Celecoxib

Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that is used to treat arthritis, pain, menstrual cramps, and colonic polyps. Prostaglandins are chemicals that are important contributors to the inflammation of arthritis that causes pain, fever, swelling and tenderness. Celecoxib blocks the enzyme that makes prostaglandins (cyclooxygenase 2), resulting in lower concentrations of prostaglandins. As a consequence, inflammation and its accompanying pain, fever, swelling and tenderness are reduced. Celecoxib differs from other NSAIDs in that it causes less inflammation and ulceration of the stomach and intestine (at least with short-term use) and does not interfere with the clotting of blood.

NSAIDs have been found to prevent the formation and reduce the size of polyps in patients with the genetic disease, familial adenomatous polyposis (FAP). In FAP, patients develop large numbers of polyps in their colons, and the polyps invariably become malignant. The only cure of FAP is removal of the entire colon. Celecoxib is approved as an adjunctive (secondary) treatment among patients with FAP. The cramping and pain during menstrual periods is due to prostaglandins, and blocking the production of prostaglandins with celecoxib reduces the cramps and pain. The FDA approved celecoxib in December 1998.

Pregnancy category: C; D at ≥30 weeks' gestation (may cause premature closure of ductus arteriosus)

Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in ~7.5% of cases of spontaneous abortions and in ~2.6% of controls

Lactation: Drug enters breast milk; use caution

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.
 
This medication falls into category C, then category D from 30 weeks of gestation onward. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child. In addition, use of celecoxib during the third trimester of pregnancy should be avoided.

If you take too much celecoxib call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If celecoxib is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Your pharmacist can provide more information about celecoxib.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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NSAIA1 2 3 4 5 8 11 41 that is a selective inhibitor of cyclooxygenase-2 (COX-2);1 2 8 diaryl-substituted pyrazole derivative containing a sulfonamide substituent.1 2 3 4 5 8 11 41

Absorption

Bioavailability

Well absorbed following oral administration; peak plasma concentration usually attained within 3 hours in fasting individuals.1 2 23

Onset

Single doses provide pain relief within 60 minutes.1

Food

Bioavailability increased 10–20% and time to reach peak plasma concentration delayed 1–2 hours when 200-mg capsule is administered with a high-fat meal.1 2 Administration of dosages of 400 mg twice daily with food improves absorption.1

Administration as mixture in applesauce does not alter AUC, peak plasma concentration, or time to peak plasma concentration.1

Special Populations

In geriatric patients, peak plasma concentration and AUC increased by 40 and 50%, respectively.1 2

In patients with mild or moderate hepatic impairment, AUC increased by 40 or 180%, respectively.1 2

In patients with chronic renal impairment (GFR 35–60 mL/minute), AUC decreased by 40%; pharmacokinetics not studied in patients with severe renal impairment.1 2

Distribution

Extent

Not well characterized.1

Plasma Protein Binding

97% (principally albumin; α1-acid glycoprotein to a lesser extent).1 2 23

Elimination

Metabolism

Metabolized in the liver to inactive metabolites, mainly by CYP2C9.1 2 23

Elimination Route

Excreted in urine and feces principally as metabolites.1 2 23

Pediatric patients: Oral clearance increases in less-than-proportional manner with increasing weight; clearance predicted to be 40 or 24% lower in pediatric patients weighing 10 or 25 kg, respectively, than in a 70-kg adult.1

Half-life

11 hours under fasting conditions.1

It is very important that your doctor check the progress of you or your child at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood and urine tests may be needed to check for unwanted effects.

celecoxib may raise your risk of having a heart attack or stroke. This is more likely in people who already have heart disease. People who use celecoxib for a long time might also have a higher risk.

celecoxib may cause bleeding in your stomach or intestines. These problems can happen without warning signs. This is more likely if you or your child have had a stomach ulcer in the past, if you smoke or drink alcohol regularly, are over 60 years of age, are in poor health, or using certain other medicines (such as steroids or a blood thinner).

Using this medication in certain patients under the age of 18 for the treatment of juvenile rheumatoid arthritis may increase the risk of disseminated intravascular coagulation (bleeding problem). Talk with your doctor if you have concerns about this .

Serious skin reactions can occur with celecoxib. Stop using celecoxib and check with your doctor right away if you or your child have any of the following symptoms while taking celecoxib: blistering, peeling, or loosening of the skin; chills; cough; diarrhea; fever; itching; joint or muscle pain; red skin lesions; sore throat; sores, ulcers, white spots in the mouth or on the lips; or unusual tiredness or weakness.

Taking two or more of the nonsteroidal anti-inflammatory drugs (NSAIDs) together on a regular basis may increase the chance of unwanted effects. Also, taking acetaminophen, aspirin or other salicylates, or ketorolac (e.g., Toradol) regularly while you are taking a nonsteroidal anti-inflammatory drug may increase the chance of unwanted effects. The risk will depend on how much of each medicine you take every day, and on how long you take the medicines together. If your doctor tells you to take these medicines together on a regular basis, follow his or her directions carefully. However, do not take acetaminophen or aspirin or other salicylates together with celecoxib for more than a few days, and do not take any ketorolac (e.g., Toradol) while you are taking celecoxib, unless your doctor has directed you to do so and is following your progress.

Some possible warning signs of serious side effects that can occur during treatment with celecoxib may include black, tarry stools; decreased urination; severe stomach pain; skin rash; swelling of the face, fingers, feet, or lower legs; unusual bleeding or bruising; unusual weight gain; vomiting of blood or material that looks like coffee grounds; or yellow eyes and skin. Also, signs of serious heart problems could occur such as chest pain, tightness in the chest, fast or irregular heartbeat, or unusual flushing or warmth of the skin. Stop taking celecoxib and check with your doctor immediately if you notice any of these warning signs.

Celecoxib may cause a serious type of allergic reaction called anaphylaxis. Although this is rare, it may occur more often in patients who are allergic to aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), or sulfonamide-type drugs. Anaphylaxis can be life-threatening and requires immediate medical attention. The most serious signs of this reaction are very fast or irregular breathing, gasping for breath, wheezing, or fainting. Other signs may include changes in color of the skin of the face; very fast but irregular heartbeat or pulse; hive-like swellings on the skin; and puffiness or swellings of the eyelids or around the eyes. If these effects occur, get emergency help at once. Ask someone to drive you to the nearest hospital emergency room. If this is not possible, do not try to drive yourself. Call an ambulance, lie down, cover yourself to keep warm, and prop your feet higher than your head. Stay in that position until help arrives.

Using celecoxib during the later part of pregnancy can harm your unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away.

Tell your doctor if you or your child have unexplained weight gain or edema (fluid retention or body swelling) with celecoxib.

Before having any kind of surgery or medical tests, tell your doctor that you are taking celecoxib. It may be necessary for you to stop treatment for a while, or to change to a different nonsteroidal anti-inflammatory drug before your procedure.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

• It is used to ease pain and swelling.
• It is used to treat arthritis.
• It is used to ease painful period (menstrual) cycles.
• It is used to treat ankylosing spondylitis.
• It may be given to you for other reasons. Talk with the doctor.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• CeleBREX

Cmax is 40% higher and AUC is 50% higher.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Birth defects have been observed following in utero NSAID exposure in some studies, however data is 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. In addition, non-closure of the ductus arteriosus postnatally may occur and be resistant to medical management (Bermas 2014; Bloor 2013). 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.

Use of NSAIDs can be considered for the treatment of mild rheumatoid arthritis flares in pregnant women, however use should be minimized or avoided early and late in pregnancy (Bermas 2014; Saavedra Salinas 2015). Some guidelines recommend avoiding use of selective Cox-2 inhibitors completely during pregnancy due to limited data (Flint 2016).

The chronic use of NSAIDs in women of reproductive age may be associated with infertility that is reversible upon discontinuation of the medication. Consider discontinuing use in women having difficulty conceiving or those undergoing investigation of fertility. The use of NSAIDs close to conception may be associated with an increased risk of miscarriage (Bermas 2014; Bloor 2013).

Usual Adult Dose for Pain:

Acute pain: 400 mg initially, followed by 200 mg if needed on the first day. Then, 200 mg twice daily as needed.

Usual Adult Dose for Dysmenorrhea:

400 mg initially, followed by 200 mg if needed on the first day. Then, 200 mg twice daily as needed.

Usual Adult Dose for Osteoarthritis:

200 mg orally once daily or 100 mg orally twice daily.

Usual Adult Dose for Rheumatoid Arthritis:

100 to 200 mg orally twice daily.

Usual Adult Dose for Familial Adenomatous Polyposis:

400 mg orally twice daily with food.

Usual Adult Dose for Ankylosing Spondylitis:

200 mg orally once daily or 100 mg orally twice daily. If after 6 weeks of therapy no results are observed, a trial dose of 400 mg orally daily may be worthwhile. If no response is seen after 6 weeks, consideration should be given to alternate treatment options.

Usual Pediatric Dose for Juvenile Rheumatoid Arthritis:

2 years or older:

10 to less than or equal to 25 kg: 50 mg orally twice daily

Greater than 25 kg: 100 mg orally twice daily

Applies to celecoxib: oral capsule

Along with its needed effects, celecoxib may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking celecoxib:

• Cough
• fever
• skin rash
• sneezing
• sore throat
• swelling of the face, fingers, feet, or lower legs

• Abnormal growth in the breast
• arm, back, or jaw pain
• bloody or black, tarry stools
• blurred vision
• burning feeling in the chest or stomach
• burning or stinging of the skin
• burning, tingling, numbness, or pain in the hands, arms, feet, or legs
• chest pain or discomfort
• chest tightness or heaviness
• chills
• confusion
• congestion in the chest
• cramps
• diarrhea
• dry mouth
• earache
• fast or irregular heartbeat
• heartburn
• heavy bleeding
• heavy non-menstrual vaginal bleeding
• high blood pressure
• increased hunger
• increased thirst
• increased urination
• loss of appetite
• loss of consciousness
• muscle aches and pains
• nausea
• nerve pain
• painful blisters on the trunk of body
• painful cold sores or blisters on the lips, nose, eyes, or genitals
• pale skin
• redness or swelling in the ear
• sensation of pins and needles
• soreness or redness around the fingernails and toenails
• stabbing pain
• stiff neck
• stomachache
• stomach pain (severe)
• sweating
• tenderness in the stomach area
• troubled breathing with exertion
• unexplained weight loss
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain
• vomiting
• vomiting of blood or material that looks like coffee grounds
• weakness
• wheezing

• Area rash
• changes in skin color
• clay-colored stools
• dilated neck veins
• light-colored stools
• pale or a bluish color skin of the fingers or toes
• seizures
• slurred speech
• sores, welting, or blisters
• sudden and severe inability to speak
• unpleasant breath odor
• weakness in the arm or leg on one side of the body
• yellow eyes and skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking celecoxib:

• Continuing thirst
• dizziness
• drowsiness
• headache, severe or continuing
• shortness of breath
• sudden decrease in the amount of urine
• troubled breathing
• weight gain

Some side effects of celecoxib may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Back pain
• gas
• headache
• heartburn
• inability to sleep
• pain or burning in the throat
• stuffy or runny nose

• Anxiety
• bleeding after defecation
• bloody or cloudy urine
• breast pain
• bone deformity
• buzzing or ringing noise in the ears
• change in sense of taste
• constipation
• decrease in height
• decreased appetite
• depression
• difficult, burning, or painful urination
• difficulty with moving or walking
• difficulty with swallowing
• excessive muscle tone, muscle tension, or tightness
• excessive tearing
• feeling of pressure
• hair loss
• hives
• hoarseness
• increased sweating
• infection
• inflammation
• itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at site
• itching of the vagina or genital area
• joint or muscle pain or stiffness
• large, flat, blue, or purplish patches in the skin
• loss of energy or weakness
• loss of hearing
• muscle pain increased
• muscle stiffness
• nervousness
• numbness or tingling in the fingers or toes
• pain during sexual intercourse
• pain in the back, ribs, arms, or legs
• pounding heartbeat
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• redness or swelling in the arms or legs
• sensitivity of the skin to sunlight
• severe sunburn
• sleepiness
• straining while passing stool
• sudden sweating and feelings of warmth
• swelling
• swelling or inflammation of the mouth
• tenderness
• thick, white vaginal discharge with no odor or with a mild odor
• thinning of the hair
• trouble with swallowing
• troubled breathing
• uncomfortable swelling around anus
• unexplained weight loss
• voice changes
• warmth on the skin
• weakness or heaviness of the legs

• Bleeding gums
• blistering, peeling, or loosening of the skin
• bloating
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of sense of smell
• pain
• pinpoint red spots on the skin
• red or irritated eyes
• red skin lesions, often with a purple center
• shakiness and unsteady walk
• sores, ulcers, or white spots in the mouth or on the lips
• stomach cramps
• swelling of the neck
• tenderness
• trembling, or other problems with muscle control or coordination
• unsteadiness
• watery or bloody diarrhea

Day 1: 400 mg orally once followed by an additional 200 mg orally if needed
Usual dose: 200 mg orally twice a day as needed

Comment: The lowest effective dose for the shortest duration consistent with individual patient treatment goals should be used.

Use: For the management of acute pain.

Usual dose: 200 mg orally once a day OR 100 mg orally twice a day

Comment: Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

Use: For the relief of the signs and symptoms of osteoarthritis.

Age: 2 years or older:

Weight: 10 kg to 25 kg: 50 mg orally twice a day
Weight: Greater than 25 kg: 100 mg orally twice a day

Comments:
-The lowest effective dose for the shortest duration consistent with individual patient treatment goals should be used.
-For pediatric patients who are poor metabolizers of CYP450 2C9, consider alternative treatment.

Use: For the relief of the signs and symptoms of juvenile rheumatoid arthritis in patients 2 years or older.

US BOXED WARNINGS: CARDIOVASCULAR AND GASTROINTESTINAL RISKS
-Cardiovascular Risk: This drug may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs may have a similar risk. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. This drug is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
-Gastrointestinal Risk: NSAIDs, including this drug, cause an increased risk of serious gastrointestinal 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 are at greater risk for serious gastrointestinal events.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Since celecoxib is sometimes used when needed, you may not be on a dosing schedule. If you are on a schedule, use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.