Criteria for Outpatient Use Guidelines

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[Developed, January 2002; January 2003; January 2004; January 2006; February 2006; October 2007;
January 2011; March 2011]
MEDICAID DRUG USE REVIEW CRITERIA FOR OUTPATIENT USE

Information on indications for use or diagnosis is assumed to be unavailable.  All criteria may be applied retrospectively; prospective application is indicated with [*].

1.* Dosage

Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor nonsteroidal anti-inflammatory drug (NSAID) that demonstrates anti-inflammatory, analgesic and antipyretic effects through inhibiting prostaglandin synthesis, predominantly by inhibiting COX-2.  Unlike nonselective NSAIDs, the production of thromboxane A, a potent platelet activator and aggregator, is not diminished with celecoxib administration due to selective COX-2 inhibition.  Consequently, there is greater potential for prothrombotic activity with celecoxib, which may lead to increased thrombotic cardiovascular events.  Therefore, celecoxib should be used cautiously in patients with cardiovascular disease or with risk factors for cardiovascular disease.  To minimize the risk of celecoxib-associated cardiovascular events, the lowest celecoxib dose for the shortest treatment duration should be utilized.  Celecoxib is FDA-approved for use to manage ankylosing spondylitis, juvenile rheumatoid arthritis, osteoarthritis, acute pain, primary dysmenorrhea, and rheumatoid arthritis.

Adults
The maximum recommended doses for celecoxib are listed in Table 1.  Dosages exceeding these recommendations will be reviewed.

Table 1 COX-2 Inhibitors - Adult Recommended Maximum Daily Dose
DRUG	MAXIMUM DAILY DOSE
Celecoxib (Celebrex®) (50 mg, 100 mg, 200 mg, 400 mg capsules)	acute pain (including primary dysmenorrhea): 400 mg ankylosing spondylitis:  400 mg osteoarthritis: 200 mg rheumatoid arthritis: 400 mg

      Pediatrics
Celecoxib is indicated for use in pediatric patients 2 years of age and older with a diagnosis of juvenile rheumatoid arthritis (JRA), now also known as juvenile idiopathic arthritis (JIA) or juvenile arthritis (JA).   However, celecoxib long-term cardiovascular toxicity as well as extended treatment for greater than six months has not been evaluated in pediatric patients.  Therefore, the lowest celecoxib dose for the shortest treatment duration should be employed.  Celecoxib safety and efficacy have not been determined in pediatric patients younger than 2 years of age. Recommended celecoxib pediatric dosages are summarized in Table 2.

Table 2 Recommended COX-2 Inhibitor Pediatric Daily Dosages
DRUG	MAXIMUM DAILY DOSE
Celecoxib	JRA (> 2 years of age):      10 kg to < 25 kg:               50 mg twice daily > 25 kg:                             100 mg twice daily

      Hepatic Impairment
In patients with moderate hepatic impairment (Child-Pugh Class B), the celecoxib dose should be reduced by 50%.  Celecoxib is not recommended for use in patients with severe hepatic impairment.

2.   Duration of Therapy

      Due to the potential for increased cardiovascular and gastrointestinal adverse events, celecoxib should be prescribed as the lowest effective dose for the shortest treatment duration that satisfies patient treatment goals.

a.   Therapy Limits

      1)   Celecoxib is prescribed on an as needed basis in the management of acute pain or dysmenorrhea.    
However, treatment regimens extending beyond a two week time period will be evaluated.

      2)   Celecoxib dosages used in osteoarthritis, rheumatoid arthritis, familial adenomatous polyposis, and   
ankylosing spondylitis may be chronically administered based on patient need.

      3).  Celecoxib safety and efficacy in pediatric patients 2 years of age and older with JRA for
            greater than a six-month treatment duration have not been established.  Patient profiles     
            containing prescriptions for JRA for greater than 6 months will be reviewed.

b.   COX-2 Inhibitor Use in Elderly Patients

            Elderly patients are frequently prescribed a COX-2 specific NSAID like celecoxib to manage acute and
chronic pain. Several issues surface with COX-2 inhibitor use in elderly patients, including potential
adverse effects and drug interactions.  NSAID-induced gastrointestinal toxicity is prevalent in the
elderly; therefore, COX-2 inhibitors like celecoxib or nonselective NSAIDs plus proton pump inhibitors
may offer safer alternatives to these patients.  Renal toxicity as well as adverse central nervous system
effects are more prevalent in elderly patients due to changes in metabolism, underlying disease states,
and concurrent drug therapy and should be considered prior to prescribing celecoxib, especially in higher
doses.  The potential for increased cardiovascular risk with COX-2 inhibitor use is also a factor when
evaluating NSAID therapy in elderly patients.  Elderly patients prescribed celecoxib, especially those at
higher risk, should be evaluated for appropriateness of therapy as well as potential for drug-drug
interactions.  Appropriate therapy duration and dosages should also be assessed.  Preventive measures
such as gastric antisecretory agents administered should be considered in some individuals to reduce GI
complications.  Medication profiles of elderly patients greater than 60 years of age prescribed celecoxib
in high doses or in patients with increased risk factors for adverse events or drug-drug interactions will
be reviewed.

       c.  Selective NSAID Use and Cardiovascular Risk
Some clinical trials have shown that patients prescribed selective and nonselective NSAIDs may be at increased risk for serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, all of which can be fatal.  Patients at greater risk are those with known CV disease or risk factors for CV disease.  Due to the lack of long-term clinical trial data, the Center for Drug Evaluation and Research has determined that the increased risk of CV events associated with NSAID use should be considered a class effect for both selective and nonselective NSAIDs until more results are available.   Patients should be prescribed the lowest effective NSAID dose for the shortest possible treatment duration to minimize the potential for cardiovascular adverse events.
NSAIDs may induce new onset hypertension or worsen pre-existing hypertension in some patients, which may contribute to the development of cardiovascular adverse events.  Blood pressure should be routinely monitored in patients prescribed NSAIDs.
NSAIDs may cause fluid retention or edema in some patients, and should be used cautiously in patients with a history of fluid retention or heart failure.

3.* Duplicative Therapy

The combined use of specific COX-2 inhibitors and nonspecific COX-1, COX-2 inhibitors does not provide additional therapeutic benefit and may result in additive adverse effects, including gastrointestinal toxicity. However, because celecoxib lacks antiplatelet effects, celecoxib may be used concurrently with low-dose aspirin prescribed for cardiovascular prophylaxis.  While an increased incidence of gastrointestinal adverse effects has been observed with combined celecoxib-aspirin therapy, the combination is cautiously warranted due to the potential cardiovascular benefits.  Concurrent therapy with celecoxib and nonspecific COX-1, COX-2 inhibitors other than low-dose aspirin is not recommended and will be reviewed.

4.* Drug-Drug Interactions

Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions.

Drug-drug interactions considered clinically significant for celecoxib are summarized in Table 3.  Only those drug-drug interactions classified as clinical significance level 1/contraindicated or those considered life-threatening which have not yet been classified will be reviewed:

REFERENCES

1. DRUGDEX® System (electronic version). Thomson Reuters (Healthcare) Inc., Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com.libproxy.uthscsa.edu.   Accessed January 6th, 2011.
2. Celecoxib (Celebrex®) Package Insert.  Pfizer Inc., January 2011.
3. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc; 2011. Available at: http://www.clinicalpharmacology.com. Accessed January 6th, 2011.
4. Drug Facts and Comparisons.  Clin-eguide [database online].  St. Louis, MO:  Wolters Kluwer Health, Inc; 2010.  Available at:  http://clineguide.com.  Accessed January 6th, 2011.
5. Drug interaction facts.  Clin-eguide [database online].  St. Louis, MO:  Wolters Kluwer Health, Inc; 2010.  Available at:  http://clineguide.com.  Accessed January 6th, 2011.
6. DRUG-REAX® System (electronic version). Thomson Reuters (Healthcare) Inc., Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com.libproxy.uthscsa.edu.  Accessed January 6th, 2011.
7. Mersfelder TL, Stewart LR.  Warfarin and celecoxib interaction.  Ann Pharmacother. 2000;34:325-7.
8. FitzGerald GA, Patrono C.  The coxibs, selective inhibitors of cyclooxygenase-2.  N Engl J Med. 2001;345:433-42.
9. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. The CLASS study: a randomized trial. JAMA. 2000;284;1247—55.
10. U.S. Food and Drug Administration.  Center for Drug Evaluation and Research.  COX-2 selective (includes Bextra, Celebrex, and Vioxx) and non-selective non-steroidal anti-inflammatory drugs (NSAIDs).  (July 18th, 2005)  Available at:  http://www.fda.gov/cder/drug/infopage/COX2/default.htm.
11. Bell GM, Schnitzer TJ.  COX-2 inhibitors and other nonsteroidal anti-inflammatory drugs in the treatment of pain in the elderly.  Clin Geriatr Med. 2001;17:489-502. 
12. Sowers JR, White WB, Pitt B, et al.  The effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus.  Arch Intern Med. 2005;165:161-8.
13. Solomon SD, McMurray JJ, Pfeffer MA, et al.  Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention.  N Engl J Med. 2005;352:1071-80.
14. Shaya FT, Blume SW, Blanchette CM, et al.  Selective cyclooxygenase-2 inhibition and cardiovascular effects:  An observational study of a Medicaid population.  Arch Intern Med. 2005;165:181-6.
15. Savage R.  Cyclo-oxygenase-2 inhibitors:  when should they be used in the elderly?  Drugs Aging. 2005;22:185-200.
16. Joshi GP, Gertler R, Fricker R.  Cardiovascular thromboembolic adverse effects associated with cyclooxygenase-2 selective inhibitors and nonselective antiinflammatory drugs.  Anesth Analg. 2007;105:1793–804.
17. Strand V.  Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin? Lancet. 2007;370(9605):2138-51.
18. McGettigan P, Henry D.  Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2.  JAMA.  2006;296(13):1633-44.
19.  Lehman TJA.  Classification of juvenile arthritis ((JRA/JIA).  In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2011.

 

Prepared by:  Drug Information Service, The University of Texas Health Science Center at San Antonio, and the College of Pharmacy, The University of Texas at Austin.