General

Genetic Implications:

Pronunciation:
sel-e-kox-ib

Trade Name(s)

• CeleBREX
• Elyxyb

Ther. Class.

antirheumatics

Pharm. Class.

cox 2 inhibitors

Indications

• Osteoarthritis.
• Rheumatoid arthritis.
• Ankylosing spondylitis.
• Juvenile rheumatoid arthritis.
• Acute pain.
• Primary dysmenorrhea.
• Acute treatment of migraine (with or without aura) (oral solution only).

Action

• Inhibits the enzyme COX-2. This enzyme is required for the synthesis of prostaglandins.
• Has analgesic, anti-inflammatory, and antipyretic properties.

Therapeutic Effect(s):

• Decreased pain and inflammation caused by osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, or juvenile rheumatoid arthritis.
• Decreased acute pain.

Pharmacokinetics

Absorption: Bioavailability unknown.

Distribution: Extensively distributed to tissues.

Protein Binding: 97%.

Metabolism and Excretion: Mostly metabolized by the liver via the CYP2C9 isoenzyme;  the CYP2C9 isoenzyme exhibits genetic polymorphism; poor metabolizers may have significantly ↑ celecoxib concentrations and an ↑ risk of adverse effects; <3% excreted unchanged in urine and feces.

Half-life: 11 hr.

TIME/ACTION PROFILE (pain reduction)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Cross-sensitivity may exist with other NSAIDs, including aspirin;
• History of allergic-type reactions to sulfonamides;
• History of allergic-type reactions to aspirin or other NSAIDs, including the aspirin triad (asthma, nasal polyps, and severe hypersensitivity reactions to aspirin);
• Advanced renal disease;
• Severe hepatic impairment;
• Coronary artery bypass graft (CABG) surgery;
• HF;
• OB:  Avoid use after 30 wk gestation.

Use Cautiously in:

• Cardiovascular disease or risk factors for cardiovascular disease (may ↑ risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, especially with prolonged use or use of higher doses); avoid use in patients with recent MI or HF;
• Renal impairment, hepatic impairment, dehydration, or concurrent diuretic, ACE inhibitor, or angiotensin receptor blocker therapy (↑ risk of renal impairment);
• History of long duration of NSAID use, smoking, alcohol use, advanced liver disease, coagulopathy, and poor general health (↑ risk of GI bleeding);
• Hypertension or fluid retention;
• Asthma;
•  Patients who are known or suspected to be poor CYP2C9 metabolizers (↓ initial dose by 50%; in patients with juvenile rheumatoid arthritis, use alternative treatment);
• Asthma;
• OB:  Use at or after 20 wk gestation may cause fetal or neonatal renal impairment; if treatment is necessary between 20 wk and 30 wk gestation, limit use to the lowest effective dose and shortest duration possible;
• Pedi:  Safety not established in children <2 yr or for longer than 6 mo;
• Geri:  ↑ risk of GI bleeding and renal impairment in older adults.

Exercise Extreme Caution in:

History of peptic ulcer disease or GI bleeding.

Adverse Reactions/Side Effects

CV: edema, HF, hypertension, MI, THROMBOSIS

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), EXFOLIATIVE DERMATITIS, rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS

F and E: hyperkalemia

GI: abdominal pain, diarrhea, dyspepsia, flatulence, GI BLEEDING, nausea

GU: renal impairment

Hemat: anemia

Neuro: dizziness, headache, insomnia, STROKE

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  CYP2C9 inhibitors  may ↑ levels and risk of toxicity.
• May ↓ effectiveness of  ACE inhibitors,  thiazide diuretics, and  furosemide.
•  Fluconazole  ↑ levels (use lowest recommended dosage).
• ↑ risk of GI bleeding with  anticoagulants,  aspirin,  clopidogrel,  ticagrelor,  prasugrel,  corticosteroids,  fibrinolytics,  SNRIs, or  SSRIs.
• May ↑ levels and risk of toxicity of  lithium  and  methotrexate.
• May ↑ risk of nephrotoxicity associated with  cyclosporine.
• May ↑ risk of myelosuppression, and renal and GI toxicity associated with  pemetrexed.

Route/Dosage

Osteoarthritis

PO (Adults): 200 mg once daily  or  100 mg twice daily.  CYP2C9 poor metabolizers:  ↓ dose by 50%.

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment:  ↓ dose by 50%.

Rheumatoid Arthritis

PO (Adults): 100–200 mg twice daily (capsules).  CYP2C9 poor metabolizers:  ↓ dose by 50%.

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment:  ↓ dose by 50%.

Ankylosing Spondylitis

PO (Adults): 200 mg once daily (capsules)  or  100 mg twice daily (capsules); may ↑ dose after 6 wk to 400 mg/day.  CYP2C9 poor metabolizers:  ↓ dose by 50%.

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment:  ↓ dose by 50%.

Juvenile Rheumatoid Arthritis

PO (Children ≥2 yr, 10–25 kg): 50 mg twice daily (capsules).

PO (Children ≥2 yr, ≥25 kg): 100 mg twice daily (capsules).

Hepatic Impairment 
PO (Children ≥2 yr): Moderate hepatic impairment:  ↓ dose by 50%.

Acute Pain or Primary Dysmenorrhea

PO (Adults): 400 mg initially, then a 200-mg dose if needed on the first day; then 200 mg twice daily as needed (capsules).  CYP2C9 poor metabolizers:  ↓ dose by 50%.

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment:  ↓ dose by 50%.

Acute Treatment of Migraine

PO (Adults): 120 mg as a single dose (not to exceed 120 mg/24 hr).  CYP2C9 poor metabolizers:  60 mg as a single dose (not to exceed 60 mg/24 hr).

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment:  60 mg as a single dose (not to exceed 60 mg/24 hr).

Availability (generic available)

Capsules: 50 mg, 100 mg, 200 mg, 400 mg

Oral solution: 25 mg/mL

Assessment

• Assess range of motion, degree of swelling, and pain in affected joints before and periodically during therapy.
• Assess patient for allergy to sulfonamides, aspirin, or NSAIDs. Patients with these allergies should not receive celecoxib.
• Assess patient for skin rash frequently during therapy. Discontinue at first sign of rash; may be life-threatening. SJS may develop. Treat symptomatically; may recur once treatment is stopped.
• Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, facial swelling) periodically during therapy. Discontinue therapy if symptoms occur.
•  Migraines: Assess intensity and frequency of migraine pain.

Lab Test Considerations:

May cause ↑ AST and ALT levels.

• May cause hypophosphatemia, hyperkalemia, and ↑ BUN.

Implementation

• Do not confuse Celebrex with Celexa or Cerebyx.
• Use lowest effective dose for shortest period of time.
• PO May be administered without regard to meals. Capsules may be opened and sprinkled on applesauce and ingested immediately with water. Mixture may be stored in the refrigerator for up to 6 hr.
  • Solution is clear and colorless.
• Limit  Elyxyb  use to ≤10 days per month to avoid medication-overuse headache.

Patient/Family Teaching

• Instruct patient to take celecoxib as directed. Do not take more than prescribed dose. Increasing doses does not appear to increase effectiveness. Advise patient to read  Medication Guide  before starting therapy and with each Rx refill in case of changes.
• Caution patient to avoid use of more than one NSAID or aspirin at a time; increases risk of GI toxicity. Increasing dose or adding an NSAID or aspirin does not provide increased pain relief but may increase incidence of side effects.
• Advise patient to notify health care professional promptly if signs or symptoms of GI toxicity (abdominal pain, black stools), skin rash, unexplained weight gain, or edema occurs. Patients should discontinue celecoxib and notify health care professional if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.
• May cause hypertension. Instruct patient in correct technique for monitoring BP and to notify health care professional if significant changes occur.
• Inform patient of increased risk of MI and stroke. Use lowest effective dose for shortest time. Advise patient to notify health care professional immediately if signs and symptoms (shortness of breath or trouble breathing, chest pain, weakness in one part or side of body, slurred speech, swelling of the face or throat) occur.
• Rep:  May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise women to avoid celecoxib in the 3rd trimester of pregnancy (after 29 wk), may cause premature closure of the fetal ductus arteriosus. Use of celecoxib after 20 wk may cause fetal renal dysfunction leading to oligohydramnios. May cause reversible infertility in women attempting to conceive; may consider discontinuing celecoxib.

Evaluation/Desired Outcomes

• Reduction in joint pain in patients with osteoarthritis.
• Reduction in joint tenderness, pain, and joint swelling in patients with rheumatoid arthritis, juvenile rheumatoid arthritis, and ankylosing spondylitis.
• Decreased pain.
• Decreased pain with dysmenorrhea.
• Decrease in acute migraine pain.