What Pain Reliever Can I Take With Celebrex?

What Pain Reliever Can I Take With Celebrex
Taking celecoxib with other pain medicines – Don’t take other anti-inflammatory medicines such as diclofenac, ibuprofen or naproxen while taking celecoxib. This can increase your risk of side effects. It’s safe to take celecoxib with paracetamol because they work differently.

Contents

Is it okay to take Tylenol with Celebrex?

Yes, Celebrex is an anti-inflammatory medication; thus, it is OK to take with Tylenol.

Can I take Tylenol or ibuprofen with Celebrex?

Answer – Tylenol (generic Acetaminophen) is commonly used as an adjunct for pain relief in patients with various forms of musculoskeletal pain. While acetaminophen is not an anti-inflammatory agent (like NSAIDS, including Celebrex), it does act on pain pathways.

It is important for patients to inform their physicians of breakthrough pain that is requiring the use of any over-the-counter agents as there may need to be increased monitoring for certain possible side effects (increased liver function tests, etc). It is also important to remember that combining different NSAIDS is not recommended, including over-the-counter agents such as ibuprofen (Advil, Motrin, etc) or naproxen (Alleve) with prescription NSAIDS (Celebrex, diclofenac, and many others).

: Combining NSAIDS and Tylenol for pain • Johns Hopkins Arthritis Center

What drugs should not be taken with Celebrex?

Interactions – may change how your work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and,

  1. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.
  2. Some products that may interact with this drug include:, (such as, ), angiotensin II receptor blockers (such as, ),,, “” ( such as ).
  3. This may increase the risk of bleeding when taken with other drugs that also may cause bleeding.

Examples include anti- drugs such as, “” such as //, among others. Check all prescription and nonprescription medicine labels carefully since many medications contain pain relievers/fever reducers (, such as or ). These drugs are similar to and may increase your risk of side effects if taken together.

Can I take Celebrex and ibuprofen together?

Interactions between your drugs – Using celecoxib together with ibuprofen may increase side effects associated with these medications. In particular, there may be an increased risk of serious gastrointestinal toxicity including inflammation, bleeding, ulceration, and perforation.

The risk is dependent on both dosage and duration of therapy of each medication. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications.

It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor. Switch to professional interaction data

How long does it take for Celebrex to kick in for pain?

By blocking COX-2, celecoxib reduces inflammation in the body and pain. How long will it take to work? Some people will notice the effects of celecoxib within the first few hours of taking a dose. For others, the effects may not be evident for days and even up to a week or two after the medicine has been started.

Can Aleve be taken with Celebrex?

Interactions between your drugs – Using celecoxib together with naproxen may increase side effects associated with these medications. In particular, there may be an increased risk of serious gastrointestinal toxicity including inflammation, bleeding, ulceration, and perforation.

  • The risk is dependent on both dosage and duration of therapy of each medication.
  • Talk to your doctor if you have any questions or concerns.
  • Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications.

It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor. Switch to professional interaction data

How long should you take Celebrex for inflammation?

How much to take – Osteoarthritis 200 mg once daily or 100 mg twice daily. Rheumatoid arthritis 100 mg twice daily. Your doctor may increase the dose to 200 mg twice a day for a short period of time if you have a flare up. Ankylosing spondylitis 100 mg twice daily or 200 mg once daily.

Is Celebrex stronger than ibuprofen 800?

Results swing both ways: Celebrex was more effective for pain from ankle sprain, ibuprofen was more effective for dental pain, and both were equally effective for pain from knee osteoarthritis. It’s a draw, though it depends on what type of pain you have.

Is Celebrex an anti-inflammatory or a painkiller?

Descriptions – Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) used to treat mild to moderate pain and help relieve symptoms of arthritis (eg, osteoarthritis, rheumatoid arthritis, or juvenile rheumatoid arthritis), such as inflammation, swelling, stiffness, and joint pain.

However, this medicine does not cure arthritis and will help you only as long as you continue to take it. Celecoxib is also used to treat ankylosing spondylitis, which is a type of arthritis that affects the joints in the spine. This medicine may also be used to treat acute pain and menstrual cramps. Celecoxib is also used to treat acute migraine headaches with or without aura.

However, this medicine is not used to prevent migraines. This medicine is available only with your doctor’s prescription. This product is available in the following dosage forms:

  • Capsule
  • Solution

Why can’t you lay down for 10 minutes after taking Celebrex?

Medicines and the Digestive System Medicines taken by mouth can affect the digestive system in a number of different ways. Both prescription and over-the-counter medicines, while usually safe and effective, may create harmful effects in some people. Certain medicines taken together may interact and cause harmful side effects.

In addition, it is important that your healthcare providers know about any allergies, sensitivities, as well as other medical conditions you have before taking a new medicine. People with food intolerance, such as gluten intolerance, must be sure medicines do not contain fillers or additives with these substances.

Listed below are some problems related to the digestive system that can happen when taking medicine:

Irritation of the esophagus Tips to prevent irritation of the esophagus
Some people have difficulty swallowing tablets or capsules, or sometimes take medicines without liquid. Tablets or capsules that stay in the esophagus may release chemicals that can irritate the lining of the esophagus. This may cause ulcers, bleeding, perforation, and narrowing (strictures) of the esophagus. The risk of these types of injuries is greater in persons with medical conditions involving the esophagus, including the following:

Strictures (narrowing of the esophagus) Scleroderma (hardening of the skin) Achalasia (irregular muscle activity of the esophagus, which delays passage of food) Stroke

Certain medicines can also cause ulcers in the esophagus when they become lodged there. These include aspirin, certain antibiotics, quinidine, potassium chloride, vitamin C, and iron.

Stand or sit when swallowing medicines. Take several swallows of liquid before taking the medicine, and swallow the medicine with a full 8 oz. glass of liquid. Do not lie down immediately after taking medicine, to make sure the pills have gone through the esophagus into the stomach. Notify your healthcare provider if you experience painful swallowing or feel that the medicine is sticking in your throat.

About esophageal reflux Tips to avoid reflux
Some medicines interfere with the action of the sphincter muscle, located between the esophagus and stomach. This muscle allows the passage of food into the stomach after swallowing. This can increase the chances of reflux, or backup of the stomach’s acidic contents into the esophagus. Classes of medicines that may increase the severity of reflux include the following:

ul> Nonsteroidal anti-inflammatory agents (NSAIDs) Nitrates Theophylline Calcium channel blockers Oral antibiotics Birth control pills

Avoid coffee, alcohol, chocolate, and fatty or fried foods, which may worsen reflux. Quit, or reduce, smoking. Do not lie down right after eating.

Irritation of the stomach Tips to prevent irritation of the stomach One of the most common irritants to the lining of the stomach is that caused by nonsteroidal anti-inflammatory drugs (NSAIDs). This includes medicines, such as ibuprofen and other common pain relievers.

These medicines weaken the ability of the lining to resist acid made in the stomach and can sometimes lead to inflammation of the stomach lining (gastritis), ulcers, bleeding, or perforation of the lining.Older people are at greater risk for irritation from these medicines because they are more likely to take these pain relievers for chronic conditions.

People with a history of peptic ulcers and gastritis are also at risk.

Take coated tablets, which may reduce irritation. Do not drink alcoholic beverages when taking these medicines. Take medicines with food, or with a full glass of milk or water, which may reduce irritation.

Constipation Tips to prevent constipation A variety of medicines can cause constipation. This happens because these medicines affect the nerve and muscle activity in the colon (large intestine), resulting in the slow and difficult passage of stool.Medicines that may cause constipation include the following:

Antihypertensives Anticholinergics Cholestyramine Iron Antacids containing mostly aluminum Narcotics/pain medicines

Eat a well-balanced diet including fruits, vegetables, and whole grains. Drink plenty of fluids. Exercise regularly. Discuss taking a laxative or stool softener with your healthcare provider.

Diarrhea Tips to prevent diarrhea Diarrhea is most often caused by antibiotics, which affect bacteria normally present in the large intestine. These changes in intestinal bacteria allow the overgrowth of the bacteria Clostridium difficile (C. difficile), which causes a more serious antibiotic-induced diarrhea.

Penicillin, including ampicillin and amoxicillin Clindamycin Cephalosporins

This colitis is usually treated with another antibiotic that acts on the C. difficile. Certain medicines may also alter the movements or fluid content of the colon without causing colitis. Colchicine and magnesium-containing antacids can both cause diarrhea.Talk with your healthcare provider if the diarrhea persists for several days.

Usually, preventing diarrhea involves avoiding foods known to irritate your stomach. Treatment usually involves replacing lost fluids, and may include antibiotics when bacterial infections are the cause. Eating foods that are high in lactose bacillus, such as yogurt, acidophilus milk/pills, or cottage cheese, helps to replenish the normal bacteria present in the large intestine.

: Medicines and the Digestive System

What organ is Celebrex hard on?

Kidney effects – Celecoxib, like the non-specific NSAIDs, can adversely affect kidney function. For this reason, people with abnormal kidney function should avoid or sharply limit the use of this medication, and if it is used the kidney function should be followed. Even in people with normal kidney function, if celecoxib is used long-term, then the kidney function should be periodically checked.

Does Celebrex cause weight gain?

Cardiovascular problems – Celebrex has a boxed warning for cardiovascular (heart and blood vessel) problems. A boxed warning is the most serious warning from the FDA. This warning alerts doctors and patients about drug effects that may be dangerous. Celebrex is a type of drug called a nonsteroidal anti-inflammatory drug (NSAID),

Taking an NSAID can increase your risk of cardiovascular problems, such as heart attack or stroke, In some cases, these problems can be fatal. You have a higher risk for cardiovascular problems if you take Celebrex at a high dose or for long periods of time. And if you have heart disease, you could be at a higher risk for cardiovascular problems with Celebrex.

(To learn more, see the ” Celebrex precautions ” section below.) You shouldn’t take Celebrex if you’re planning to have or recently had a coronary artery bypass graft (heart bypass surgery). This is a surgery to improve blood supply to your heart. Taking Celebrex to treat pain after heart bypass surgery can increase the risk of having a heart attack or stroke.

  • Talk with your doctor about what other pain relievers are suitable for you.
  • How often do cardiovascular problems occur with Celebrex? Clinical studies that were carried out before Celebrex was approved included people with and without a risk of cardiovascular problems.
  • They were being treated for OA or RA.

In these studies:

heart attack occurred in 0.1% to 1.9% of people who took Celebrexstroke occurred in less than 0.1% of people who took Celebrex

It’s not known how often these side effects occurred in people who took other drugs in these studies. And it’s not known how often heart attack and stroke occurred in people who took Celebrex for other conditions. One large clinical study assessed the risk for heart attack and stroke with Celebrex in people who already had a high risk of cardiovascular problems.

This study was carried out after Celebrex had been approved for prescribing. This study involved 24,081 people with OA or RA. They were split into three groups. One group took 100 milligrams (mg) of Celebrex twice a day. A second group took 375 to 500 mg of naproxen twice a day. The third group took 600 to 800 mg of ibuprofen three times a day.

Naproxen and ibuprofen are other types of NSAIDs. Over 30 months, heart attack, stroke, or death from cardiovascular disease occurred in:

2.3% of people who took Celebrex2.5% of people who took naproxen2.7% of people who took ibuprofen

What are the symptoms of cardiovascular problems? Symptoms of cardiovascular problems while taking Celebrex can include:

shortness of breath or trouble breathingpain, tightness, or pressure in your chestpain in your jaw, neck, back, or armsuddenly feeling dizzy or lightheaded weakness in one side of your bodydrooping of one side of your faceslurred speech

Call your doctor right away if you have any of these symptoms. Call 911 or your local emergency number if your symptoms feel life threatening or if you think you’re having a medical emergency. To minimize the risk of cardiovascular problems, Celebrex should be used at the lowest possible dose for the shortest possible time. Your doctor will recommend the best dosage for you.

Can Celebrex be used with Advil?

Interactions between your drugs – Using celecoxib together with ibuprofen may increase side effects associated with these medications. In particular, there may be an increased risk of serious gastrointestinal toxicity including inflammation, bleeding, ulceration, and perforation.

  • The risk is dependent on both dosage and duration of therapy of each medication.
  • Talk to your doctor if you have any questions or concerns.
  • Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications.

It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor. Switch to professional interaction data

Can I take an anti-inflammatory with Celebrex?

What to avoid – Avoid taking aspirin or other NSAIDs while you are taking Celebrex, unless your doctor tells you to. Avoid drinking alcohol. It may increase your risk of stomach bleeding. Ask a doctor or pharmacist before using other medicines for pain, fever, swelling, or cold/flu symptoms. They may contain ingredients similar to celecoxib (such as aspirin, ibuprofen, ketoprofen, or naproxen ).

When is the best time to take Celebrex?

pronounced as (sel” e kox’ ib) People who take nonsteroidal anti-inflammatory drugs (NSAIDs) (other than aspirin) such as celecoxib may have a higher risk of having a heart attack or a stroke than people who do not take these medications. These events may happen without warning and may cause death.

This risk may be higher for people who take NSAIDs for a long time. Do not take an NSAID such as celecoxib if you have recently had a heart attack, unless directed to do so by your doctor. Tell your doctor if you or anyone in your family has or has ever had heart disease, a heart attack, or a stroke, if you smoke, and if you have or have ever had high cholesterol, high blood pressure, or diabetes.

Get emergency medical help right away if you experience any of the following symptoms: chest pain, shortness of breath, weakness in one part or side of the body, or slurred speech. If you will be undergoing a coronary artery bypass graft (CABG; a type of heart surgery), you should not take celecoxib right before or right after the surgery.

  • NSAIDs such as celecoxib may cause ulcers, bleeding, or holes in the stomach or intestine.
  • These problems may develop at any time during treatment, may happen without warning symptoms, and may cause death.
  • The risk may be higher for people who take NSAIDs for a long time, are older in age, have poor health, or drink large amounts of alcohol while taking celecoxib.

Tell your doctor if you drink large amounts of alcohol or if you take any of the following medications: anticoagulants (‘blood thinners’) such as warfarin (Coumadin, Jantoven); aspirin; other NSAIDs such as ibuprofen (Advil, Motrin) or naproxen (Aleve, Naprosyn); oral steroids such as dexamethasone, methylprednisolone (Medrol), and prednisone (Rayos); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Paxil, Pexeva), and sertraline (Zoloft); or serotonin norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Pristiq), duloxetine (Cymbalta), and venlafaxine (Effexor XR).

  • Also tell your doctor if you have or have ever had ulcers or bleeding in your stomach or intestines or other bleeding disorders.
  • If you experience any of the following symptoms, stop taking celecoxib and call your doctor: stomach pain, heartburn, vomiting a substance that is bloody or looks like coffee grounds, blood in the stool, or black and tarry stools.

Keep all appointments with your doctor and the laboratory. Your doctor will monitor your symptoms carefully and will probably order certain tests to check your body’s response to celecoxib. Be sure to tell your doctor how you are feeling so that your doctor can prescribe the right amount of medication to treat your condition with the lowest risk of serious side effects.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with celecoxib and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website ( http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm ) or the manufacturer’s website to obtain the Medication Guide.

Celecoxib is used to relieve pain, tenderness, swelling and stiffness caused by osteoarthritis (arthritis caused by a breakdown of the lining of the joints), rheumatoid arthritis (arthritis caused by swelling of the lining of the joints), and ankylosing spondylitis (arthritis that mainly affects the spine).

  • Celecoxib is also used to treat juvenile rheumatoid arthritis (a type of arthritis that affects children) in children 2 years of age and older.
  • Celecoxib is also used to treat painful menstrual periods and to relieve other types of short-term pain including pain caused by injuries, surgery and other medical or dental procedures, or medical conditions that last for a limited time.

Celecoxib is in a class of NSAIDs called COX-2 inhibitors. It works by stopping the body’s production of a substance that causes pain and inflammation. Celecoxib comes as a capsule to take by mouth. Celecoxib capsules are usually taken once or twice a day.

If you are taking up to 200 mg of celecoxib capsules at a time, you may take the medication with or without food. If you are taking more than 200 mg of celecoxib capsules at a time, you should take the medication with food. Ask your doctor or pharmacist if you are not sure if you need to take your medication with food.

To help you remember to take celecoxib capsules, take it around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take celecoxib exactly as directed.

Do not take more or less of it or take it more often than prescribed by your doctor. If you cannot swallow the capsules or if you are giving this medication to a child, you may open the capsules and sprinkle the contents over a teaspoon of cold or room temperature applesauce. You may prepare the mixture in advance and store it for up to 6 hours in a refrigerator.

When you are ready to take your medication, swallow all of the mixture. Then drink water to wash down the mixture and be sure that you have swallowed all of it. Celecoxib is also sometimes used with surgery and other treatments to reduce the number of polyps (abnormal growths) in the colon (large intestine) and rectum in patients with familial adenomatous polyposis (a condition in which hundreds or thousands of polyps form in the colon and cancer may develop).

Does Celebrex make you tired or sleepy?

– Celecoxib oral capsule does not cause drowsiness, but it can cause other side effects.

Is 200mg of Celebrex a lot?

Celebrex 200 mg capsule This information is intended for use by health professionals Celebrex 200 mg hard capsules Each capsule contains 200 mg celecoxib. Excipient with known effect Lactose (each capsule contains 49.8 mg lactose monohydrate; see section 4.4).

For the full list of excipients, see section 6.1. Hard capsules (capsule). Opaque, white with two gold bands marked 7767 and 200. Celebrex is indicated in adults for the symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. The decision to prescribe a selective cyclooxygenase-2 (COX-2) inhibitor should be based on an assessment of the individual patient’s overall risks (see sections 4.3 and 4.4).

Posology As the cardiovascular (CV) risks of celecoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. The patient’s need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis (see sections 4.3, 4.4, 4.8 and 5.1).

Osteoarthritis The usual recommended daily dose is 200 mg taken once daily or in two divided doses. In some patients, with insufficient relief from symptoms, an increased dose of 200 mg twice daily may increase efficacy. In the absence of an increase in therapeutic benefit after two weeks, other therapeutic options should be considered.

Rheumatoid arthritis The initial recommended daily dose is 200 mg taken in two divided doses. The dose may, if needed, later be increased to 200 mg twice daily. In the absence of an increase in therapeutic benefit after two weeks, other therapeutic options should be considered.

  • The maximum recommended daily dose is 400 mg for all indications.
  • Special populations
  • Elderly

As in younger adults, 200 mg per day should be used initially. The dose may, if needed, later be increased to 200 mg twice daily. Particular caution should be exercised in elderly with a body weight less than 50 kg (see sections 4.4 and 5.2).

  1. Paediatric population
  2. Celecoxib is not indicated for use in children.
  3. CYP2C9 poor metabolisers

Patients who are known, or suspected to be CYP2C9 poor metabolisers based on genotyping or previous history/experience with other CYP2C9 substrates should be administered celecoxib with caution as the risk of dose-dependent adverse effects is increased.

Consider reducing the dose to half the lowest recommended dose (see section 5.2). Hepatic impairment Treatment should be initiated at half the recommended dose in patients with established moderate liver impairment with a serum albumin of 25-35 g/l. Experience in such patients is limited to cirrhotic patients (see sections 4.3, 4.4 and 5.2).

Renal impairment Experience with celecoxib in patients with mild or moderate renal impairment is limited, therefore such patients should be treated with caution (see sections 4.3, 4.4 and 5.2). Method of administration Oral use Celebrex may be taken with or without food.

For patients who have difficulty swallowing capsules, the contents of a celecoxib capsule can be added to applesauce, rice gruel, yogurt or mashed banana. To do so, the entire capsule contents must be carefully emptied onto a level teaspoon of cool or room temperature applesauce, rice gruel, yogurt or mashed banana and should be ingested immediately with 240 ml of water.

The sprinkled capsule contents on applesauce, rice gruel or yogurt are stable for up to 6 hours under refrigerated conditions (2-8 °C). The sprinkled capsule contents on mashed banana should not be stored under refrigerated conditions and should be ingested immediately.

  • Known hypersensitivity to sulfonamides.
  • Active peptic ulceration or gastrointestinal (GI) bleeding.
  • Patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid (aspirin) or other non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors.

In pregnancy and in women of childbearing potential unless using an effective method of contraception (see section 4.6). Celecoxib has been shown to cause malformations in the two animal species studied (see sections 4.6 and 5.3). The potential for human risk in pregnancy is unknown, but cannot be excluded. Breast-feeding (see sections 4.6 and 5.3).

  1. Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10).
  2. Patients with estimated creatinine clearance <30 ml/min.
  3. Inflammatory bowel disease.
  4. Congestive heart failure (NYHA II-IV).
  5. Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease.

Gastrointestinal (GI) effects Upper and lower gastrointestinal complications (perforations, ulcers or bleedings ), some of them resulting in fatal outcome, have occurred in patients treated with celecoxib. Caution is advised with treatment of patients most at risk of developing a gastrointestinal complication with NSAIDs; the elderly, patients using any other NSAID or antiplatelet drugs (such as acetylsalicylic acid), or glucocorticoids concomitantly, patients using alcohol, or patients with a prior history of gastrointestinal disease, such as ulceration and GI bleeding.

There is further increase in the risk of gastrointestinal adverse effects for celecoxib (gastrointestinal ulceration or other gastrointestinal complications), when celecoxib is taken concomitantly with acetylsalicylic acid (even at low doses). A significant difference in GI safety between selective COX-2 inhibitors + acetylsalicylic acid vs,

NSAIDs + acetylsalicylic acid has not been demonstrated in long-term clinical trials (see section 5.1).

  • Concomitant NSAID use
  • The concomitant use of celecoxib and a non-aspirin NSAID should be avoided.
  • Cardiovascular effects

Increased number of serious cardiovascular (CV) events, mainly myocardial infarction, has been found in a long-term placebo-controlled study in subjects with sporadic adenomatous polyps treated with celecoxib at doses of 200 mg bis in die (BID) and 400 mg BID compared to placebo (see section 5.1).

As the cardiovascular risks of celecoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. NSAIDs, including COX-2 selective inhibitors, have been associated with increased risk of cardiovascular and thrombotic adverse events when taken long-term.

The exact magnitude of the risk associated with a single-dose has not been determined, nor has the exact duration of therapy associated with increased risk. The patient’s need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis (see sections 4.2, 4.3, 4.8 and 5.1).

Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with celecoxib after careful consideration (see section 5.1). COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular thrombo-embolic diseases because of their lack of antiplatelet effects.

Therefore, antiplatelet therapies should not be discontinued (see section 5.1). Fluid retention and oedema As with other medicinal products known to inhibit prostaglandin synthesis, fluid retention and oedema have been observed in patients taking celecoxib.

Therefore, celecoxib should be used with caution in patients with history of cardiac failure, left ventricular dysfunction or hypertension, and in patients with pre-existing oedema from any other reason, since prostaglandin inhibition may result in deterioration of renal function and fluid retention.

Caution is also required in patients taking diuretic treatment or otherwise at risk of hypovolaemia. Hypertension As with all NSAIDS, celecoxib can lead to the onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of cardiovascular events.

Therefore, blood pressure should be monitored closely during the initiation of therapy with celecoxib and throughout the course of therapy. Hepatic and renal effects Compromised renal or hepatic function and especially cardiac dysfunction are more likely in the elderly and therefore medically appropriate supervision should be maintained.

NSAIDs, including celecoxib, may cause renal toxicity. Clinical trials with celecoxib have shown renal effects similar to those observed with comparator NSAIDs. Patients at greatest risk for renal toxicity are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, angiotensin converting enzyme (ACE)-inhibitors, angiotensin II receptor antagonists, and the elderly (see section 4.5).

  1. Such patients should be carefully monitored while receiving treatment with celecoxib.
  2. Some cases of severe hepatic reactions, including fulminant hepatitis (some with fatal outcome), liver necrosis and, hepatic failure (some with fatal outcome or requiring liver transplant), have been reported with celecoxib.

Among the cases that reported time to onset, most of the severe adverse hepatic events developed within one month after initiation of celecoxib treatment (see section 4.8). If during treatment, patients deteriorate in any of the organ system functions described above, appropriate measures should be taken and discontinuation of celecoxib therapy should be considered.

CYP2D6 inhibition Celecoxib inhibits CYP2D6. Although it is not a strong inhibitor of this enzyme, a dose reduction may be necessary for individually dose-titrated medicinal products that are metabolised by CYP2D6 (see section 4.5). CYP2C9 poor metabolisers Patients known to be CYP2C9 poor metabolisers should be treated with caution (see section 5.2).

Skin and systemic hypersensitivity reactions Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of celecoxib (see section 4.8).

  • Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment.
  • Serious hypersensitivity reactions (including anaphylaxis, angioedema and drug rash with eosinophilia and systemic symptoms (DRESS), or hypersensitivity syndrome), have been reported in patients receiving celecoxib (see section 4.8).

Patients with a history of sulfonamide allergy or any drug allergy may be at greater risk of serious skin reactions or hypersensitivity reactions (see section 4.3). Celecoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

  1. General
  2. Celecoxib may mask fever and other signs of inflammation.
  3. Use with oral anticoagulants

In patients on concurrent therapy with warfarin, serious bleeding events, some of them fatal, have been reported. Increased prothrombin time (INR) with concurrent therapy has been reported. Therefore, this should be closely monitored in patients receiving warfarin/coumarin-type oral anticoagulants, particularly when therapy with celecoxib is initiated or celecoxib dose is changed (see section 4.5). Concomitant use of anticoagulants with NSAIDS may increase the risk of bleeding. Caution should be exercised when combining celecoxib with warfarin or other oral anticoagulants, including novel anticoagulants (e.g. apixaban, dabigatran, and rivaroxaban). Excipients Celebrex 100 mg and 200 mg capsules contain lactose (149.7 mg and 49.8 mg, respectively). Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. Celebrex 100 mg and 200 mg contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’. Pharmacodynamic interactions Anticoagulants Anticoagulant activity should be monitored particularly in the first few days after initiating or changing the dose of celecoxib in patients receiving warfarin or other anticoagulants since these patients have an increased risk of bleeding complications. Therefore, patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with celecoxib is initiated or the dose of celecoxib is changed (see section 4.4). Bleeding events in association with increases in prothrombin time have been reported, predominantly in the elderly, in patients receiving celecoxib concurrently with warfarin, some of them fatal. Anti-hypertensives NSAIDs may reduce the effect of anti-hypertensive medicinal products including ACE-inhibitors, angiotensin II receptor antagonists, diuretics and beta-blockers. As for NSAIDs, the risk of acute renal insufficiency, which is usually reversible, may be increased in some patients with compromised renal function (e.g. dehydrated patients, patients on diuretics, or elderly patients) when ACE-inhibitors, angiotensin II receptor antagonists, and/or diuretics are combined with NSAIDs, including celecoxib (see section 4.4). Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter. In a 28-day clinical study in patients with lisinopril-controlled Stage I and II hypertension, administration of celecoxib 200 mg BID resulted in no clinically significant increases, when compared to placebo treatment, in mean daily systolic or diastolic blood pressure as determined using 24-hour ambulatory blood pressure monitoring. Among patients treated with celecoxib 200 mg BID, 48 % were considered unresponsive to lisinopril at the final clinic visit (defined as either cuff diastolic blood pressure >90 mmHg or cuff diastolic blood pressure increased >10 % compared to baseline), compared to 27 % of patients treated with placebo; this difference was statistically significant. Ciclosporin and tacrolimus Co-administration of NSAIDs and ciclosporin or tacrolimus may increase the nephrotoxic effect of ciclosporin or tacrolimus, respectively. Renal function should be monitored when celecoxib and any of these medicinal products are combined. Acetylsalicylic acid Celecoxib can be used with low-dose acetylsalicylic acid but is not a substitute for acetylsalicylic acid for CV prophylaxis. In the submitted studies, as with other NSAIDs, an increased risk of gastrointestinal ulceration or other gastrointestinal complications compared to use of celecoxib alone was shown for concomitant administration of low-dose acetylsalicylic acid (see section 5.1).

  • Pharmacokinetic interactions
  • Effects of celecoxib on other medicinal products
  • CYP2D6 inhibition

Celecoxib is an inhibitor of CYP2D6. The plasma concentrations of medicinal products that are substrates of this enzyme may be increased when celecoxib is used concomitantly. Examples of medicinal products which are metabolised by CYP2D6 are antidepressants (tricyclics and SSRIs), neuroleptics, anti-arrhythmic medicinal products, etc.

The dose of individually dose-titrated CYP2D6 substrates may need to be reduced when treatment with celecoxib is initiated or increased if treatment with celecoxib is terminated. Concomitant administration of celecoxib 200 mg twice daily resulted in 2.6-fold and 1.5-fold increases in plasma concentrations of dextromethorphan and metoprolol (CYP2D6 substrates), respectively.

These increases are due to celecoxib inhibition of the CYP2D6 substrate metabolism. CYP2C19 inhibition In vitro studies have shown some potential for celecoxib to inhibit CYP2C19 catalysed metabolism. The clinical significance of this in vitro finding is unknown.

  • Examples of medicinal products which are metabolised by CYP2C19 are diazepam, citalopram and imipramine.
  • Methotrexate In patients with rheumatoid arthritis celecoxib had no statistically significant effect on the pharmacokinetics (plasma or renal clearance) of methotrexate (in rheumatologic doses).
  • However, adequate monitoring for methotrexate-related toxicity should be considered when combining these two medicinal products.

Lithium In healthy subjects, co-administration of celecoxib 200 mg twice daily with 450 mg twice daily of lithium resulted in a mean increase in C max of 16 % and in area under the curve (AUC) of 18 % of lithium. Therefore, patients on lithium treatment should be closely monitored when celecoxib is introduced or withdrawn.

  1. Oral contraceptives
  2. In an interaction study, celecoxib had no clinically relevant effects on the pharmacokinetics of oral contraceptives (1 mg norethisterone /35 micrograms ethinylestradiol).
  3. Glibenclamide/tolbutamide
  4. Celecoxib does not affect the pharmacokinetics of tolbutamide (CYP2C9 substrate), or glibenclamide to a clinically relevant extent.
  5. Effects of other medicinal products on celecoxib
  6. CYP2C9 poor metabolisers

In individuals who are CYP2C9 poor metabolisers and demonstrate increased systemic exposure to celecoxib, concomitant treatment with CYP2C9 inhibitors such as fluconazole could result in further increases in celecoxib exposure. Such combinations should be avoided in known CYP2C9 poor metabolisers (see sections 4.2 and 5.2).

CYP2C9 inhibitors and inducers Since celecoxib is predominantly metabolised by CYP2C9 it should be used at half the recommended dose in patients receiving fluconazole. Concomitant use of 200 mg single-dose of celecoxib and 200 mg once daily of fluconazole, a potent CYP2C9 inhibitor, resulted in a mean increase in celecoxib C max of 60% and in AUC of 130%.

Concomitant use of inducers of CYP2C9 such as rifampicin, carbamazepine and barbiturates may reduce plasma concentrations of celecoxib.

  • Ketoconazole and antacids
  • Ketoconazole or antacids have not been observed to affect the pharmacokinetics of celecoxib.
  • Paediatric population
  • Interaction studies have only been performed in adults.

Pregnancy Studies in animals (rats and rabbits) have shown reproductive toxicity, including malformations (see sections 4.3 and 5.3). Inhibition of prostaglandin synthesis might adversely affect pregnancy. Data from epidemiological studies suggest an increased risk of spontaneous abortion after use of prostaglandin synthesis inhibitors in early pregnancy. The potential for human risk in pregnancy is unknown, but cannot be excluded. Celecoxib, as with other medicinal products inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester. During the second or third trimester of pregnancy, NSAIDs including celecoxib may cause fetal renal dysfunction which may result in reduction of amniotic fluid volume or oligohydramnios in severe cases. Such effects may occur shortly after treatment initiation and are usually reversible upon discontinuation. Celecoxib is contraindicated in pregnancy and in women who can become pregnant (see sections 4.3 and 4.4). If a woman becomes pregnant during treatment, celecoxib should be discontinued. Breast-feeding Celecoxib is excreted in the milk of lactating rats at concentrations similar to those in plasma. Administration of celecoxib to a limited number of lactating women has shown a very low transfer of celecoxib into breast milk. Women who take Celebrex should not breastfeed. Fertility Based on the mechanism of action, the use of NSAIDs, including celecoxib, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Celebrex may have minor influence on the ability to drive and use machines. Patients who experience dizziness, vertigo or somnolence while taking Celebrex should refrain from driving or operating machinery. Adverse reactions are listed by system organ class and ranked by frequency in Table 1, reflecting data from the following sources: • Adverse reactions reported in osteoarthritis patients and rheumatoid arthritis patients at incidence rates greater than 0.01 % and greater than those reported for placebo during 12 placebo- and/or active-controlled clinical trials of duration up to 12 weeks at celecoxib daily doses from 100 mg up to 800 mg. In additional studies using non-selective NSAID comparators, approximately 7 400 arthritis patients have been treated with celecoxib at daily doses up to 800 mg, including approximately 2 300 patients treated for 1 year or longer. The adverse reactions observed with celecoxib in these additional studies were consistent with those for osteoarthritis and rheumatoid arthritis patients listed in Table 1, • Adverse reactions reported at incidence rates greater than placebo for subjects treated with celecoxib 400 mg daily in long-term polyp prevention trials of duration up to 3 years (the Adenoma Prevention with Celecoxib (APC) and Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP) trials; see section 5.1, Cardiovascular safety – long-term studies involving patients with sporadic adenomatous polyps). • Adverse drug reactions from post-marketing surveillance as spontaneously reported during a period in which an estimated >70 million patients were treated with celecoxib (various doses, durations, and indications). Even though these were identified as reactions from post-marketing reports, trial data was consulted to estimate frequency. Frequencies are based on a cumulative meta-analysis with pooling of trials representing exposure in 38102 patients. Table 1. Adverse drug reactions in celecoxib clinical trials and surveillance experience (MedDRA preferred terms) 1,2

Adverse Drug Reaction Frequency
System organ class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Rare (≥ 1/10,000 to < 1/1,000) Very rare (< 1/10,000) Not known (cannot be estimated from available data)
Infections and infestations Sinusitis, upper respiratory tract infection, pharyngitis,urinary tract infection
Blood and lymphatic system disorders Anaemia Leukopenia, thrombo-cytopenia Pancytopenia 4
Immune system disorders Hypersensitivity Anaphylactic shock 4, anaphylactic reaction 4
Metabolism and nutrition disorders Hyperkalaemia
Psychiatric disorders Insomnia Anxiety, depression, fatigue Confusional state, hallucinations 4
Nervous system disorders Dizziness, hypertonia, headache 4 Cerebral infarction 1, paraesthesia, somnolence Ataxia, dysgeusia Haemorrhage intracranial (including fatal intracranial haemorrhage) 4, meningitis aseptic 4, epilepsy (including aggravated epilepsy) 4, ageusia 4, anosmia 4
Eye disorders Vision blurred, conjunctivitis 4 Eye haemorrhage 4 Retinal artery occlusion 4, retinal vein occlusion 4
Ear and labyrinth disorders Tinnitus, hypoacusis 1
Cardiac disorders Myocardial infarction 1 Cardiac failure, palpitations, tachycardia Arrhythmia 4
Vascular disorders Hyper-tension 1 (including aggravated hyper-tension) Pulmonary embolism 4, flushing 4 Vasculitis 4
Respiratory, thoracic, and mediastinal disorders Rhinitis, cough, dyspnoea 1 Bronchospasm 4 Pneumonitis 4
Gastrointestinal disorders Nausea 4, abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting 1, dysphagia 1 Constipation, gastritis, stomatitis, gastrointestinal inflammation (including aggravation of gastrointestinal inflammation), eructation Gastro-intestinal haemorrhage 4, duodenal ulcer, gastric ulcer, oesophageal ulcer, intestinal ulcer, large intestinal ulcer, intestinal perforation, oesophagitis, melaena, pancreatitis, colitis 4
Hepatobiliary disorders Hepatic function abnormal, hepatic enzyme increased (including increased SGOT and SGPT) Hepatitis 4 Hepatic failure 4 (sometimes fatal or requiring liver transplant), hepatitis fulminant 4 (some with fatal outcome), hepatic necrosis 4, cholestasis 4, hepatitis cholestatic 4, jaundice 4
Skin and subcutaneous tissue disorders Rash, pruritus (includes pruritus generalised) Urticaria, ecchymosis 4 Angioedema 4, alopecia, photo-sensitivity Dermatitis exfoliative 4, erythema multiforme 4, Stevens-Johnson syndrome 4, toxic epidermal necrolysis 4, drug reaction with eosinophilia and systemic symptoms (DRESS) 4, acute generalised exanthematous pustulosis (AGEP) 4, dermatitis bullous 4
Musculoskeletal and connective tissue disorders Arthralgia 4 Muscle spasms (leg cramps) Myositis 4
Renal and urinary disorders Blood creatinine increased, blood urea increased Renal failure acute 4, hypo-natraemia 4 Tubulointerstitial nephritis 4, nephrotic syndrome 4, glomerulonephritis minimal lesion 4
Reproductive system and breast disorders Menstrual disorder 4 Infertility female (female fertility decreased) 3
General disorders and administrative site conditions Influenza-like illness, oedema peripheral/ fluid retention Face oedema, chest pain 4
Injury, poisoning and procedural complications Injury (accidental injury)
SGOT – serum glutamic oxaloacetic transaminase SGPT – serum glutamic pyruvic transaminase 1 Adverse drug reactions that occurred in polyp prevention trials, representing subjects treated with celecoxib 400 mg daily in 2 clinical trials of duration up to 3 years (the APC and PreSAP trials). The adverse drug reactions listed above for the polyp prevention trials are only those that have been previously recognised in the post-marketing surveillance experience, or have occurred more frequently than in the arthritis trials.2 Furthermore, the following previously unknown adverse reactions occurred in polyp prevention trials, representing subjects treated with celecoxib 400 mg daily in 2 clinical trials of duration up to 3 years (the APC and PreSAP trials): Common: angina pectoris, irritable bowel syndrome, nephrolithiasis, blood creatinine increased, benign prostatic hyperplasia, weight increased. Uncommon: helicobacter infection, herpes zoster, erysipelas, bronchopneumonia, labyrinthitis, gingival infection, lipoma, vitreous floaters, conjunctival haemorrhage, deep vein thrombosis, dysphonia, haemorrhoidal haemorrhage, frequent bowel movements, mouth ulceration, allergic dermatitis, ganglion, nocturia, vaginal haemorrhage, breast tenderness, lower limb fracture, blood sodium increased.3 Women intending to become pregnant are excluded from all trials, thus consultation of the trial database for the frequency of this event was not reasonable.4 Frequencies are based on cumulative meta-analysis with pooling of trials representing exposure in 38102 patients.

In final data (adjudicated) from the APC and PreSAP trials in patients treated with celecoxib 400 mg daily for up to 3 years (pooled data from both trials; see section 5.1 for results from individual trials), the excess rate over placebo for myocardial infarction was 7.6 events per 1,000 patients (uncommon) and there was no excess rate for stroke (types not differentiated) over placebo. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. There is no clinical experience of overdose. Single-doses up to 1200 mg and multiple doses up to 1200 mg twice daily have been administered to healthy subjects for nine days without clinically significant adverse effects. In the event of suspected overdose, appropriate supportive medical care should be provided e.g. by eliminating the gastric contents, clinical supervision and, if necessary, the institution of symptomatic treatment. Dialysis is unlikely to be an efficient method of medicinal product removal due to high protein binding. Pharmacotherapeutic group: Non-steroidal anti-inflammatory and antirheumatic drugs, NSAIDs, Coxibs, ATC code: M01AH01. Mechanism of action Celecoxib is an oral, selective, COX-2 inhibitor within the clinical dose range (200-400 mg daily). No statistically significant inhibition of COX-1 (assessed as ex vivo inhibition of thromboxane B 2 formation) was observed in this dose range in healthy volunteers. Pharmacodynamic effects Cyclooxygenase is responsible for generation of prostaglandins. Two isoforms, COX-1 and COX-2, have been identified. COX-2 is the isoform of the enzyme that has been shown to be induced by pro-inflammatory stimuli and has been postulated to be primarily responsible for the synthesis of prostanoid mediators of pain, inflammation, and fever. COX-2 is also involved in ovulation, implantation and closure of the ductus arteriosus, regulation of renal function, and central nervous system functions (fever induction, pain perception and cognitive function). It may also play a role in ulcer healing. COX-2 has been identified in tissue around gastric ulcers in humans but its relevance to ulcer healing has not been established. The difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and COX-2 selective inhibitors may be of clinical significance in patients at risk of thrombo-embolic reactions. COX-2 selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting platelet thromboxane. Celecoxib is a diaryl-substituted pyrazole, chemically similar to other non-arylamine sulfonamides (e.g. thiazides, furosemide) but differs from arylamine sulfonamides (e.g. sulfamethoxizole and other sulfonamide antibiotics). A dose-dependent effect on TxB 2 formation has been observed after high doses of celecoxib. However, in healthy subjects, in small multiple dose studies with 600 mg BID (three times the highest recommended dose) celecoxib had no effect on platelet aggregation and bleeding time compared to placebo. Clinical efficacy and safety Several clinical studies have been performed confirming efficacy and safety in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Celecoxib was evaluated for the treatment of the inflammation and pain of osteoarthritis of the knee and hip in approximately 4200 patients in placebo and active-controlled trials of up to 12 weeks duration. It was also evaluated for treatment of the inflammation and pain of rheumatoid arthritis in approximately 2100 patients in placebo and active-controlled trials of up to 24 weeks duration. Celecoxib at daily doses of 200 mg – 400 mg provided pain relief within 24 hours of dosing. Celecoxib was evaluated for the symptomatic treatment of ankylosing spondylitis in 896 patients in placebo and active-controlled trials of up to 12 weeks duration. Celecoxib at doses of 100 mg BID, 200 mg QD, 200 mg BID and 400 mg QD in these studies demonstrated significant improvement in pain, global disease activity and function in ankylosing spondylitis. Five randomised double-blind controlled studies have been conducted including scheduled upper gastrointestinal endoscopy in approximately 4500 patients free from initial ulceration (celecoxib doses from 50 mg – 400 mg BID). In twelve week endoscopy studies celecoxib (100 – 800 mg per day) was associated with a significantly lower risk of gastroduodenal ulcers compared with naproxen (1000 mg per day) and ibuprofen (2400 mg per day). The data were inconsistent in comparison with diclofenac (150 mg per day). In two of the 12-week studies the percentage of patients with endoscopic gastroduodenal ulceration was not significantly different between placebo and celecoxib 200 mg BID and 400 mg BID. In a prospective long-term safety outcome study (6 to 15 month duration, CLASS study), 5,800 osteoarthritis and 2,200 rheumatoid arthritis patients received celecoxib 400 mg BID (4-fold and 2-fold the recommended osteoarthritis and rheumatoid arthritis doses, respectively), ibuprofen 800 mg ter in die (TID) or diclofenac 75 mg BID (both at therapeutic doses). Twenty-two percent of enrolled patients took concomitant low-dose acetylsalicylic acid (≤325 mg/day), primarily for CV prophylaxis. For the primary endpoint complicated ulcers (defined as gastrointestinal bleeding, perforation or obstruction) celecoxib was not significantly different than either ibuprofen or diclofenac individually. Also for the combined NSAID group there was no statistically significant difference for complicated ulcers (relative risk 0.77, 95 % CI 0.41-1.46, based on entire study duration). For the combined endpoint, complicated and symptomatic ulcers, the incidence was significantly lower in the celecoxib group compared to the NSAID group, relative risk 0.66, 95 % CI 0.45-0.97 but not between celecoxib and diclofenac. Those patients on celecoxib and concomitant low-dose acetylsalicylic acid experienced 4-fold higher rates of complicated ulcers as compared to those on celecoxib alone. The incidence of clinically significant decreases in haemoglobin (>2 g/dL), confirmed by repeat testing, was significantly lower in patients on celecoxib compared to the NSAID group, relative risk 0.29, 95 % CI 0.17- 0.48. The significantly lower incidence of this event with celecoxib was maintained with or without acetylsalicylic acid use. In a prospective randomised 24 week safety study in patients who were aged ≥60 years or had a history of gastroduodenal ulcers, the percentages of patients with decreases in haemoglobin (≥2 g/dL) and/or haematocrit (≥10 %) of defined or presumed GI origin were lower in patients treated with celecoxib 200 mg twice daily (N=2238) compared to patients treated with diclofenac SR 75 mg twice daily plus omeprazole 20 mg once daily (N=2246) (0.2 % vs.1.1 % for defined GI origin, p = 0.004; 0.4 % vs.2.4 % for presumed GI origin, p = 0.0001). The rates of clinically manifest GI complications such as perforation, obstruction or haemorrhage were very low with no differences between the treatment groups (4-5 per group). Cardiovascular safety – long-term studies involving subjects with sporadic adenomatous polyps Two studies involving subjects with sporadic adenomatous polyps were conducted with celecoxib i.e., the APC trial and the PreSAP trial. In the APC trial, there was a dose-related increase in the composite endpoint of CV death, myocardial infarction, or stroke (adjudicated) with celecoxib compared to placebo over 3 years of treatment. The PreSAP trial did not demonstrate a statistically significant increased risk for the same composite endpoint. In the APC trial, the relative risks compared to placebo for a composite endpoint (adjudicated) of CV death, myocardial infarction, or stroke were 3.4 (95 % CI 1.4 – 8.5) with celecoxib 400 mg twice daily and 2.8 (95 % CI 1.1 – 7.2) with celecoxib 200 mg twice daily. Cumulative rates for this composite endpoint over 3 years were 3.0 % (20/671 subjects) and 2.5 % (17/685 subjects), respectively, compared to 0.9 % (6/679 subjects) for placebo. The increases for both celecoxib dose groups versus placebo were mainly due to an increased incidence of myocardial infarction. In the PreSAP trial, the relative risk compared to placebo for this same composite endpoint (adjudicated) was 1.2 (95 % CI 0.6 – 2.4) with celecoxib 400 mg once daily compared to placebo. Cumulative rates for this composite endpoint over 3 years were 2.3 % (21/933 subjects) and 1.9 % (12/628 subjects), respectively. The incidence of myocardial infarction (adjudicated) was with 1.0 % (9/933 subjects) with celecoxib 400 mg once daily and 0.6 % (4/628 subjects) with placebo. Data from a third long-term study, ADAPT (The Alzheimer’s Disease Anti-inflammatory Prevention Trial), did not show a significantly increased CV risk with celecoxib 200 mg BID compared to placebo. The relative risk compared to placebo for a similar composite endpoint (CV death, myocardial infarction, stroke) was 1.14 (95 % CI 0.61 – 2.15) with celecoxib 200 mg twice daily. The incidence of myocardial infarction was 1.1 % (8/717 patients) with celecoxib 200 mg twice daily and 1.2 % (13/1070 patients) with placebo. Prospective randomised evaluation of celecoxib integrated safety vs. ibuprofen or naproxen (PRECISION) The PRECISION study was a double-blind study of cardiovascular safety in Osteo arthritis (OA) or Rheumatoid arthritis (RA) patients with or at high risk for cardiovascular disease comparing Celecoxib (200-400 mg daily) with Naproxen (750-1 000 mg daily) and Ibuprofen (1 800-2 400 mg daily). The primary endpoint, Antiplatelet Trialists Collaboration (APTC), was an independently adjudicated composite of cardiovascular death (including haemorrhagic death), non-fatal myocardial infarction or non-fatal stroke. The study was planned with 80% power to evaluate non-inferiority. All patients were prescribed open-label esomeprazole (20-40 mg) for gastro protection. Patients who were taking low-dose aspirin were permitted to continue therapy, at baseline nearly half of the subjects were on aspirin. Secondary and tertiary endpoints included cardiovascular, gastrointestinal and renal outcomes. The Average Dose dispensed was 209±37 mg/day for Celecoxib, 2045±246 for Ibuprofen and 852±103 for Naproxen, Regarding the primary endpoint, Celecoxib, as compared with either naproxen or ibuprofen, met all four pre-specified non-inferiority requirements, see Table 2. Other independently adjudicated secondary and tertiary endpoints included cardiovascular, gastrointestinal and renal outcomes. Additionally, there was a 4-month substudy focusing on the effects of the three medicinal products on blood pressure as measured by ambulatory monitoring (ABPM). Table 2. Primary analysis of the adjudicated APTC composite endpoint

Intent-To-Treat Analysis (ITT, through month 30)
Celecoxib 100-200 mg bid Ibuprofen 600-800 mg tid Naproxen 375-500 mg bid
N 8,072 8,040 7,969
Subjects with Events 188 (2.3%) 218 (2.7%) 201 (2.5%)
Pairwise Comparison Celecoxib vs. Naproxen Celecoxib vs. Ibuprofen Ibuprofen vs. Naproxen
HR (95% CI) 0.93 (0.76, 1.13) 0.86 (0.70, 1.04) 1.08 (0.89, 1.31)
Modified Intent-To-Treat Analysis (mITT, on treatment through month 43)
Celecoxib 100-200 mg bid Ibuprofen 600-800 mg tid Naproxen 375-500 mg bid
N 8,030 7,990 7,933
Subjects with Events 134 (1.7%) 155 (1.9%) 144 (1.8%)
Pairwise Comparison Celecoxib vs. Naproxen Celecoxib vs. Ibuprofen Ibuprofen vs. Naproxen
HR (95% CI) 0.90 (0.72, 1.14) 0.81 (0.64, 1.02) 1.12 (0.889, 1.40)

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  • HR – hazard Ratio
  • BID – bis in die
  • TID – ter in die
  • The results were overall numerically similar in the celecoxib and comparator groups for the secondary and tertiary endpoints and there were overall no unexpected safety findings.
  • Taken together the PRECISION study indicates that celecoxib at the lowest approved dose of 100 mg twice daily is non-inferior to ibuprofen dosed in the range of 600 mg-800 mg three times daily or naproxen dosed in the range of 375 mg-500 mg twice daily with respect to cardiovascular adverse effects.

    The cardiovascular risks of the NSAID class, including coxibs, are dose-dependent, therefore, the results for celecoxib 200 mg daily on the composite cardiovascular endpoint cannot be extrapolated to dosing regimens using the higher doses of celecoxib. Absorption Celecoxib is well absorbed reaching peak plasma concentrations after approximately 2-3 hours.

    Dosing with food (high fat meal) delays absorption of celecoxib by about 1 hour resulting in a T max of about 4 hours and increases bioavailability by about 20%. In healthy adult volunteers, the overall systemic exposure (AUC) of celecoxib was equivalent when celecoxib was administered as intact capsule or capsule contents sprinkled on applesauce.

    • Distribution
    • Plasma protein binding is about 97 % at therapeutic plasma concentrations and the medicinal product is not preferentially bound to erythrocytes.
    • Biotransformation

    Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, inactive as COX-1 or COX-2 inhibitors, have been identified in human plasma i.e., a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate. Cytochrome P450 2C9 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity, such as those homozygous for the CYP2C9*3 polymorphism. In a pharmacokinetic study of celecoxib 200 mg administered once daily in healthy volunteers, genotyped as either CYP2C9*1/*1, CYP2C9*1/*3, or CYP2C9*3/*3, the median C max and AUC 0-24 of celecoxib on day 7 were approximately 4-fold and 7-fold, respectively, in subjects genotyped as CYP2C9*3/*3 compared to other genotypes. In three separate single-dose studies, involving a total of 5 subjects genotyped as CYP2C9*3/*3, single-dose AUC 0-24 increased by approximately 3-fold compared to normal metabolisers. It is estimated that the frequency of the homozygous *3/*3 genotype is 0.3-1.0 % among different ethnic groups. Patients who are known, or suspected to be CYP2C9 poor metabolisers based on previous history/experience with other CYP2C9 substrates should be administered celecoxib with caution (see section 4.2). No clinically significant differences were found in Pharmacokinetic parameters of celecoxib between elderly African-Americans and Caucasians. The plasma concentration of celecoxib is approximately 100 % increased in elderly women (>65 years). Compared to subjects with normal hepatic function, patients with mild hepatic impairment had a mean increase in C max of 53 % and in AUC of 26 % of celecoxib. The corresponding values in patients with moderate hepatic impairment were 41 % and 146 % respectively. The metabolic capacity in patients with mild to moderate impairment was best correlated to their albumin values. Treatment should be initiated at half the recommended dose in patients with moderate liver impairment (with serum albumin 25-35 g/l). Patients with severe hepatic impairment (serum albumin <25 g/l) have not been studied and celecoxib is contraindicated in this patient group. There is little experience of celecoxib in renal impairment. The pharmacokinetics of celecoxib has not been studied in patients with renal impairment but is unlikely to be markedly changed in these patients. Thus caution is advised when treating patients with renal impairment. Severe renal impairment is contraindicated. Elimination Celecoxib is mainly eliminated by metabolism. Less than 1 % of the dose is excreted unchanged in urine. The inter-subject variability in the exposure of celecoxib is about 10-fold. Celecoxib exhibits dose- and time-independent pharmacokinetics in the therapeutic dose range. Elimination half-life is 8-12 hours. Steady state plasma concentrations are reached within 5 days of treatment. Non-clinical safety data revealed no special hazard for humans based on conventional studies of repeated dose toxicity, mutagenicity or carcinogenicity beyond those addressed in section 4.4, 4.6, and 5.1 of the SmPC. Celecoxib at oral doses ≥150 mg/kg/day (approximately 2-fold human exposure at 200 mg twice daily as measured by AUC 0-24 ), caused an increased incidence of ventricular septal defects, a rare event, and fetal alterations, such as ribs fused, sternebrae fused and sternebrae misshapen when rabbits were treated throughout organogenesis. A dose-dependent increase in diaphragmatic hernias was observed when rats were given celecoxib at oral doses ≥30 mg/kg/day (approximately 6-fold human exposure based on the AUC 0-24 at 200 mg twice daily) throughout organogenesis. These effects are expected following inhibition of prostaglandin synthesis. In rats, exposure to celecoxib during early embryonic development resulted in pre-implantation and post-implantation losses, and reduced embryo/fetal survival. Celecoxib was excreted in rat milk. In a peri-post natal study in rats, pup toxicity was observed. In a 2 year toxicity study an increase in nonadrenal thrombosis was observed in male rat at high doses.

    1. Capsules content
    2. Lactose monohydrate
    3. Sodium laurilsulfate
    4. Povidone
    5. Croscarmellose sodium
    6. Magnesium stearate
    7. Capsule shells
    8. Gelatin
    9. Titanium dioxide E171
    10. Sodium laurilsulfate
    11. Sorbitan monolaurate
    12. Printing ink
    13. Iron oxide E172
    14. Shellac
    15. Propylene glycol

    Do not store above 30 °C. Clear or opaque PVC/aluminium blisters. Pack of 2, 5, 6, 10, 20, 30, 40, 50, 60, 100, 10×10, 10×30, 10×50, 1×50 unit dose, 1×100 unit dose, 5x(10×10). Not all pack sizes may be marketed. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

    • Upjohn UK Limited
    • Ramsgate Road
    • Sandwich
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    • United Kingdom

    : Celebrex 200 mg capsule

    How long does Celebrex 200 mg last?

    6. Response and effectiveness –

    Celebrex takes approximately 3 hours after oral administration to reach peak concentrations. The pain-relieving effects of Celebrex last for approximately 12 hours.

    Which is better for inflammation Celebrex or Aleve?

    Summary. Celecoxib (Celebrex) works well for treating pain and swelling with less stomach upset than similar alternatives, but might not be a good option if you have heart problems or a sulfa allergy. Naproxen (Aleve) works well for treating inflammation and a variety of mild-to-moderate pain conditions.

    Is Celebrex hard on your heart?

    Study links Celebrex, heart valve calcification after earlier research declared drug safe A well-known, four-year study found popular arthritis drug Celebrex no more dangerous for the heart than older drugs in its same classification – commonly called NSAIDs.

    Now, a big-data analysis of patient records at Vanderbilt University has found a link specifically between Celebrex and heart valve calcification., professor of biomedical engineering, and Ph.D. student Meghan Bowler started out by testing celecoxib, the active compound in Celebrex, on valve cells in an effort to see if it could double as an aortic stenosis therapy.

    It made the problem worse. To confirm their theory about a link between celecoxib and valve calcification, Merryman, who is also a professor of pharmacology, medicine and pediatrics at Vanderbilt, recruited Michael Raddatz, an M.D./Ph.D. student, to analyze more than 8,600 relevant, anonymous patient records from Vanderbilt University Medical Center.

    Raddatz checked whether there was a link between Celebrex use and aortic valve disease, and, after correcting for other risk factors, discovered that patients who had taken Celebrex had a 35 percent increased prevalence of valve disease. “If we extrapolate data from the cohort of patients we studied, in the 9 million Americans who are prescribed celecoxib every year, an additional 297,000 will develop aortic sclerosis than if they had been taking other NSAIDs,” Merryman said.

    The team’s in the Journal of the American College of Cardiology (JACC): Basic to Translational Science. Feb.22 is, The 2016 New England Journal of Medicine that found Celebrex no more damaging than naproxen and ibuprofen only looked at cardiovascular death and nonfatal heart attack or stroke, not valve disease, which affects more than a quarter of the U.S.

    1. Population older than 65.
    2. In this study, we’re adding a long-term perspective on celecoxib use,” said Bowler, who recently earned her Ph.D.
    3. In biomedical engineering.
    4. Calcification in the aortic valve can take many years.
    5. So if you’re at a higher risk for it, you might want to consider taking a different painkiller or rheumatoid arthritis treatment.” As part of the same study, Bowler and Merryman found dimethyl celecoxib – an inactive form of celecoxib – could potentially slow or stop aortic stenosis.

    Merryman said he intends to keep testing dimethyl celecoxib for its beneficial effects on heart valve health. His work was funded by the following grants: NIH R35 (HL135790), NIH R01 (HL115103), NIH T32 (GM007347), NSF CAREER Award (1055384), and NSF Graduate Research Fellowship (2013170175).

    Which is better for arthritis meloxicam or Celebrex?

    They’re similarly effective as other NSAIDs for pain relief. Meloxicam and Celebrex are both available in generic forms. Meloxicam typically costs less than generic Celebrex, making it a more affordable option. But there are still ways to save on both medications.

    Which is better for arthritis Celebrex or Tylenol?

    Compare Tylenol vs Celebrex – Iodine.com Relieves pain and fever. Tylenol Regular Strength (acetaminophen) effectively reduces fever and relieves pain, but it doesn’t lower inflammation and swelling.3.7 / 5 average rating with 1002 reviews for Tylenol Relieves pain and inflammation.

    Works well to relieve pain and fevers.Good for menstrual cramps, toothaches, body aches, and mild arthritis pain.Tylenol Regular Strength (acetaminophen) causes less upset stomach, ulcers, bruising, and bleeding than other pain medications like aspirin and Advil.Doesn’t cause kidney damage and is also safe to use if you have heart problems or if you’re pregnant.Tylenol Regular Strength (acetaminophen) has been used for a long time and is generally safe for short-term use.

    Celebrex (celecoxib) effectively relieves pain and inflammation for many types of pain conditions including osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, and menstrual cramps.Celebrex (celecoxib) causes less stomach problems compared to other NSAIDs like ibuprofen or naproxen.Celebrex (celecoxib) is available as a cheaper, generic form.Celebrex (celecoxib) has the lowest risk of heart attack compared to other NSAIDs.

    Tylenol Regular Strength (acetaminophen) doesn’t treat some kinds of pain as well as other medications like Advil.Drinking alcohol while taking Tylenol Regular Strength (acetaminophen) can damage your liver.To avoid hurting your liver, you need to keep track of the total amount of acetaminophen you are taking since it’s a very common ingredient in pain and cold combination medicines.Heavy alcohol drinkers and people with liver problems should avoid using Tylenol Regular Strength (acetaminophen) since it can cause serious liver damage.

    The longer you take Celebrex (celecoxib), the more likely you are to have stomach problems, including inflammation, ulcers, and bleeding.Celebrex (celecoxib) can affect your kidneys or cause permanent kidney damage if taken for a long time.Celebrex (celecoxib) shouldn’t be used if you have an allergy to sulfa medications.

    PillChewable tabletDissolving tabletLiquidSuppositoryInjection

    Want to save even more money? The Tylenol Regular Strength (acetaminophen) FDA package insert doesn’t have numbers about how common side effects are.

    Upper respiratory infection

    Accidental overdose and death

    Medication administering errorsInjection formulationExceeding the recommended maximum daily limits

    Drinking more than 2 alcoholic beverages a dayTaking with other Tylenol-containing medicinesHistory of liver disease

    Long-term useHistory of heart diseaseHistory of heart bypass surgery (coronary artery bypass graft/CABG)

    Age 65 or olderHistory of GI bleed or peptic ulcer diseaseLonger duration of treatmentUse of oral corticosteroids, aspirin, anticoagulants, selective serotonin reuptake inhibitors (SSRIs)SmokingAlcohol use

    History of high blood pressure

    History of kidney problemsDehydrationHeart failureLiver problemsTaking diuretic medicationsACE inhibitorsAngiotensin II receptor blockersAge 65 or older

    : Compare Tylenol vs Celebrex – Iodine.com

    Can you take an anti-inflammatory and Tylenol together?

    Studies have shown that ibuprofen (Advil, Motrin) and acetaminophen (Tylenol) together work well to relieve certain types of pain, and with few side effects. In fact, for moderate to severe dental pain, this combination often works better than many opioid pain medications.

    Is Celebrex an anti-inflammatory or a painkiller?

    Descriptions – Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) used to treat mild to moderate pain and help relieve symptoms of arthritis (eg, osteoarthritis, rheumatoid arthritis, or juvenile rheumatoid arthritis), such as inflammation, swelling, stiffness, and joint pain.

    However, this medicine does not cure arthritis and will help you only as long as you continue to take it. Celecoxib is also used to treat ankylosing spondylitis, which is a type of arthritis that affects the joints in the spine. This medicine may also be used to treat acute pain and menstrual cramps. Celecoxib is also used to treat acute migraine headaches with or without aura.

    However, this medicine is not used to prevent migraines. This medicine is available only with your doctor’s prescription. This product is available in the following dosage forms:

    • Capsule
    • Solution

    Is Celebrex hard on your heart?

    Study links Celebrex, heart valve calcification after earlier research declared drug safe A well-known, four-year study found popular arthritis drug Celebrex no more dangerous for the heart than older drugs in its same classification – commonly called NSAIDs.

    Now, a big-data analysis of patient records at Vanderbilt University has found a link specifically between Celebrex and heart valve calcification., professor of biomedical engineering, and Ph.D. student Meghan Bowler started out by testing celecoxib, the active compound in Celebrex, on valve cells in an effort to see if it could double as an aortic stenosis therapy.

    It made the problem worse. To confirm their theory about a link between celecoxib and valve calcification, Merryman, who is also a professor of pharmacology, medicine and pediatrics at Vanderbilt, recruited Michael Raddatz, an M.D./Ph.D. student, to analyze more than 8,600 relevant, anonymous patient records from Vanderbilt University Medical Center.

    Raddatz checked whether there was a link between Celebrex use and aortic valve disease, and, after correcting for other risk factors, discovered that patients who had taken Celebrex had a 35 percent increased prevalence of valve disease. “If we extrapolate data from the cohort of patients we studied, in the 9 million Americans who are prescribed celecoxib every year, an additional 297,000 will develop aortic sclerosis than if they had been taking other NSAIDs,” Merryman said.

    The team’s in the Journal of the American College of Cardiology (JACC): Basic to Translational Science. Feb.22 is, The 2016 New England Journal of Medicine that found Celebrex no more damaging than naproxen and ibuprofen only looked at cardiovascular death and nonfatal heart attack or stroke, not valve disease, which affects more than a quarter of the U.S.

    Population older than 65. “In this study, we’re adding a long-term perspective on celecoxib use,” said Bowler, who recently earned her Ph.D. in biomedical engineering. “Calcification in the aortic valve can take many years. So if you’re at a higher risk for it, you might want to consider taking a different painkiller or rheumatoid arthritis treatment.” As part of the same study, Bowler and Merryman found dimethyl celecoxib – an inactive form of celecoxib – could potentially slow or stop aortic stenosis.

    Merryman said he intends to keep testing dimethyl celecoxib for its beneficial effects on heart valve health. His work was funded by the following grants: NIH R35 (HL135790), NIH R01 (HL115103), NIH T32 (GM007347), NSF CAREER Award (1055384), and NSF Graduate Research Fellowship (2013170175).