Celecoxib

Article Author:
Brandon Cohen
Article Editor:
Charles Preuss
Updated:
5/17/2019 3:50:05 PM
PubMed Link:
Celecoxib

Indications

Celecoxib has numerous indications, both FDA approved, and non-FDA approved.

The FDA recommends celecoxib and other NSAIDs (non-steroidal anti-inflammatory drugs), along with acetaminophen, as first-line analgesics for patients with osteoarthritis and rheumatoid arthritis. Celecoxib also has an FDA indication for the management of acute pain in adult women and primary dysmenorrhea. Furthermore, the FDA also recommends the use of celecoxib as an adjunct therapy in patients with familial adenomatous polyposis to reduce the number of colorectal polyps.[1]

Off-label, celecoxib can be used for a wide variety of musculoskeletal and rheumatologic conditions including ankylosing spondylitis, juvenile idiopathic arthritis, and gout. It is also being used increasingly in hospital protocols as part of a multimodal perioperative pain management regimen, frequently given pre-operatively along with adjunct pain medications including acetaminophen and/or pregabalin.[2]

Mechanism of Action

Celecoxib is chemically designated as 4-[5-(4-methylphenyl)- 3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide and is a diaryl-substituted pyrazole. The mechanism of action of celecoxib is due to selective inhibition of cyclooxygenase-2 (COX-2) which is responsible for prostaglandin synthesis, an integral part of the pain and inflammation pathway.[3] This activity gives celecoxib its analgesic, anti-inflammatory, and antipyretic activity. Celecoxib does weakly inhibit COX-1 and therefore, may affect platelet function to a lesser extent.

Celecoxib also has anticancer properties discussed below and exerts its anticancer properties by binding cadherin-11 (CDH11) which likely plays a significant role in malignant progression of cancerous cells.[4]

Celecoxib is extensively metabolized through cytochrome P450 2C9 (CYP2C9) and may have interactions with other medications that are substrates of CYP2C9.[5]

Administration

Celecoxib is a medication that is taken orally and comes in 50-, 100-, 200-, and 400-mg doses. In rare cases, celecoxib can also be added to customized compounds for topical administration with or without the use of iontophoresis or other topical delivery mechanisms. It is not available via any other route of administration.

Adverse Effects

Like all NSAIDs, celecoxib carries an FDA boxed warning for cardiovascular risk including the increased risk of heart attacks and strokes. As a selective COX-2 inhibitor, celecoxib also faces scrutiny for increased cardiovascular risk, since another selective COX-2 inhibitor, rofecoxib, was withdrawn from production in 2004 due to cardiovascular risk concerns. Large reviews have had mixed results regarding whether celecoxib carries non-inferior or increased cardiovascular risk compared to ibuprofen and naproxen.[6][7]

Also like all NSAIDs, celecoxib carries an additional FDA boxed warning for gastrointestinal (GI) effects including bleeding, ulceration, and perforation of the stomach and intestines. This adverse effect makes it particularly dangerous to susceptible populations such as the elderly.

In addition to these, celecoxib may cause new or worsening hypertension, fluid retention in patients with congestive heart failure, renal toxicity, liver toxicity, anaphylactic reactions, and skin changes ranging from a non-severe rash to Stevens-Johnson syndrome.

Contraindications

Due to its cardiovascular risk, celecoxib is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graph (CABG) surgery.

Celecoxib also contains a sulfonamide group and is contraindicated in patients who have demonstrated severe allergic reactions to sulfonamide drugs. Studies have shown that allergies to sulfonamide antimicrobials are indeed a risk factor for allergic reactions to sulfonamide chemical group. Non-antimicrobial drugs which contain a sulfonamide chemical group such as celecoxib, a history of penicillin allergy is at least as strong a risk factor for an allergic reaction. Thus, providers should understand that this phenomenon is likely not due to sole cross-reactivity of sulfonamide-containing antimicrobials and non-antimicrobials and that certain patients have an increased propensity to celecoxib allergy if they are allergic to any antimicrobial drug.[8]

Since CYP2C9 metabolizes celecoxib, it should be used with caution in patients taking medicines that inhibit CYP2C9, for example, fluconazole which is an antifungal drug.[5]

Like all NSAIDs, celecoxib should not be taken after 29 weeks of pregnancy.

Monitoring

Due to the risk for celecoxib to cause new or worsening hypertension, fluid retention in patients with congestive heart failure, renal toxicity, liver toxicity, anaphylactic reactions, and skin changes ranging from a non-severe rash to Stevens-Johnson syndrome, it is important for prescribers to monitor patients for adverse drug reactions. Prescribers should monitor a patient's blood pressure, renal and liver function, and monitor for signs and symptoms of GI bleeding.

Patients taking such medications as lithium or warfarin should have the concentrations of these drugs monitored more closely as well due to celecoxib's renal toxicity and inhibition of CYP2C9, respectively. Plasma concentrations of celecoxib are not routinely monitored for therapeutic efficacy.

Toxicity

Unfortunately, no antidotes for celecoxib overdose are available. However, celecoxib is a relatively safe medication overall. During FDA trials, no overdoses of celecoxib were reported. Doses up to 2400 mg per day for 10 days did not result in serious toxicity.

Symptoms of celecoxib overdose would likely be similar to overdoses of other NSAIDs which include lethargy, drowsiness, nausea, vomiting, and epigastric pain. Activated charcoal may be administered for overdose treatment at the discretion of emergency medical providers if the patient presents within 4 hours of known or suspected ingestion of significant amounts of celecoxib. Due to high plasma protein binding, dialysis, urine alkalinization, or diureses are unlikely to have a significant therapeutic effect on celecoxib overdose.

Enhancing Healthcare Team Outcomes

Significant opportunities are available for improved interprofessional care coordination with regards to celecoxib.

In the inpatient setting, as mentioned above, celecoxib is increasingly being used as part of pre-operative and post-operative multimodal pain management algorithms. It has been shown in several small randomized trials that administering celecoxib peri-operatively for elective procedures such as total hip arthroplasties, total knee arthroplasties, and other procedures with some success in reducing pain and improving functionality such as early ambulation. The use of non-opioid medications to improve pain and function after surgery is becoming increasingly important due to societal and political pressure to reduce overall opioid analgesic consumption as a response to increasing rates of overdose deaths. It is therefore important for physicians, nurses, pharmacists, physical and occupational therapists, and other support staff to coordinate a concerted effort to set patient-specific goals regarding pain and function in the acute care and rehabilitative settings and to reinforce how celecoxib can be used to achieve these goals to the patient. Physicians and support staff must also maintain constant communication while monitoring the patient for improvements in pain and function and for possible adverse effects the patient may be experiencing.

In the outpatient setting, prescribers of celecoxib must also coordinate with pharmacists to prevent and monitor for unsafe drug interactions, and with the patient, family members, and caregivers to monitor therapeutic benefit and possible adverse drug effects.


References

[1] Tolloczko-Iwaniuk N,Dziemianczyk-Pakiela D,Nowaszewska BK,Celinska-Janowicz K,Miltyk W, Celecoxib in Cancer Therapy and Prevention - Review. Current drug targets. 2018 Aug 3;     [PubMed PMID: 30073924]
[2] Pitchon DN,Dayan AC,Schwenk ES,Baratta JL,Viscusi ER, Updates on Multimodal Analgesia for Orthopedic Surgery. Anesthesiology clinics. 2018 Sep;     [PubMed PMID: 30092934]
[3] McAdam BF,Catella-Lawson F,Mardini IA,Kapoor S,Lawson JA,FitzGerald GA, Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proceedings of the National Academy of Sciences of the United States of America. 1999 Jan 5     [PubMed PMID: 9874808]
[4] Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: common target, common therapies., Assefnia S,Dakshanamurthy S,Guidry Auvil JM,Hampel C,Anastasiadis PZ,Kallakury B,Uren A,Foley DW,Brown ML,Shapiro L,Brenner M,Haigh D,Byers SW,, Oncotarget, 2014 Mar 30     [PubMed PMID: 24681547]
[5] Wang B,Wang J,Huang SQ,Su HH,Zhou SF, Genetic polymorphism of the human cytochrome P450 2C9 gene and its clinical significance. Current drug metabolism. 2009 Sep     [PubMed PMID: 19925388]
[6] Nissen SE, Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. The New England journal of medicine. 2017 Apr 6     [PubMed PMID: 28379793]
[7] Barcella CA,Lamberts M,McGettigan P,Fosbøl EL,Lindhardsen J,Torp-Pedersen C,Gislason GH,Olsen AS, Differences in cardiovascular safety with non-steroidal anti-inflammatory drug therapy - a nationwide study in patients with osteoarthritis. Basic     [PubMed PMID: 30484960]
[8] Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics., Strom BL,Schinnar R,Apter AJ,Margolis DJ,Lautenbach E,Hennessy S,Bilker WB,Pettitt D,, The New England journal of medicine, 2003 Oct 23     [PubMed PMID: 14573734]