use):
Oral: Initial: 400 mg, followed by 200 mg approximately 12 hours later on day 1, then continue 200 mg twice daily thereafter; maximum daily maintenance dose: 400 mg/day (Ref). Initiate within 24 to 48 hours of flare onset; reduce dose as symptoms improve. Discontinue a few days after resolution of clinical signs (usual total duration: 5 to 7 days); longer duration may be required if therapy is delayed (Ref).
Migraine, acute treatment:
Note: Limit use to ≤14 days per month to avoid medication-overuse headache (Ref). For use as monotherapy in mild to moderate attacks not associated with vomiting or severe nausea (Ref). Administration early in the course of a migraine attack, at the first sign of pain, may improve response to treatment (Ref).
Oral: 120 mg as a single dose. Maximum: 120 mg per 24 hours (Ref).
Osteoarthritis: Oral: 200 mg/day in 1 or 2 divided doses; administer as needed or scheduled (Ref). In patients with inadequate relief using 200 mg/day, may increase up to 400 mg/day (ie, 200 mg twice daily as needed or scheduled) based on some experts (Ref). Use the lowest effective dose for the shortest amount of time.
Pain, acute (labeled use) and chronic (off-label use):
Acute pain: Oral: Initial: 400 mg, followed by 200 mg ~12 hours later, if needed, on day 1; thereafter, 200 mg twice daily as needed or scheduled; maximum: 400 mg/day.
Chronic pain not associated with osteoarthritis (eg, musculoskeletal): Oral: 200 mg once daily or 100 to 200 mg twice daily as needed or scheduled; do not exceed 400 mg/day (Ref). Use the lowest effective dose for the shortest amount of time.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
CrCl ≥60 mL/minute: No dosage adjustment necessary (<1% of the drug excreted in the urine) (Ref).
CrCl >30 to <60 mL/minute: No dosage adjustment necessary (<1% of the drug excreted in the urine) (Ref). However, use the lowest effective dose for the shortest duration possible. Use of analgesics other than nonsteroidal anti-inflammatory drugs (NSAIDs) or topical NSAIDs may be preferred. Avoid use in patients at high risk for acute kidney injury (ie, volume depleted, hypotensive, elderly, or taking concurrent nephrotoxic medications) (Ref).
CrCl ≤30 mL/minute: Avoid use due to increased risk of acute kidney injury (Ref); Use of analgesics other than NSAIDs or topical NSAIDs are preferred. However, in select patients where alternatives are not effective, after careful assessment of risks versus benefits, use of celecoxib may be considered; use the lowest effective dose for the shortest duration possible with close monitoring of kidney function (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzable (high protein binding, large Vd): Avoid use, as patients with end-stage kidney disease may be at increased risk for bleeding (eg, GI), cardiovascular adverse effects, and loss of residual kidney function (Ref). However, in select patients after careful assessment of risks versus benefits, use of celecoxib may be considered; use the lowest effective dose for the shortest duration possible (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzable (high protein binding, large Vd): Avoid use, as patients with end-stage kidney disease may be at increased risk for bleeding (eg, GI), cardiovascular adverse effects, and loss of residual kidney function (Ref). However, in select patients after careful assessment of risks versus benefits, use of celecoxib may be considered; use the lowest effective dose for the shortest duration possible (Ref).
CRRT: Avoid use (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Avoid use (Ref).
Acute kidney injury while on celecoxib therapy: Discontinue use (Ref).
Mild impairment (Child-Pugh class A): No dosage adjustment necessary; AUC increased ~40% in mild hepatic impairment compared with healthy subjects.
Moderate impairment (Child-Pugh class B): Reduce dose by 50%.
Severe impairment (Child-Pugh class C): Use is not recommended.
Abnormal liver function tests (persistent or worsening): Discontinue use.
Initiate at the lowest recommended dose. The AUC in older adults (>65 years of age, especially females and patients weighing <50 kg) may be increased by 50% compared with younger subjects.
(For additional information see "Celecoxib: Pediatric drug information")
Juvenile idiopathic arthritis (JIA): Note: Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals.
Children ≥2 years and Adolescents:
≥10 kg to ≤25 kg: Oral: 50 mg twice daily.
>25 kg: Oral: 100 mg twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥2 years and Adolescents: Oral:
Baseline:
Mild or moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, since <1% of the drug is excreted in the urine, dosage adjustment is not necessary (Ref). Based on unpublished data, AUC was ~40% lower in adult patients with chronic renal insufficiency (GFR 35 to 60 mL/minute) compared with subjects with normal renal function due to a higher apparent clearance.
Severe impairment: Use is not recommended.
Advanced renal disease: Use is not recommended; however, if celecoxib treatment cannot be avoided, monitor renal function closely.
During therapy: Abnormal renal function tests (persistent or worsening): Discontinue use.
Children ≥2 years and Adolescents: Oral:
Moderate hepatic impatient: Reduce dose by 50%; monitor closely.
Severe hepatic impairment: Use is not recommended; has not been studied.
Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of serious adverse cardiovascular (CV) events, including acute myocardial infarction (MI), cerebrovascular accident, and CV death. New-onset hypertension or exacerbation of hypertension may occur with NSAID use which may also contribute to an increased risk of CV events (Ref). New-onset or exacerbation of heart failure may also occur with cyclooxygenase (COX)-2 selective NSAIDs (ie, coxibs), including celecoxib, and nonselective NSAIDs (eg, naproxen) resulting in an increased risk of hospitalizations for heart failure and death in patients with heart failure (Ref).
Data collected by the Coxib and traditional NSAID Trialists’ (CNT) Collaborative has shown that use of COX-2 selective NSAIDs, including celecoxib, may increase the risk of major vascular events as compared to nonselective NSAIDs (Ref); however, data from the PRECISION trial showed no difference with regards to risk between celecoxib, naproxen, or ibuprofen after a treatment duration of therapy of ~3 years (Ref). Additional trials and registry data are also conflicted with regards to the comparative risk of CV events among the COX-2 selective and nonselective NSAIDs (Ref). However, data in those with established heart disease consistently reveals an increased risk of harm with NSAID use (Ref). The FDA states that there is insufficient data to determine if risk of MI or stroke is definitely higher or lower for any particular NSAID as compared to another (Ref).
Mechanism: Dose- and time-related; inhibition of COX-2 by NSAIDs results in a reduction in the production of prostaglandin I2 (prostacyclin) in the vascular endothelium (Ref); animal studies have shown that reduced prostacyclin activity may result in a predisposition to vascular injury (Ref). In addition, prostaglandins inhibit sodium resorption in the thick ascending loop of Henle and collecting tubule; therefore, a reduction in prostaglandin synthesis by NSAIDs may cause sodium and fluid retention and result in hypertension and decreased efficacy of diuretics (Ref).
Onset: Varied; increased risk may be apparent within the first weeks following initiation of treatment (Ref); longer duration of therapy may further increase risk (Ref).
Risk factors:
• ≥65 years of age
• Higher doses (especially with regards to CV thrombotic risk) (Ref)
• Longer duration of use and frequent use (eg, ≥22 days per month) (Ref)
• Preexisting cardiovascular disease (CVD) or presence of risk factors for CVD, including use following coronary artery bypass graft surgery (Ref)
- Note: Relative risk appears to be similar in those with and without known CVD or risk factors for CVD; however, absolute incidence of serious CV thrombotic events appears to be higher in patients with known CVD or risk factors for CVD due to an increased baseline risk (Ref)
Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of serious gastrointestinal (GI) adverse events, including gastrointestinal inflammation, gastrointestinal hemorrhage, gastrointestinal ulcer, and gastrointestinal perforation; severity may range from asymptomatic to fatal (Ref). Selective cyclooxygenase (COX)-2 NSAIDs, including celecoxib, appear to be associated with a lower risk of significant GI adverse events as compared to nonselective NSAIDs (Ref); the concomitant use of low-dose aspirin therapy may diminish the safety advantage of COX-2 selective NSAIDs over nonselective NSAIDs (Ref).
Mechanism: Dose- and time-related; inhibition of COX-1 by NSAIDs results in a reduction in the production of mucosal-protective prostaglandin E2). COX-2 selective NSAIDs may block COX-1 in the GI tract, albeit to a lesser degree as compared to nonselective NSAIDs, and therefore have the ability to cause damage (Ref).
Onset: Varied; GI events can occur at any time during use and without warning symptoms.
Risk factors:
• ≥65 years of age (Ref)
• Longer duration of use
• Higher doses (eg, celecoxib 400 mg twice daily (Ref))
• Prior history of peptic ulcer disease and/or GI bleeding
• Concomitant use of agents known to increase the risk of GI bleeding (eg, aspirin (Ref); anticoagulants, corticosteroids (Ref); selective serotonin reuptake inhibitors (Ref))
• Comorbid Helicobacter pylori infection (Ref)
• Advanced liver disease/cirrhosis
• Coagulopathy
• Smoking
• Consumption of alcohol
• People with poor general health status
• Small intestine damage: Small intestine bacterial overgrowth (SIBO), including SIBO induced by proton pump inhibitor therapy, may be associated with an increased risk of small intestine damage (Ref)
Use of celecoxib may result in anemia (Ref). Although no cases of drug-induced hemolytic anemia associated with celecoxib use have been reported, this adverse event has been reported with other nonsteroidal anti-inflammatory drugs (NSAIDs), including both non-selective and cyclooxygenase (COX)-2 selective agents (Ref). While nonselective NSAIDs (eg, ibuprofen) may cause prolonged bleeding time and an increased risk for hemorrhage, COX-2 selective NSAIDS (eg, celecoxib), are less likely to result in abnormal platelet function or prolonged bleeding time (Ref).
Mechanism:
Anemia: Not clearly established; anemia may be due to occult or gross blood loss, or in some cases, drug-induced antibodies leading to autoimmune hemolysis.
Prolonged bleeding time: Inhibition of COX-1 causes a decrease in the production of prostaglandins, prostacyclins, and thromboxanes, including thromboxane A2 (TxA2) (Ref). Therefore, patients exposed to NSAIDs, especially nonselective NSAIDs (eg, naproxen), may exhibit a decrease in platelet adhesion and aggregation and subsequent prolonged bleeding time (Ref).
Onset: Prolonged bleeding time: Rapid; suppression of platelet COX-1 activity occurs within hours of administration (Ref). In patients receiving antithrombotic therapy after myocardial infarction, the use of NSAIDs, including COX-2 selective NSAIDs (eg, celecoxib), has been associated with an increased risk of bleeding and excess thrombotic events even after short-term treatment (eg, <3 days) (Ref).
Risk factors:
• Bleeding events:
- Preexisting coagulation disorders
- Concomitant use of agents known to increase the risk of bleeding (eg, anticoagulants (Ref); antithrombotics (Ref); antiplatelet agents [eg, aspirin, clopidogrel (Ref)]; selective serotonin reuptake inhibitors (Ref); or serotonin norepinephrine reuptake inhibitors)
Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including celecoxib, may result in mild and transient transaminase elevations. The incidence of hepatic adverse events appears similar between celecoxib, naproxen, and ibuprofen (Ref); diclofenac exhibits a higher rate of hepatotoxic events as compared to other NSAIDs (Ref). Rarely, use of celecoxib has resulted in acute hepatitis and drug-induced liver injury (DILI) with a hepatocellular, cholestatic, or mixed pattern of liver injury; celecoxib-induced liver injury requiring liver transplantation has been described (Ref). The pattern of celecoxib-induced liver injury may resemble sulfonamide-induced livery injury (ie, short latency and abrupt onset) and cross-reactivity has been described (Ref).
Mechanism: Not clearly established; some cases may exhibit immunoallergic features similar to sulfonamide-induced liver injury (Ref).
Onset: DILI: Varied; cases with immunoallergic features may occur after a short duration of treatment (median: 12 days; range: 1 to 42), whereas cases without immunoallergic features may occur following prolonged use (6 months to 2 years) (Ref).
Risk factors:
• Prior sulfonamide-induced liver injury (Ref)
Immediate (eg, anaphylaxis, urticaria/angioedema) (Ref) and delayed hypersensitivity reactions have been reported with celecoxib. Delayed hypersensitivity reactions include mild reactions such as maculopapular rash and fixed drug eruption (Ref); severe cutaneous adverse reactions (SCARs) including acute generalized exanthematous pustulosis (Ref), Stevens-Johnson syndrome/toxic epidermal necrolysis (Ref) and drug rash with eosinophilia and systemic symptoms (Ref) have been documented. Vasculitis of the skin has also been reported (Ref).
Mechanism: Non–dose-related; immunologic. Immediate hypersensitivity reactions (eg, anaphylaxis, urticaria) are typically IgE-mediated (Ref). Delayed hypersensitivity reactions, including maculopapular eruptions, fixed drug eruption, and SCARs, are thought to be T-cell-mediated (Ref).
Onset:
Immediate hypersensitivity reactions: Rapid; occur within 1 hour of administration but may occur several hours after exposure (Ref).
Delayed hypersensitivity reactions:
Maculopapular reactions: Intermediate; typically occur 7 to 14 days after initiation (Ref).
Other reactions (including SCARs): Varied; occur 1 to 8 weeks after initiation (Ref). Vasculitis of the skin has been reported 3 to 4 days after initiating therapy (Ref).
Risk factors:
• Selective cyclooxygenase (COX)-2 inhibitors (eg, celecoxib) are generally tolerated in patients with NSAID-exacerbated respiratory disease (NERD) (Ref), patients with histories of isolated respiratory reaction to NSAIDs (Ref), and in many patients with cutaneous reactions to NSAIDs (Ref); however, cross-reactions may occur, especially in patients with histories of urticaria/angioedema (Ref).
• There is limited published information regarding possible cross-reactivity between celecoxib and other sulfonamides (Ref). Cross-reactivity between celecoxib, a nonantibiotic sulfonamide, and antibiotic sulfonamides is unlikely to occur (Ref).
• Cross-reactivity among COX-2 inhibitors is not known, although there are reports of patients who have tolerated celecoxib following a reaction to etoricoxib (Ref). Cross-reactivity with nabumetone has been reported (Ref).
Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including celecoxib, is associated with an increased risk of several kidney-specific effects: Hemodynamically-mediated acute kidney injury (AKI), interstitial nephritis (with or without nephrotic syndrome), and renal papillary necrosis.
Hemodynamically-mediated AKI: Hemodynamically-mediated AKI may occur following use of either cyclooxygenase (COX)-2 selective NSAIDs, including celecoxib, or nonselective NSAIDs (eg, naproxen) (Ref); the risk may be greater with nonselective NSAIDs, especially indomethacin (Ref). The risk of developing AKI is decreased upon discontinuation (Ref). In patients who develop AKI, kidney function is likely to return to baseline following prompt discontinuation of the offending NSAID and supportive care (Ref); however, the mechanism of the damage and other concurrent factors can contribute to irreversibility.
Acute interstitial nephritis (AIN) with or without nephrotic syndrome: Patients may develop NSAID-associated proteinuria combined with interstitial nephritis and varying degrees of kidney impairment; the “classic triad” of fever, rash, and eosinophilia is less commonly observed in NSAID-associated AIN than with antibiotic-induced AIN (Ref). In patients with concurrent nephrotic syndrome, kidney histology may reveal minimal change glomerulonephritis or membranous nephropathy (Ref). While use of celecoxib has been associated with this clinical picture (Ref), the risk may be greatest with fenoprofen as compared to other NSAIDS (Ref). Proteinuria generally improves within weeks following discontinuation; full recovery may require treatment and take up to a year (Ref).
Papillary necrosis: Chronic use of NSAIDs, including celecoxib, has resulted in the development of papillary necrosis which may occur in conjunction with chronic interstitial nephritis and progressive decline in glomerular filtration rate as a clinical syndrome known as analgesic nephropathy (Ref). However, controversy exists on the degree to which NSAID use increases the risk for chronic kidney disease and analgesic nephropathy (Ref). Acute papillary necrosis may occur following NSAID overdose, especially in a setting of severe dehydration or intravascular volume depletion (Ref).
Mechanism:
Hemodynamically-mediated AKI: Dose- and time-related; inhibition of COX-1 and COX-2 by NSAIDs results in a reduced production of nephroprotective prostaglandins and subsequent attenuation of renal vasodilation (Ref). In addition, an increase in vasoconstriction of the afferent arteriole and impaired renal blood flow causes a reduction in the glomerular capillary pressure and filtration (Ref).
AIN with or without nephrotic syndrome: Not clearly established. Following inhibition of COX-1 and COX-2 by NSAIDs, arachidonic acid is formed which may be further metabolized to leukotrienes via the lipoxygenase pathway; leukotrienes may increase vascular permeability within glomerular capillaries and peritubular capillaries and increase lymphocyte recruitment and activation (Ref).
Papillary necrosis: Time-related; exact mechanism is not clearly established; may be due to direct toxicity and/or inhibition of prostaglandin-mediated vasodilation resulting in ischemic necrosis (Ref).
Onset:
AKI: Rapid; may occur within days of treatment initiation (Ref).
AIN with or without nephrotic syndrome: Varied; mean time of onset of ~5 months (range: 2 weeks to 18 months) has been described following use of nonselective NSAIDs (Ref).
Risk factors:
• AKI:
- Preexisting kidney impairment
- Chronic kidney disease (Ref). Note: Higher cumulative doses (eg, celecoxib >100 mg/day) may increase the risk for progression of chronic kidney disease (Ref)
- ≥65 years of age (Ref). Note: NSAID-associated AKI may also occur in pediatric patients, even at therapeutic doses (Ref)
• Hemodynamically-mediated AKI:
- Preexisting conditions which result in decreased effective arterial circulation (ie, conditions where renal blood flow/renal perfusion may be dependent on prostaglandin-mediated vasodilation) (Ref)
Volume depletion (eg, due to concomitant diuretic use, nausea, or vomiting)
Heart failure (Ref)
Cirrhosis and ascites (Ref)
Nephrotic syndrome
- Concomitant use of diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or calcineurin inhibitors (Ref)
• AIN with or without nephrotic syndrome: Prior history of NSAID-induced nephrotic syndrome; recurrence has been described with a nonselective NSAID (Ref)
• Papillary necrosis (acute):
- Massive NSAID ingestion (Ref)
- Dehydration (Ref)
- Intravascular volume depletion (Ref)
• Papillary necrosis (chronic)/analgesic nephropathy: Chronic concomitant use of other analgesics (eg, aspirin, acetaminophen) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Cardiovascular: Acute myocardial infarction (<2%), angina pectoris (<2%), chest pain (<2%), coronary artery disease (<2%), edema (<2%), exacerbation of hypertension (<2%), palpitations (<2%), peripheral edema (2%), tachycardia (<2%)
Dermatologic: Alopecia (<2%), cellulitis (<2%), contact dermatitis (<2%), dermatitis (<2%), diaphoresis (<2%), ecchymoses (<2%), erythematous rash (<2%), maculopapular rash (<2%), pruritus (<2%), skin changes (<2%), skin photosensitivity (<2%), urticaria (<2%), xeroderma (<2%)
Endocrine & metabolic: Albuminuria (<2%), hot flash (<2%), hypercholesterolemia (<2%), hyperglycemia (<2%), hypokalemia (<2%), increased nonprotein nitrogen (<2%), weight gain (<2%)
Gastrointestinal: Abdominal pain (4%), anorexia (<2%), constipation (<2%), diarrhea (6%), diverticulitis of the gastrointestinal tract (<2%), dysgeusia (3%), dyspepsia (9%), dysphagia (<2%), eructation (<2%), esophagitis (<2%), flatulence (2%), gastritis (<2%), gastroenteritis (<2%), gastroesophageal reflux disease (<2%), hemorrhoids (<2%), hiatal hernia (<2%), increased appetite (<2%), melena (<2%), stomatitis (<2%), tenesmus (<2%), vomiting (<2%), xerostomia (<2%)
Genitourinary: Cystitis (<2%), dysuria (<2%), hematuria (<2%), urinary frequency (<2%)
Hematologic & oncologic: Anemia (<2%), thrombocythemia (<2%)
Hepatic: Increased liver enzymes (<3 x ULN: ≤6%), increased serum alkaline phosphatase (<2%)
Hypersensitivity: Facial edema (<2%), hypersensitivity reaction (<2%)
Nervous system: Anxiety (<2%), depression (<2%), drowsiness (<2%), fatigue (<2%), hypertonia (<2%), hypoesthesia (<2%), migraine (<2%), nervousness (<2%), pain (<2%), paresthesia (<2%), peripheral pain (<2%), vertigo (<2%)
Neuromuscular & skeletal: Arthralgia (<2%), increased creatine phosphokinase in blood specimen (<2%), lower limb cramp (<2%), myalgia (<2%), synovitis (<2%), tendinopathy (<2%)
Otic: Deafness (<2%), tinnitus (<2%)
Renal: Increased blood urea nitrogen (<2%), increased serum creatinine (<2%), nephrolithiasis (<2%)
Respiratory: Aggravated bronchospasm (<2%), bronchitis (<2%), bronchospasm (<2%), cough (<2%), dyspnea (<2%), epistaxis (<2%), flu-like symptoms (<2%), laryngitis (<2%), pharyngitis (2%), pneumonia (<2%), rhinitis (2%), sinusitis (5%), upper respiratory tract infection (8%)
Miscellaneous: Cyst (<2%), fever (<2%)
<1%:
Cardiovascular: Heart failure, pulmonary embolism, syncope, thrombophlebitis, ventricular fibrillation
Dermatologic: Gangrene of skin and/or subcutaneous tissue
Gastrointestinal: Cholelithiasis, esophageal perforation, gastrointestinal hemorrhage, hemorrhagic colitis, intestinal obstruction, intestinal perforation, pancreatitis
Hematologic & oncologic: Thrombocytopenia
Infection: Sepsis
Nervous system: Ataxia, cerebrovascular accident, suicidal tendencies
Renal: Acute kidney injury
Frequency not defined:
Cardiovascular: Coronary thrombosis
Dermatologic: Erythema multiforme, exfoliative dermatitis
Gastrointestinal: Alveolar osteitis (post-oral surgery patients), gastrointestinal inflammation, gastrointestinal perforation, gastrointestinal ulcer
Postmarketing:
Cardiovascular: Acute coronary syndrome (Kounis syndrome) (Regis 2015), deep vein thrombosis (Chan 2005), hypertension (Handler 2003), vasculitis (allergic) (Schneider 2002)
Dermatologic: Acute generalized exanthematous pustulosis (Goeschke 2004; Lee 2016), Stevens-Johnson syndrome (La Grenade 2005), toxic epidermal necrolysis (Berger 2002; Friedman 2002; Perna 2003), vasculitis of the skin (Drago 2004)
Endocrine & metabolic: Hypoglycemia, hyponatremia
Gastrointestinal: Ageusia
Hematologic & oncologic: Agranulocytosis, aplastic anemia, leukopenia, pancytopenia
Hepatic: Cholestasis (Chamouard 2005), hepatic failure (El Hajj 2009), hepatic necrosis, hepatitis (including cholestatic hepatitis) (Larrey 2019), jaundice (Chamouard 2005)
Hypersensitivity: Anaphylaxis (Chamberlin 2009), angioedema (Gagnon 2003), drug reaction with eosinophilia and systemic symptoms (Lee 2008), fixed drug eruption (Ammar 2019), nonimmune anaphylaxis
Nervous system: Anosmia, aseptic meningitis (Papaioannides 2004), intracranial hemorrhage
Renal: Interstitial nephritis (Henao 2002), renal papillary necrosis (Akhund 2003)
Hypersensitivity (eg, anaphylaxis, serious skin reactions) to celecoxib, sulfonamides, aspirin, other NSAIDs, or any component of the formulation; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; use in the setting of CABG surgery.
Note: Although the FDA-approved product labeling states this medication is contraindicated in patients with hypersensitivity to sulfonamide-containing drugs, the scientific basis of this cross-sensitivity has been challenged. See “Warnings/Precautions” for more detail.
Canadian labeling: Additional contraindications (not in US labeling): Pregnancy (third trimester); women who are breast-feeding; severe, uncontrolled heart failure; active gastrointestinal ulcer (gastric, duodenal, peptic); active gastrointestinal bleeding; inflammatory bowel disease; cerebrovascular bleeding; severe liver impairment or active hepatic disease; severe renal impairment (CrCl <30 mL/minute) or deteriorating renal disease; known hyperkalemia; use in patients <18 years of age
Concerns related to adverse effects:
• Medication-overuse headache: Acute migraine agents used more frequently than recommended (eg, >14 days per month) may lead to worsening of headaches (medication-overuse headache). Symptoms include migraine-like daily headaches or a marked increase in frequency of migraine attacks. Withdrawal treatment may be necessary in the setting of overuse (AHS [Ailani 2021]; manufacturer’s labeling).
• Sulfonamide ("sulfa") allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are not well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (SJS/TEN), some clinicians choose to avoid exposure to these classes.
Disease-related concerns:
• Asthma: The manufacturer's labeling states to not administer to patients with aspirin-sensitive asthma due to severe and potentially fatal bronchospasm that has been reported in such patients having received aspirin and the potential for cross reactivity with other NSAIDs. The manufacturer also states to use with caution in patients with other forms of asthma. However, in patients with known aspirin-exacerbated respiratory disease (AERD), the use of celecoxib initiated at a low dose with gradual titration in patients with stable, mild to moderate persistent asthma has been used without incident (Morales 2013).
• 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).
• Cytochrome P450 isoenzyme 2C9 deficiency: Use with caution in patients with known or suspected deficiency of cytochrome P450 isoenzyme 2C9 (CYP 2C9*3/*3); poor metabolizers may have higher plasma levels due to reduced metabolism; consider reduced initial doses (initiate therapy with 25% to 50% of the lowest starting dose [eg, 50% to 75% dose reduction]) (CPIC [Theken 2020]). Alternate therapies should be considered in patients with juvenile idiopathic arthritis (JIA) who are poor metabolizers of CYP2C9.
• Hepatic impairment: Use with caution in patients with moderate hepatic impairment; dosage adjustment recommended. Not recommended for patients with severe hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
Special populations:
• Pediatric: Use with caution in pediatric patients with systemic-onset JIA; serious adverse reactions, including disseminated intravascular coagulation, may occur. Long-term cardiovascular risk in children has not been evaluated.
Consider alternate therapy in JIA patients who are identified to be CYP2C9 poor metabolizers. In a small pediatric study (n=4), the AUC of celecoxib was ~10 times higher in a child who was homozygous for CYP2C9*3, compared to children who were homozygous for the *1 allele (n=2) or who had the CYP2C9*1/*2 genotype; further studies are needed to determine if carriers of the CYP2C9*3 allele are at increased risk for cardiovascular toxicity or dose related adverse effects of celecoxib, especially with long-term, high-dose use of the drug (Stempak 2005).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
CeleBREX: 50 mg, 100 mg, 200 mg, 400 mg
Generic: 50 mg, 100 mg, 200 mg, 400 mg
Solution, Oral:
Elyxyb: 120 mg/4.8 mL (4.8 mL) [contains alcohol, usp, levomenthol, peg-40 hydrog castor oil(cremophor rh40), polyoxyl/peg-35 castor oil(cremophor el)]
Elyxyb: 120 mg/4.8 mL (4.8 mL) [contains alcohol, usp, levomenthol, peg-40 hydrog castor oil(cremophor rh40), polyoxyl/peg-35 castor oil(cremophor el); peppermint flavor]
May be product dependent
Capsules (CeleBREX Oral)
50 mg (per each): $5.61
100 mg (per each): $12.01
200 mg (per each): $19.70
400 mg (per each): $29.55
Capsules (Celecoxib Oral)
50 mg (per each): $0.06 - $2.16
100 mg (per each): $0.06 - $4.62
200 mg (per each): $0.07 - $7.58
400 mg (per each): $0.81 - $11.37
Solution (Elyxyb Oral)
120MG/4.8ML (per mL): $36.45
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.
Capsule, Oral:
CeleBREX: 100 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
CeleBREX: 200 mg
Generic: 100 mg, 200 mg
Oral:
May be administered without regard to meals.
Capsules: May be swallowed whole or the entire contents emptied onto a teaspoon of cool or room temperature applesauce and administered immediately with water. The contents of the capsules sprinkled onto applesauce may be stored under refrigeration for up to 6 hours.
Oral solution: Administer full dose directly from bottle. Administer partial dose with a calibrated measuring device (not a household teaspoon or tablespoon).
Oral: Lower doses may be administered without regard to meals (may administer with food to reduce GI upset); larger doses should be administered with food to improve absorption. Capsules may be swallowed whole or the entire contents emptied onto a teaspoon of cool or room temperature applesauce and ingested immediately with water. The sprinkled contents of the capsule on applesauce may be stored under refrigeration for up to 6 hours.
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.accessdata.fda.gov/drugsatfda_docs/label/2018/020998s050lbl.pdf#page=21
Anti-inflammatory: Relief of the signs/symptoms of ankylosing spondylitis or rheumatoid arthritis.
Dysmenorrhea: Treatment of primary dysmenorrhea.
Juvenile idiopathic arthritis: Relief of the signs/symptoms of juvenile idiopathic arthritis (JIA) in patients 2 years and older.
Migraine, acute treatment: Acute treatment of migraine with or without aura in adults.
Osteoarthritis: Relief of the signs/symptoms of osteoarthritis.
Pain, acute: Management of acute pain.
Gout, treatment, acute flares; Pain, chronic
CeleBREX may be confused with CeleXA, Cerebyx, Cervarix, Clarinex
Substrate of CYP2C9 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak)
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 enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives. Risk C: Monitor therapy
Acemetacin: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. 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. 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: Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Aspirin: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Specifically, the risk of gastrointestinal adverse effects may be increased. Management: Concurrent use of aspirin at doses beyond cardioprotective levels is not recommended. While concurrent use of low-dose aspirin with a COX-2 inhibitor is permissible, patients should be monitored closely for signs/symptoms of GI ulceration/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
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
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
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). 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 Celecoxib. Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Celecoxib. Risk C: Monitor therapy
Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. 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
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Drospirenone-Containing Products: May enhance the hyperkalemic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
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
Estrogen Derivatives: Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may enhance the thrombogenic effect of Estrogen Derivatives. Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may increase the serum concentration of Estrogen Derivatives. 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
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk C: Monitor therapy
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy
Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Ketorolac (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Ketorolac (Systemic). Risk X: Avoid combination
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Management: Consider reducing the lithium dose when initiating a NSAID. Monitor for increased lithium therapeutic/toxic effects if a NSAID is initiated/dose increased, or decreased effects if a NSAID is discontinued/dose decreased. Risk D: Consider therapy modification
Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
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
Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. 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: 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 enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Mifamurtide: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide. Risk X: Avoid combination
Naftazone: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk for gastrointestinal toxicity is increased. Risk X: Avoid combination
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect 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
Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Risk C: Monitor therapy
Phenylbutazone: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Polyethylene Glycol-Electrolyte Solution: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Potassium Salts: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium Salts. 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: 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
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor for signs of methemoglobinemia when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid use of these agents with prilocaine/lidocaine cream in infants less than 12 months of age. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. 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
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. 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 Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy
Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
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 due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. 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
Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider therapy modification
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: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Tricyclic Antidepressants may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Triflusal: Nonsteroidal Anti-Inflammatory Agents may decrease the protein binding of Triflusal. Specifically, NSAIDs may decrease protein binding of the active Triflusal metabolite. Triflusal may decrease the protein binding of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
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
Peak concentrations are delayed when taken with a high-fat meal. Management: Administer without regard to meals.
Capsules: AUC is increased by 10% to 20% when taken with a high-fat meal.
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 patients 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 (FDA 2020). Because NSAIDs may cause premature closure of the ductus arteriosus, product labeling for celecoxib 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]).
Treatment for migraine headaches in pregnant patients should be individualized (AHS [Ailani 2021]). The acute treatment of migraine headaches during pregnancy should be initiated with an agent other than an NSAID. If an NSAID is needed as second-line therapy, treatment should be limited to the second trimester and total duration of therapy should be no longer than 48 hours. An NSAID other than celecoxib may be preferred (ACOG 2022).
NSAIDs may be used as part of a multimodal approach to pain relief following cesarean delivery (ACOG 2019).
Celecoxib is present in breast milk.
Data related to the presence of celecoxib in breast milk are available from multiple studies.
• Breast milk was sampled at intervals over 48 hours in 6 women, 6.5 to 15 months postpartum, following a single dose of celecoxib 200 mg. Peak breast milk concentrations (0.07 to 0.33 mg/L) occurred between 2 and 4 hours after the dose. Authors of the study calculated the estimated infant dose of celecoxib via breast milk to be 0.011 to 0.21 mg/kg/day providing a relative infant dose (RID) of 0.17% to 0.3% (Gardiner 2006).
• The transfer of celecoxib into breast milk was evaluated in 5 breastfeeding women who ranged from 3 to 22 months postpartum. Breast milk samples were collected over a period of 24 hours from 3 women taking celecoxib 200 mg/day for several weeks. Plasma concentrations were collected 4 hours after the dose in 2 breastfeeding infants. Maximum celecoxib concentrations averaged 0.139 mg/L and were reached in breast milk ~2 to 3 hours after the dose. Celecoxib breast milk concentrations were below the limit of detection (<0.010 mg/L) at 12 and 24 hours; infant plasma concentrations were also below the limit of detection. Two additional women were given a single dose of celecoxib 200 mg and breast milk and venous blood samples were collected over a period of 8 hours. Breast milk and maternal concentrations peaked at 2 to 4 hours. The maximum breast milk concentrations of celecoxib were 0.17 mg/L and 0.269 mg/L. The average concentration of celecoxib in breast milk among all 5 women ranged from 0.038 to 0.083 mg/L (mean 0.66 mg/L) over the course of 8 hours. Using the average breast milk concentration, the authors calculated the estimated infant dose via breast milk to be 0.0098 mg/kg/day providing a relative infant dose (RID) of 0.3% (Hale 2004).
• Breast milk was sampled in one lactating woman 5 months postpartum who took celecoxib 100 mg twice daily for 4 doses following an appendectomy. The highest concentration was 0.133 mg/L, which occurred 4.75 hours following her last dose. Authors of the study calculated the estimated infant dose of celecoxib via breast milk to be 0.02 mg/kg/day. The half-life of celecoxib in breast milk was calculated to be 4 to 6.5 hours (Knoppert 2003).
• In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
Adverse events were not observed in 2 breastfeeding infants 17 and 22 months of age (Hale 2004).
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]) and short-term use of celecoxib is considered acceptable (ABM [Reece-Stremtan 2017]). NSAIDs are considered compatible for the treatment of rheumatic and musculoskeletal diseases in lactating patients; agents with a short half-life and established safety data in infants may be preferred (ACR [Sammaritano 2020]). NSAIDs may be used to treat acute migraine in lactating patients (ACOG 2022).
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 (periodically throughout treatment); hemoglobin/hematocrit (during long-term therapy; anemic patients); basic metabolic panel (periodically throughout treatment); occult blood loss; signs/symptoms of liver disease, including periodic LFTs; renal function (urine output, serum BUN and creatinine); therapeutic response (pain, range of motion, grip strength, mobility, ADL function), inflammation; blood pressure (baseline and during treatment); weight gain, edema; bleeding, bruising; GI effects (abdominal pain, bleeding, dyspepsia); signs of immediate or delayed hypersensitivity reactions.
JIA: Monitor for development of abnormal coagulation tests with systemic onset JIA.
Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase-2 (COX-2), which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties. Celecoxib does not inhibit cyclooxygenase-1 (COX-1) at therapeutic concentrations.
Absorption:
Capsule: Prolonged due to low solubility.
Oral solution: Rapid (Pal 2017).
Distribution: Vd (apparent):
Capsule: Children and Adolescents ~7 to 16 years (steady-state): 8.3 ± 5.8 L/kg (Stempak 2002); Adults: ~400 L.
Oral solution: Adults: ~288 to 743 L (Pal 2017; manufacturer’s labeling).
Protein binding: ~97% primarily to albumin; binds to alpha1-acid glycoprotein to a lesser extent.
Metabolism: Hepatic via CYP2C9; forms inactive metabolites (a primary alcohol, corresponding carboxylic acid, and its glucuronide conjugate).
Bioavailability:
Capsule: Absolute: Unknown.
Oral solution: 144% (relative to capsule) (Pal 2017).
Half-life elimination:
Capsule: Children and Adolescents ~7 to 16 years (steady-state): 6 ± 2.7 hours (range: 3 to 10 hours) (Stempak 2002); Adults: ~11 hours (fasted).
Oral solution: Adults: ~4.5 to 6 hours (Pal 2017; manufacturer’s labeling).
Time to peak:
Capsule: Children: Median: 3 hours (range: 1 to 5.8 hours) (Stempak 2002); Adults: ~3 hours.
Oral solution: Adults: 0.7 to 1 hour (Pal 2017; manufacturer’s labeling).
Excretion: Feces (~57% as metabolites, <3% as unchanged drug); urine (27% as metabolites, <3% as unchanged drug); primary metabolites in feces and urine: Carboxylic acid metabolite (73% of dose); low amounts of glucuronide metabolite appear in urine.
Altered kidney function: Capsule: AUC is approximately 40% lower in patients with a CrCl of 35 to 60 mL/minute.
Hepatic function impairment: Capsule: AUC is increased approximately 40% in patients with mild impairment (Child-Pugh class A) and 180% in patients with moderate impairment (Child-Pugh class B).
Pediatric: The AUC and Cmax following administration of a capsule contents sprinkled on applesauce were reported to be similar as administration of an intact capsule (Krishnaswami 2012).
Older adult (>65 years of age): Capsule: Cmax is 40% higher and AUC is 50% higher.
Race/ethnicity: Capsule: AUC is approximately 40% higher in Black patients compared with White patients.
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