Active ingredients: Celecoxib
Celebrex 100 mg hard capsules
Celebrex 200 mg hard capsules
Indications Why is Celebrex used? What is it for?
Celebrex is used for the symptomatic treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.
Celebrex belongs to a class of medicines called non-steroidal anti-inflammatory drugs (NSAIDs), and more specifically to a sub-group known as COX-2 inhibitors. The body produces prostaglandins, which can cause pain and inflammation. In certain conditions such as rheumatoid arthritis and osteoarthritis, the body produces more of them. Celebrex works by reducing the production of prostaglandins, thereby also reducing pain and inflammation.
Contraindications When Celebrex should not be used
Tell your doctor if any of the following apply to you, as patients with these conditions should not take Celebrex.
- if you are allergic to celecoxib or any of the other ingredients of this medicine
- if you have ever had an allergic reaction to a class of medicines called "sulfonamides" (eg some antibiotics used to treat infections)
- if you currently have a "stomach or bowel ulcer," or "stomach or bowel" bleeding
- if, due to taking acetylsalicylic acid or any other anti-inflammatory or pain relieving drug (NSAID), you have had asthma, nasal polyps, severe nasal congestion, or an allergic reaction such as itchy skin rash, swelling of the face, lips, tongue or throat, difficulty in breathing or wheezing
- if you are pregnant. If you can become pregnant during treatment, you should discuss contraception with your doctor.
- if you are breastfeeding
- if you have severe liver disease
- if you have severe kidney disease
- if you have an inflammatory bowel disease such as ulcerative colitis or Crohn's disease
- if you have "heart failure, or known ischemic heart disease, or cerebrovascular disease, for example you have been diagnosed with a heart attack, stroke or transient ischemic attack (temporary reduction in blood supply to the brain, also known as" mini stroke "), an" angina, or a blockage of blood vessels to the heart or brain
- if you have or have had circulatory problems (peripheral arterial disease) or if you have had an "operation on the arteries of the legs
Precautions for use What you need to know before taking Celebrex
Celebrex has been prescribed for you by your doctor. The following information will help you get the best results with Celebrex. If you have any further questions, ask your doctor or pharmacist.
Talk to your doctor before taking Celebrex:
- if you have previously had an "ulcer or" bleeding in the stomach or intestines (do not take Celebrex if you currently have an "ulcer or" bleeding in the stomach or intestines)
- if you take acetylsalicylic acid (even at low doses used for heart protection)
- if you use medicines to reduce blood clotting (e.g. warfarin)
- if you use Celebrex at the same time as other NSAIDs other than acetylsalicylic acid, such as ibuprofen or diclofenac. Concomitant use of these medicinal products should be avoided
- if you smoke, have diabetes, high blood pressure or high cholesterol
- if you have a heart, liver or kidney that is not working well, your doctor may have regular check-ups
- if you have fluid retention (such as swollen ankles and feet)
- if you are dehydrated, for example due to illness, diarrhea or the use of diuretics (used to treat excess fluid in the body)
- if you have had a severe allergic reaction or a severe skin reaction to any medicine
- if you feel sick from an "infection or think you have an" infection, as Celebrex can mask a fever or other signs of infection and inflammation
- if you are over 65, your doctor may check you regularly
As with other NSAIDs (e.g. ibuprofen or diclofenac), this medicine can lead to an increase in blood pressure and therefore your doctor may ask you to check your blood pressure on a regular basis.
A few cases of severe hepatic reactions, including severe liver inflammation, liver damage, liver failure (some cases had a fatal outcome or required liver transplantation) have been reported during treatment with celecoxib. Of the cases for which time to onset is known, most severe hepatic reactions occurred within one month of starting treatment.
Celebrex can make trying to get pregnant more difficult. You should tell your doctor if you are planning to become pregnant or if you have problems getting pregnant (see section on pregnancy and breast-feeding).
Interactions Which drugs or foods may change the effect of Celebrex
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines:
- Dextromethorphan (used to treat cough)
- ACE inhibitors or angiotensin II antagonists (used for high blood pressure and heart failure)
- Diuretics (used to treat excess fluid in the body)
- Fluconazole and rifampicin (used to treat fungal and bacterial infections)
- Warfarin or other oral anticoagulants (drugs that reduce blood clotting)
- Lithium (used to treat some types of depression)
- Other medicines to treat depression, sleep disturbances, high blood pressure or an irregular heartbeat
- Neuroleptics (used to treat some mental disorders)
- Methotrexate (used to treat rheumatoid arthritis, psoriasis and leukemia)
- Carbamazepine (used to treat epilepsy / seizures and some forms of pain or depression)
- Barbiturates (used to treat epilepsy / seizures and some sleep disorders)
- Ciclosporin and tracrolimus (used for suppression of the immune system, e.g. after transplants)
Celebrex can be taken with a low dose of acetylsalicic acid (75 mg per day or less). Ask your doctor for advice before taking both medicines at the same time.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Celebrex must not be used by women who are pregnant or who may become pregnant (e.g. women of childbearing potential who do not use adequate contraceptive methods) during the course of treatment. If you become pregnant while taking Celebrex you should stop treatment and contact your doctor for alternative therapy.
Fertility
NSAIDs, including Celebrex, can decrease fertility. You should tell your doctor if you are planning to become pregnant or if you have problems getting pregnant.
Driving and using machines
Before driving or operating machinery, you should be aware of how you may react to Celebrex. If you feel dizzy or drowsy after taking Celebrex, do not drive or operate machinery until these effects disappear.
Celebrex contains
Celebrex contains lactose (a type of sugar). If you have been informed that you have an "intolerance to some sugars, contact your doctor before taking this medicine.
Dose, Method and Time of Administration How to use Celebrex: Posology
Always take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist. If you believe or feel that the effect of Celebrex is too strong or too weak, talk to your doctor or pharmacist.
Your doctor will tell you what dose to take. As the risk of side effects related to heart problems may increase with increasing dose and duration of therapy, it is important that you use the lowest possible dose to control pain and should not take Celebrex for longer than necessary. to check for symptoms.
Celebrex should be swallowed whole with a drink of water. The capsules can be taken at any time of the day, with or without food. However, always try to take each dose of Celebrex at the same time every day.
Contact your doctor within two weeks of starting treatment if you feel no benefit.
For osteoarthritis the usual dose is 200 mg per day, which can be increased by your doctor to a maximum of 400 mg if needed. The usual dose is as follows:
- one 200 mg capsule once a day; or
- one 100 mg capsule twice a day.
For rheumatoid arthritis the usual dose is 200 mg per day, which can be increased by your doctor to a maximum of 400 mg if needed. The usual dose is as follows:
- one 100 mg capsule twice a day.
For ankylosing spondylitis the usual dose is 200 mg per day, which can be increased by your doctor to a maximum of 400 mg if needed.
The usual dose is as follows:
- one 200 mg capsule once a day; or
- one 100 mg capsule twice a day.
Kidney or liver problems: Make sure your doctor knows if you have liver or kidney problems, as a lower dose may be needed.
Elderly, especially those weighing less than 50 kg: if you are over 65 and especially if you weigh less than 50 kg, your doctor may check you more carefully.
You shouldn't take more than 400 mg per day.
Use in children: Celebrex is for adults only. Not to be used for children.
Overdose What to do if you have taken too much Celebrex
If you take more Celebrex than you should:
You should not take more capsules than your doctor has prescribed for you. If you take too many capsules, contact your doctor, pharmacist or hospital and take the medicine with you.
If you forget to take Celebrex:
If you forget to take a capsule, take it as soon as you remember. Do not take a double dose to make up for a forgotten dose.
If you stop taking Celebrex:
Suddenly stopping Celebrex treatment can lead to worsening of symptoms. Do not stop taking Celebrex unless your doctor has told you to. Your doctor will probably tell you to reduce the dose for a few days before giving up completely.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Celebrex
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects listed below have been seen in arthritis patients taking Celebrex. The side effects listed below marked with an asterisk (*) occurred at higher frequencies in patients taking Celebrex to prevent colon polyps. Patients in these studies took Celebrex at high doses and for a longer duration.
If any of the following occur, stop taking Celebrex and tell your doctor immediately:
If you have:
- an allergic reaction such as skin rash, swelling of the face, wheezing or difficulty breathing
- heart ailments such as chest pain
- severe stomach pain or any sign of bleeding in the stomach or intestines, such as black stools or blood in stools, or vomiting blood
- a skin reaction such as skin rash, blistering or peeling of the skin
- liver failure (symptoms of which include nausea, diarrhea, jaundice (yellowish discoloration of the skin or globe).
Very common: may affect more than 1 in 10 patients:
- High blood pressure *
Common: may affect up to 1 in 10 patients:
- Heart attack*
- Fluid retention with swollen ankles, legs and / or hands
- Urinary infections
- Shortness of breath *, sinusitis (sinus inflammation or infection, blocked or painful sinuses), runny or stuffy nose, sore throat, cough, cold, flu symptoms
- Dizziness, difficulty sleeping
- Vomiting *, stomach pain, diarrhea, indigestion, wind
- Skin rash, itching
- Muscle stiffness
- Difficulty swallowing *
- Worsening of existing allergies
Uncommon: may affect up to 1 in 100 patients:
- Stroke *
- Heart failure, palpitations, elevated heart rate
- Worsening of existing high blood pressure
- Abnormal blood tests for liver-related values
- Abnormal blood tests for kidney values
- Anemia (changes in red blood cells which can cause tiredness and shortness of breath)
- Anxiety, depression, fatigue, sleepiness, tingling sensation
- Elevated potassium levels in blood test results (may cause nausea, fatigue, muscle weakness or palpitations)
- Blurred or impaired vision, ringing in the ears, pain and sores in the mouth, difficulty hearing *
- Constipation, belching, inflammation of the stomach (indigestion, stomach pain or vomiting), worsening of inflammation of the stomach or intestines.
- Leg cramps
- Increased itchy rash (hives)
Rare: may affect up to 1 in 1,000 patients:
- Ulcers (bleeding) in the stomach, esophagus or intestines; or herniated intestine (can cause stomach pain, fever, nausea, vomiting, intestinal blockage), dark or black stools, inflammation of the esophagus (can cause difficulty in swallowing), inflammation of the pancreas (can cause stomach pain)
- Reduction in white blood cells (which help protect the body from infection) and platelets (greater chance of bleeding or bruising)
- Difficulty coordinating muscle movements
- Feeling confused, changes in taste
- Increased sensitivity to light
- Hair loss
Very rare: may affect up to 1 in 10,000 patients:
- Serious skin conditions such as acute generalized and exanthematous pustulosis (symptoms include red, swollen skin covered with numerous small pustules)
- Liver disorders (such as cholestasis and cholestatic hepatitis, which may be accompanied by symptoms such as discolored stools, nausea and yellowing of the skin or eyes)
- Kidney disorders (such as nephrotic syndrome and minimal change disease, which may be accompanied by symptoms such as water retention (edema), foamy urine, fatigue and loss of appetite)
Not known: frequency cannot be estimated from the available data:
- Fatal cerebral hemorrhage
- Serious allergic reactions (including life-threatening anaphylactic shock) which can cause skin rash, swelling of the face, lips, mouth, tongue or throat, wheezing or difficulty breathing; difficulty swallowing)
- Bleeding in the stomach or intestines (can cause blood in the stool or vomiting), inflammation of the intestines or colon, nausea
- Serious skin conditions such as Stevens-Johnson syndrome, exfoliative dermatitis and toxic epidermal necrolysis (can cause rash, blistering or peeling of the skin)
- Delayed allergic reaction with possible symptoms such as rash, swelling of the face, fever, swollen lymph glands, abnormal blood test values (e.g. liver function, complete blood count (eosinophilia, a specific elevation of white blood cells).
- Hepatic failure, liver damage and severe liver inflammation (sometimes fatal cases or cases requiring liver transplantation). Symptoms include nausea, diarrhea, jaundice (yellowish skin or eyes), dark urine, pale stools, bleeding easily, itching or chills.
- Kidney problems (possible kidney failure, inflammation of the kidneys)
- Blood clots in the blood vessels of the lungs. Symptoms can include sudden shortness of breath, sharp pains when breathing, or fainting.
- Irregular heartbeat
- Meningitis (inflammation of the membrane covering the brain and spinal cord)
- Hallucinations
- Worsening of epilepsy (possibility of more frequent and / or more severe seizures)
- Inflamed blood vessels (can cause fever, pain, reddish patches on the skin)
- Obstruction of an "artery or vein of the eye, causing partial or total loss of vision, inflammation of the conjunctiva, bleeding of the eye"
- Reduction in red blood cells, white blood cells and platelets (can cause tiredness, bruising easily, frequent nosebleeds and increased risk of infections)
- Chest pain
- Impairment of the sense of smell
- Skin discoloration (bruising), muscle pain and weakness, joint pain
- Menstrual disturbances
- Reduced fertility in women, usually reversible
- Headache, hot flashes
- Low sodium levels in blood test results (can cause loss of appetite, headache, nausea, cramps and muscle weakness)
In clinical trials unrelated to arthritis or other arthritis-related conditions, where Celebrex was taken at doses of 400 mg per day for up to 3 years, the following side effects were observed:
Common: may affect up to 1 in 10 patients:
- Heart disorders: angina (chest pain)
- Upset stomach: irritable bowel syndrome (can include stomach pain, diarrhea, indigestion, wind)
- Kidney stones (which can cause back pain or stomach pain, blood in the urine), difficulty passing urine
- Weight gain
Uncommon: may affect up to 1 in 100 patients:
- Deep vein thrombosis (blood clotting usually in the leg, which can cause pain, swelling or redness in the calf or breathing problems)
- Stomach upset: stomach infection (which can cause stomach and intestinal irritation and ulcers)
- Fracture of the lower limbs
- Herpes zoster (St. Anthony's fire), skin infection, eczema (dry itchy rash), pneumonia (chest infection (possible cough, fever, difficulty breathing)
- Flying flies in the eye causing impaired or blurred vision, dizziness due to inner ear disorders, sore, inflamed or bleeding gums, mouth sores
- Excessive urination at night, bleeding hemorrhoids, frequent bowel movements
- Accumulations of fat on the skin or elsewhere, ganglion cyst (harmless swelling in the joints and around the tendons of the hands or feet), difficulty speaking, abnormal or very intense bleeding from the vagina, breast pain
- Elevated sodium levels in blood test results
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili.By reporting side effects you can help provide more information on the safety of this medicine
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister and carton. The expiry date refers to the last day of the month indicated.
Do not store Celebrex above 30 ° C.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Contents of the pack and other information
What Celebrex contains
The active ingredient is celecoxib.
1 capsule contains celecoxib 100 mg or 200 mg.
The excipients are:
Lactose monohydrate, sodium lauryl sulfate, povidone, croscarmellose sodium and magnesium stearate. Capsule shells contain: gelatin, titanium dioxide E171, sodium lauryl sulfate and sorbitan monolaurate. The ink contains shellac, propylene glycol, indigo carmine E132 (100 mg capsules), yellow iron oxide E172 (200 mg capsules).
What Celebrex looks like and contents of the pack
Celebrex is available in the form of hard capsules. White opaque capsules with blue bands marked 7767 and 100 (Celebrex 100 mg).
White opaque capsules with gold bands marked 7767 and 200 (Celebrex 200 mg).
The capsules are packed in clear or opaque PVC blisters or aluminum blisters.
Celebrex is contained in packs of 2 cps, 5 cps, 6 cps, 10 cps, 20 cps, 30 cps, 40 cps, 50 cps, 60 cps, 100 cps, 10 x 10 cps, 10 x 30 cps, 10 x 50 cps , 1 x 50 cps in separable units, 1 x 100 cps in separable units, 5 x (10 x 10) cps.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
CELEBREX
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 100 mg or 200 mg of celecoxib.
Celebrex capsules contain lactose (each capsule contains 149.7 mg or 49.8 mg of lactose monohydrate, respectively; see section 4.4).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Hard capsules.
White opaque capsules with blue bands marked 7767 and 100.
White opaque capsules with gold bands marked 7767 and 200.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.
The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient's overall risks (see sections 4.3 and 4.4).
04.2 Posology and method of administration
Since the cardiovascular risks of celecoxib may increase with dose and duration of exposure, the duration of treatment should be as short as possible and the lowest effective daily dose should be used. The need for treatment and response to therapy should be reassessed periodically, especially in patients with osteoarthritis (see sections 4.3, 4.4, 4.8 and 5.1).
Osteoarthritis
The recommended daily dose is 200 mg once daily or in two divided doses. In patients whose symptom relief has not been shown to be sufficient, a dose of 200 mg twice daily may increase efficacy. After two weeks of treatment, in the absence of greater therapeutic benefit, other therapeutic alternatives should be considered.
Rheumatoid arthritis
The recommended starting daily dose is 200 mg in two divided doses. If necessary, the dose can subsequently be increased up to 200 mg twice a day. After two weeks of treatment, in the absence of greater therapeutic benefit, other therapeutic alternatives should be considered.
Ankylosing spondylitis
The recommended daily dose is 200 mg once daily or in two divided doses. In patients whose symptom relief has not been shown to be sufficient, a dose of 400 mg once daily or in two divided doses may increase efficacy. After two weeks of treatment, in the absence of greater therapeutic benefit, should be evaluate other therapeutic alternatives.
The maximum recommended daily dose is 400 mg for all indications.
Celebrex can be taken with or without food.
Senior citizens
Age over 65: As in younger adults, 200 mg per day should be used initially. If necessary, the dose can subsequently be increased up to 200 mg twice a day. Special attention is required in elderly patients with body weight less than 50 kg (see sections 4.4 and 5.2).
Altered liver function
In patients with known moderate hepatic impairment (serum albumin between 25-35 g / l), treatment should be started at half the recommended dosage. Clinical experience in this group is limited to patients with liver cirrhosis (see sections 4.3, 4.4 and 5.2).
Altered kidney function
Clinical experience in patients with mild or moderate renal impairment treated with celecoxib is limited; therefore it is advised to treat this patient group with caution (see sections 4.3, 4.4 and 5.2).
Children
The use of celecoxib is not indicated in children.
Reduction of the metabolic activity of CYP2C9
Patients with known or suspected reduction in metabolic activity for CYP2C9 based on genotype or previous history / experience with other CYP2C9 substrates should be given celecoxib with caution, as the risk of dose-dependent side effects increases in In these cases, consideration should be given to halving the minimum recommended dose (see section 5.2).
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients (see section 6.1).
Known hypersensitivity to sulfonamides.
Active peptic ulcer or gastrointestinal bleeding.
Subjects in whom asthma attacks, acute rhinitis, nasal polyps, angioneurotic edema have occurred,
hives or allergic-type reactions after taking acetylsalicylic acid or non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 (cyclo-oxygenase-2) inhibitors.
Pregnancy and women of childbearing potential who do not use adequate contraceptive measures (see section 4.5). Malformations were observed in the two animal species studied with celecoxib (see sections 4.6 and 5.3). The potential risk from administration during pregnancy is unknown but cannot be excluded.
Lactation (see sections 4.6 and 5.3).
Severe hepatic insufficiency (serum albumin
Estimated renal creatinine clearance
Chronic inflammation of the intestine.
Congestive heart failure (NYHA II-IV).
Established ischemic heart disease, peripheral arterial disease and / or cerebral vascular disease.
04.4 Special warnings and appropriate precautions for use
Upper gastrointestinal complications (perforations, ulcers or bleeding), some of them fatal, have been reported in patients treated with celecoxib. Caution is advised in the treatment of patients who have an increased risk of gastrointestinal complications associated with the use of NSAIDs: the elderly, patients who are taking any other NSAIDs or acetylsalicylic acid at the same time or patients with a history of gastrointestinal diseases, such as ulcers and gastrointestinal bleeding. .
When celecoxib is taken together with acetylsalicylic acid (even in low doses) there is a further increased risk of gastrointestinal adverse events (gastrointestinal ulceration or other gastrointestinal complications).
In long-term clinical studies, no significant difference in gastrointestinal safety has been demonstrated between selective COX-2 inhibitors + acetylsalicylic acid and NSAIDs + acetylsalicylic acid (see section 5.1).
The concomitant use of celecoxib and NSAIDs other than aspirin should be avoided.
In a long-term placebo-controlled clinical study in patients with sporadic adenomatous polyposis treated with celecoxib at doses of 200 mg BID and 400 mg BID compared to placebo, an increase in the number of serious cardiovascular events, mainly myocardial infarction, was observed (see paragraph 5.1).
Since the cardiovascular risks of celecoxib may increase with dose and duration of exposure, the duration of treatment should be as short as possible and the lowest effective daily dose should be used. The need for treatment and response to therapy should be reassessed 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 (eg hypertension, hyperlipidaemia, diabetes mellitus, cigarette smoking) should only be treated with celecoxib after careful consideration (see section 5.1).
Selective COX-2 inhibitors are not a substitute for acetylsalicylic acid for the prophylaxis of thromboembolic diseases of cardiovascular origin because they do not have antiplatelet effects. Therefore, antiplatelet therapy should not be discontinued (see section 5.1).
As with other drugs that inhibit prostaglandin synthesis, fluid retention and edema have been reported in patients treated with celecoxib. Therefore, celecoxib should be used with caution in patients with a history of heart failure, left ventricular dysfunction or hypertension and in patients with other pre-existing edema, as prostaglandin inhibition may cause worsening of renal function and fluid retention. Caution is also required in patients taking diuretics or who are at risk of hypovolaemia.
Like other NSAIDs, celecoxib can lead to the onset of hypertension or worsening of pre-existing hypertension, both of which may contribute to the "increased incidence of cardiovascular events. Blood pressure should therefore be monitored closely at the initiation of therapy with celecoxib and throughout the course of treatment.
Impaired renal or hepatic function and especially impaired cardiac function are more readily found in elderly patients and therefore these patients should be kept under appropriate medical supervision.
NSAIDs, including celecoxib, can cause renal toxicity. Clinical studies conducted with celecoxib have shown effects on renal function similar to those seen with comparator NSAIDs. Patients with the highest risk of renal toxicity are those with impaired renal function, heart failure, impaired hepatic function, patients receiving diuretics, ACE inhibitors, angiotensin II receptor antagonists, and the elderly (see section 4.5). Such patients should be closely monitored during celecoxib treatment.
A few cases of severe hepatic reactions, including fulminant hepatitis (some cases with fatal outcome), hepatic necrosis and hepatic failure (some cases with fatal outcome or requiring liver transplant) have been reported during treatment with celecoxib. Of the cases for which time to onset is known, most serious hepatic adverse events developed within one month of initiation of celecoxib therapy (see section 4.8).
If deterioration of the patient's clinical condition of any of the organ systems described above occurs during the course of treatment, appropriate measures should be taken and discontinuation of celecoxib therapy should be considered.
Celecoxib inhibits cytochrome CYP2D6. Although not a strong inhibitor of this enzyme, dose reduction, on an individual basis, may be required for drugs metabolised by cytochrome CYP2D6 (see 4.5). Patients who have "reduced metabolic activity for CYP2C9 should be treated with caution (see section 5.2)."
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 increased risk for these. Adverse reactions in the initial stages of treatment: in most cases the onset of symptoms occurs within the first month of treatment. Serious hypersensitivity reactions (including anaphylaxis, angioedema, drug rash with eosinophilia and systemic symptoms (DRESS, hypersensitivity syndrome)) have been reported in patients receiving celecoxib (see section 4.8).
Patients with a history of sulphonamide allergy or other drug allergies may be at increased risk of severe skin reactions or hypersensitivity reactions (see section 4.3). Celecoxib treatment should be discontinued at the appearance of the first signs of rash, mucosal lesions or any other signs of hypersensitivity.
Celecoxib can mask febrile states and other signs of inflammation.
Severe bleeding episodes have occurred in patients taking concomitant warfarin treatment. Caution is recommended when co-administering celecoxib and warfarin and other oral anticoagulants (see section 4.5).
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, a Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Pharmacodynamic interactions
Anticoagulant activity should be monitored particularly in the first few days following initiation of treatment or dose modification of celecoxib in patients taking warfarin or other anticoagulants because these patients have an increased risk of bleeding complications. Therefore, patients on oral anticoagulants should be closely monitored for prothrombin time (INR), particularly in the first days of therapy when celecoxib treatment is initiated or when celecoxib dosage is changed (see 4.4). Bleeding episodes, some fatal, associated with increases in prothrombin time have been reported, especially in elderly patients treated with celecoxib and warfarin.
NSAIDs may reduce the effect of diuretics and antihypertensives. As with NSAIDs, the risk of acute renal failure, which is generally reversible, may increase in some patients with impaired renal function (eg dehydrated patients, patients undergoing treatment). with diuretics or the elderly) when ACE inhibitors or angiotensin II receptor antagonists are combined with NSAIDs, including celecoxib (see section 4.4). Therefore, the administration of these drugs in combination should be done with caution, especially in elderly patients. Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of treatment and on a periodic basis thereafter.
In a 28-day clinical study in patients with stage I and II hypertension controlled with lisinopril, administration of celecoxib 200 mg twice a day did not result in clinically significant increases in mean daily systolic blood pressure or diastolic, as shown by the 24-hour outpatient blood pressure check.Among patients treated with celecoxib 200 mg BID, 48% were considered unresponsive to lisinopril at the final clinical visit (patients who had either a diastolic blood pressure> 90 mmHg or an increase in diastolic blood pressure> 10% from baseline), compared to 27% of patients treated with placebo; this difference was statistically significant.
It is conceivable that co-administration of NSAIDs and cyclosporine or tacrolimus may enhance the nephrotoxic effect of cyclosporine and tacrolimus. Renal function should be monitored when celecoxib is co-administered with either of these drugs.
Celecoxib can be used in combination with low-dose acetylsalicylic acid but is not a substitute for acetylsalicylic acid for cardiovascular prophylaxis. In pivotal studies, as well as with other NSAIDs, concomitant administration of low-dose acetylsalicylic acid has shown an increase in risk of gastrointestinal ulcers or other gastrointestinal complications when compared to the use of celecoxib alone (see section 5.1).
Pharmacokinetic interactions
Effects of celecoxib on other drugs
Celecoxib is a CYP2D6 inhibitor. During treatment with celecoxib, plasma concentrations of the cytochrome CYP2D6 substrate dextromethorphan increased by 136%. Plasma concentrations of drugs interacting with this enzyme may increase when co-administered with celecoxib. Antidepressants (tricyclics and selective inhibitors of reuptake serotonin), neuroleptics, antiarrhythmics, etc. constitute an example of this category of drugs. The individually determined dose of these drugs, substrates of cytochrome CYP2D6, may require a reduction when treatment with celecoxib is started, or an increase when it is stopped.
Education in vitro demonstrated that celecoxib has some potential for inhibition of cytochrome CYP2C19 catalyzed metabolism. The clinical relevance of this phenomenon, noted in vitro, is not known. Diazepam, citalopram and imipramine are examples of drugs metabolized by cytochrome CYP2C19.
In an interaction study, celecoxib showed no clinically significant effect on the pharmacokinetics of oral contraceptives (1 mg norethisterone / 35 mg ethinyl estradiol).
Celecoxib does not alter the pharmacokinetics of tolbutamide (CYP2C9 substrate) or glibenclamide to a clinically relevant extent.
In patients with rheumatoid arthritis celecoxib did not statistically significantly alter the pharmacokinetics (plasma or renal clearance) of methotrexate (at the doses used in this disease). However, adequate monitoring of methotrexate toxicity should be considered in case of combination with celecoxib.
In healthy volunteers, co-administration of celecoxib 200 mg twice daily and 450 mg lithium twice daily resulted in a mean increase in lithium Cmax and AUC values of 16% and 18%, respectively. Therefore, patients on lithium therapy should be closely monitored when celecoxib treatment is initiated or discontinued.
Effects of other drugs on celecoxib
In patients with decreased CYP2C9 metabolic activity and increased systemic exposure to celecoxib, concomitant treatment with CYP2C9 inhibitors may further increase celecoxib exposure. In patients with known decreased metabolic activity. for CYP2C9 these combinations should be avoided (see sections 4.2 and 5.2).
Since celecoxib is primarily metabolised by cytochrome CYP2C9, patients receiving fluconazole should be treated at half the recommended dose. "Concomitant use of a single dose of celecoxib 200 mg and fluconazole 200 mg / day, a potent inhibitor of CYP2C9, caused a mean increase in celecoxib Cmax and AUC of 60% and 130%, respectively. L" Concomitant use of CYP2C9 inducers such as rifampicin, carbamazepine and barbiturates may decrease celecoxib plasma concentrations.
Ketoconazole or antacids did not alter the pharmacokinetics of celecoxib.
04.6 Pregnancy and lactation
No clinical data are available on the use of celecoxib in pregnancy. Studies in animals (rats and rabbits) have shown reproductive toxicity, including malformations (see sections 4.3 and 5.3). The potential risk from administration during pregnancy is unknown, but cannot be excluded. As with other prostaglandin synthesis inhibitor drugs, celecoxib can cause uterine inertia and premature closure of the arterial duct during the third trimester of pregnancy. Celecoxib is contraindicated in confirmed or possible pregnancy (see sections 4.3 and 4.4) If pregnancy occurs during treatment, celecoxib should be discontinued.
Celecoxib is excreted in the milk of lactating rats in concentrations similar to those found in plasma. Administration of celecoxib to a small number of lactating women has demonstrated "very low excretion of celecoxib in breast milk. Women being treated with celecoxib should not breastfeed."
04.7 Effects on ability to drive and use machines
Patients who experience dizziness, vertigo or somnolence while taking celecoxib should avoid driving or operating machinery.
04.8 Undesirable effects
Adverse reactions are listed by system organ class, and broken down by frequency in Table 1, based on data from the following sources:
• Adverse reactions reported in patients with osteoarthritis and rheumatoid arthritis, with incidences greater than 0.01% and greater than those reported for placebo, in 12 clinical trials vs placebo and / or other active control of up to 12 weeks duration , with daily dosages of celecoxib ranging from 100 mg to 800 mg. In other studies conducted with non-selective NSAIDs as comparators, approximately 7,400 patients with osteoarthritis and rheumatoid arthritis were treated with daily doses of celecoxib up to a maximum of 800 mg, including approximately 2,300 patients on treatment for one year or more. . Adverse reactions reported with celecoxib in these additional studies were consistent with those reported in patients with osteoarthritis or rheumatoid arthritis listed in Table 1.
• Adverse reactions reported at higher incidences than placebo for subjects treated with 400 mg celecoxib daily in the 3-year long-term polyposis prevention studies (APC and PreSAP studies; see section 5.1, Pharmacodynamic properties:Cardiovascular safety - Long-term studies in patients with sporadic adenomatous polyps).
• Adverse reactions resulting from post-marketing pharmacovigilance reported spontaneously over a period of time in which it is estimated that over 70 million patients have been treated with celecoxib (with different doses, durations and indications). As not all adverse drug reactions are reported to the Marketing Authorization Holder and included in the pharmacovigilance database, it is not possible to reliably determine the frequencies of these reactions.
Table 1. Adverse Reactions in Clinical Studies with Celecoxib and Post-Marketing Pharmacovigilance (MedDRA Terminology) 1,2
In the final (adjudicated) data from the APC and PreSAP studies in patients treated with celecoxib 400 mg daily for up to 3 years (combined data from both studies - see section 5.1 for individual study results), l "higher incidence of myocardial infarction compared to placebo was 7.6 events per 1,000 patients (uncommon), and there was no" higher incidence than placebo for stroke (non-differentiated types).
04.9 Overdose
No cases of overdose have been reported. Single doses up to 1200 mg and multiple doses up to 1200 mg twice daily have been administered to healthy volunteers for 9 days without clinically significant adverse events occurring. Appropriate medical care should be provided in the event of suspected overdose, such as gastric lavage, medical supervision and, if necessary, the institution of symptomatic treatment. Dialysis is not believed to be an effective method of elimination of the drug given the its high binding to plasma proteins.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Non-steroidal anti-inflammatory and antirheumatic drugs, NSAIDs, Coxibs
ATC code M01AH01
Celecoxib is a selective inhibitor of cyclo-oxygenase-2 (COX-2), effective orally, when administered at a dose of 200-400 mg / day (clinical efficacy range). At these doses, no statistically significant inhibitory effect on COX-1 (measured as inhibition) was observed in healthy volunteers. ex vivo of thromboxane B2 [TxB2]).
Cyclo-oxygenase is responsible for the formation of prostaglandins. Two isoforms of cyclo-oxygenase have been identified, COX-1 and COX-2. COX-2 has been shown to be the isoform of the enzyme induced in response to pro-inflammatory stimuli and is believed to be primarily responsible for the synthesis of prostanoids that cause pain, inflammation and fever. COX-2 is also involved in the processes of ovulation, ovum implantation and closure of the arterial duct, in the regulation of renal function and in the activity of the central nervous system (induction of fever, pain perception and cognitive function). It may also play a role in the healing of ulcers: it has in fact been isolated in the tissues surrounding gastric ulcers in humans, but its importance in the ulcer healing process has not been established.
The difference in antiplatelet activity between some COX-1 inhibitory NSAIDs and selective COX-2 inhibitors may be clinically significant in patients at risk for thromboembolic reactions. COX-2 inhibitors reduce the formation of systemic prostacyclin (and thus possibly also of the endothelial one) without acting on platelet thromboxane.
Celecoxib is a diaryl-substituted pyrazole, chemically similar to other non-arylamine sulfonamides (e.g. thiazides, furosemide) but which differs from arylamine sulfonamides (e.g. sulfamethoxazole and other sulfonamide antibiotics).
A dose-dependent effect on TxB2 was observed following the administration of high doses of celecoxib. However, in small studies conducted in healthy volunteers with multiple doses of 600 mg BID (3 times the maximum recommended dose), celecoxib showed no effect on platelet aggregation and bleeding time compared to placebo.
Numerous clinical studies have been performed which confirmed the efficacy and safety of celecoxib in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Celecoxib has been evaluated in the treatment of inflammatory and painful states in osteoarthritis of the knee and hip. in approximately 4,200 patients enrolled in clinical trials up to 12 weeks, controlled against placebo and active drugs. Celecoxib has also been evaluated for the treatment of inflammatory and painful states in rheumatoid arthritis in approximately 2,100 patients enrolled in clinical trials up to 24 weeks controlled versus placebo and active drugs. With the use of celecoxib in daily doses of 200-400 mg, a reduction in pain was achieved in less than 24 hours after administration. Celecoxib was also evaluated for the symptomatic treatment of ankylosing spondylitis in 896 patients enrolled in clinical studies up to 12 weeks controlled against placebo and active drugs. In these studies, given in doses of 100 mg BID, 200 mg QD, 200 mg BID and 400 mg QD, Celecoxib demonstrated significant improvement in pain, overall disease activity and functionality in ankylosing spondylitis.
Five double-blind, randomized, controlled studies involved endoscopic control of the upper gastrointestinal tract on approximately 4,500 patients, treated at doses of 50 - 400 mg BID of celecoxib and who had no ulceration at the start of the study. In the 12 endoscopic studies. weeks celecoxib (100-800 mg / day) was associated with a significantly lower risk of gastroduodenal ulcers than naproxen (1000 mg / day) and ibuprofen (2400 mg / day). Data were not significant compared to diclofenac (150 In two of the 12-week studies, the percentage of patients with endoscopically detected gastroduodenal ulceration was not significantly different from placebo and celecoxib 200 mg BID and 400 mg BID.
In a long-term prospective study conducted to evaluate the safety of treatment (CLASS study, duration 6-15 months), 5,800 patients with osteoarthritis and 2,200 patients with rheumatoid arthritis were treated with celecoxib 400 mg BID (4 times and 2 times, respectively) dosages recommended for osteoarthritis and rheumatoid arthritis), ibuprofen 800 mg TID or diclofenac 75 mg BID (both at therapeutic dosages). Twenty-two percent of enrolled patients were concurrently taking low-dose acetylsalicylic acid (≤ 325 mg / day), primarily for cardiovascular prophylaxis. Regarding the primary endpoint, ie the number of complicated ulcers (defined as gastrointestinal bleeding, perforation or obstruction), celecoxib was not significantly different from ibuprofen or diclofenac individually assessed. Even when the comparison was made with NSAIDs as a whole, no statistically significant difference was observed for complicated ulcers (relative risk 0.77, 95% CI 0.41-1.46, based on the entire duration of treatment). "Combined endpoint, namely complicated and symptomatic ulcers," the incidence was significantly lower in the celecoxib group than in the NSAID group (relative risk 0.66, 95% CI 0.45-0.97), although this difference was not found between celecoxib and diclofenac. A 4-fold higher frequency of complicated ulcers has been reported in patients receiving celecoxib and low-dose acetylsalicylic acid than in patients taking celecoxib alone. The incidence of clinically significant reductions in hemoglobin levels (> 2 g / dl), confirmed by repeat testing, was significantly lower in patients receiving celecoxib compared to to the group of patients treated with NSAIDs (relative risk 0.29, 95% CI 0.17-0.48). The significantly lower incidence of this event remained unaffected with or without the use of acetylsalicylic acid.
In a 24-week randomized prospective safety study in patients ≥60 years of age or who had a history of gastroduodenal ulcers (excluding those using acetylsalicylic acid), the percentages of patients with decreased hemoglobin (≥2 g / dl) and / or hematocrit (≥10%) of known or suspected gastrointestinal origin were lower in patients treated with celecoxib 200 mg BID (N = 2238) than in patients treated with prolonged-release diclofenac 75 mg BID plus omeprazole 20 mg once daily (N = 2246) (0.2% vs. 1.1% in case of established gastrointestinal origin, p = 0.004; 0.4% vs. 2.4% in case of presumed gastrointestinal origin, p = 0.0001). Clinically manifest gastrointestinal complications such as perforation, obstruction or haemorrhage were very low, with no differences between treatment groups (4-5 per group).
Cardiovascular safety - Long-term studies in patients with sporadic adenomatous polyps
Two studies were conducted with Celecoxib in patients with sporadic adenomatous polyps: the APC study (Adenoma Prevention with Celecoxib) and the PreSAP study (Prevention of Spontaneous Adenomatous Polyps). In the APC study, a dose-related increase in the combined (adjudicated) endpoint of cardiovascular death, myocardial infarction or stroke was reported with Celecoxib compared to placebo over 3 years of treatment. For the same combined endpoint, the PreSAP study did not show a statistically significant increase in risk.
In the APC study, the relative risks versus placebo for the combined (adjudicated) endpoint of cardiovascular death, myocardial infarction or stroke were 3.4 (95% CI 1.4-8.5) with 400 mg BID of celecoxib and 2.8 (95% CI 1.1-7.2) with a dose of 200 mg twice daily celecoxib. The cumulative rates over 3 years for this combined endpoint were 3.0% (20 / 671 patients) and 2.5% (17/685 patients) respectively, compared with 0.9% (6/679 patients) for placebo. The increases for both celecoxib treatment groups versus placebo were mainly due to a higher incidence of myocardial infarction.
In the PreSAP study, the relative risk versus placebo for this same combined (adjudicated) endpoint was 1.2% (95% CI 0.6 - 2.4) with single daily dose of 400 mg celecoxib, compared to placebo. . The cumulative 3-year rates for this combined endpoint were 2.3% (21/933 patients) and 1.9% (12/628 patients), respectively. The incidence of myocardial infarction (adjudicated) was 1.0% (9/933 patients) with a single daily dose of 400 mg of celecoxib and 0.6% (4/628 patients) with placebo.
Data from a third long-term study, ADAPT (The Alzheimer's Disease Anti-inflammatory Prevention Trial), did not show a significant increase in cardiovascular risk with celecoxib 200 mg BID compared to placebo. The relative risk compared to placebo for a similar combined endpoint (cardiovascular death, myocardial infarction, stroke) was 1.14 (95% CI 0.61 - 2.12) with celecoxib 200 mg twice daily. The incidence of myocardial infarction was 1 , 1% (8/717 patients) with celecoxib 200 mg BID and 1.2% (13/1070) with placebo.
05.2 Pharmacokinetic properties
Celecoxib is well absorbed and reaches peak plasma after approximately 2-3 hours. Taking it on a full stomach (high-fat meal) delays absorption by about 1 hour.
Celecoxib is mainly eliminated after metabolism; less than 1% of the dose is excreted unchanged in the urine. Subjective variability in celecoxib exposure is approximately 10-fold. Celecoxib exhibits a dose- and time-independent pharmacokinetic profile over the therapeutic dose range. At plasma concentrations corresponding to therapeutic doses, plasma protein binding is approximately 97%. Celecoxib does not preferentially bind to erythrocytes. The elimination half-life is 8-12 hours steady state they are reached within 5 days from the beginning of the treatment. The pharmacological activity is exerted by the unchanged active principle. The major metabolites found in the circulation have no detectable COX-1 or COX-2 activity.
Celecoxib metabolism is primarily mediated by cytochrome P450 2C9. Three metabolites have been identified in human plasma, inactive as inhibitors of COX-1 or COX-2, namely a primary alcohol, the corresponding carboxylic acid and its glucuroconjugate.
The activity of cytochrome P450 2C9 is reduced in subjects with genetic polymorphisms that lead to a reduction in enzyme activity, such as those homozygous for the CYP2C9 * 3 polymorphism.
In a once daily pharmacokinetic study of 200 mg celecoxib to healthy volunteers, with different genotypes such as CYP2C9 * 1 / * 1, CYP2C9 * 1 / * 3 or CYP2C9 * 3 / * 3, the median Cmax and AUC 0-24 celecoxib on day 7 were approximately 4- and 7-fold higher in subjects with the CYP2C9 * 3 / * 3 genotype, respectively, compared to the other genotypes. In three separate single dose studies, involving a total of 5 subjects with CYP2C9 * 3 genotype / * 3, AUC 0-24 per single dose nearly tripled compared to normal metabolisers. The frequency of the homozygous * 3 / * 3 genotype is estimated to be 0.3-1.0% across ethnic groups.
Patients with known or suspected decreased metabolic activity for CYP2C9 based on history / previous experience with other CYP2C9 substrates should be administered with caution (see section 4.2).
There were no clinically significant differences in celecoxib pharmacokinetic parameters between elderly African American and Caucasian patients.
The plasma concentration of celecoxib is nearly doubled in elderly women (age> 65 years).
Compared to subjects with normal hepatic function, patients with mild hepatic impairment had a mean increase in celecoxib Cmax and AUC of 53% and 26%, respectively. Corresponding values in patients with moderate hepatic impairment were 41% and 146%, respectively. The metabolic capacity in patients with mild to moderate impairment was directly related to albumin values. In patients with moderate hepatic impairment (serum albumin between 25-35 g / l), treatment should be initiated at a dose equal to half of that recommended Patients with severe hepatic impairment (serum albumin
Experience with the use of celecoxib in patients with impaired renal function is limited. The pharmacokinetics of the drug have not been studied in patients with renal impairment but it is unlikely that this will change significantly in this population. Therefore, caution is recommended when treating patients with renal impairment. The use of celecoxib in case of severe renal impairment is contraindicated.
05.3 Preclinical safety data
In conventional embryo-fetal toxicity studies, the occurrence of diaphragmatic hernia in rat fetuses and cardiovascular malformations in rabbit fetuses following systemic exposure to the free form drug was approximately 5-fold (rat) and 3-fold (rabbit). higher than the levels achieved at the maximum recommended daily dose in humans (400 mg). Diaphragmatic hernia was also observed in rats in a peri-post natal toxicity study, which included exposure during the period of Organogenesis In this study, the lowest systemic exposure at which this abnormality occurred in a single animal was estimated to be 3 times the recommended human dose.
In the animal, exposure to celecoxib during the early stages of embryonic development resulted in pre- and post-implantation losses. These effects are expected as resulting from the inhibition of prostaglandin synthesis.
Celecoxib is excreted in rat milk. Fetal toxicity was observed in peri-post natal studies in rats.
Conventional genotoxicity or carcinogenicity studies have revealed no special hazards for humans beyond those described in other sections of the Summary of Product Characteristics. In a two-year toxicity study in male rats at high doses it was observed an increase in thrombosis in tissues other than the adrenal gland.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
The 100 mg capsules contain lactose monohydrate, sodium lauryl sulfate, povidone K30, croscarmellose sodium and magnesium stearate. Capsule shells contain: gelatin, titanium dioxide E171; The ink contains indigo carmine E132, shellac, propylene glycol.
The 200 mg capsules contain lactose monohydrate, sodium lauryl sulfate, povidone K30, croscarmellose sodium and magnesium stearate. Capsule shells contain: gelatin, titanium dioxide E171; The ink contains yellow iron oxide E172, shellac, propylene glycol.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Do not store above 30 ° C.
06.5 Nature of the immediate packaging and contents of the package
Transparent or opaque PVC blister or heat-sealed aluminum blister.
Cartons of 2 cps, 5 cps, 6 cps, 10 cps, 20 cps, 30 cps, 40 cps, 50 cps, 60 cps, 100 cps, 10 x 10 cps, 10 x 30 cps, 10 x 50 cps, 1 x 50 cps in separable units, 1 x 100 cps in separable units, 5 x (10 x 10) cps.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Italia S.r.l.
Via Isonzo, 71 - 04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
Celebrex 100 mg
Blister packs Aluminum / transparent PVC
2 hard capsules 100 mg - AIC n. 034624015 / M
6 hard capsules 100 mg - AIC n. 034624027 / M
10 hard capsules 100 mg - AIC n. 034624039 / M
20 hard capsules 100 mg - AIC n. 034624041 / M
30 hard capsules 100 mg - AIC n. 034624054 / M
40 hard capsules 100 mg - AIC n. 034624066 / M
50 hard capsules 100 mg - AIC n. 034624078 / M
60 hard capsules 100 mg - AIC n. 034624080 / M
100 hard capsules 100 mg - AIC n. 034624092 / M
10 x 10 hard capsules 100 mg - AIC n. 034624104 / M
10 x 30 hard capsules 100 mg - AIC n. 034624116 / M
10 x 50 hard capsules 100 mg - AIC n. 034624128 / M
1 x 50 hard capsules 100 mg in separable units - AIC n. 034624130 / M
1 x 100 hard capsules 100 mg in separable units - AIC n. 034624142 / M
Blister packs Aluminum / opaque PVC
2 hard capsules 100 mg - AIC n. 034624155 / M
6 hard capsules 100 mg - AIC n. 034624167 / M
10 hard capsules 100 mg - AIC n. 034624179 / M
20 hard capsules 100 mg - AIC n. 034624181 / M
30 hard capsules 100 mg - AIC n. 034624193 / M
40 hard capsules 100 mg - AIC n. 034624205 / M
50 hard capsules 100 mg - AIC n. 034624217 / M
60 hard capsules 100 mg - AIC n. 034624229 / M
100 hard capsules 100 mg - AIC n. 034624231 / M
10 x 10 hard capsules 100 mg - AIC n. 034624243 / M
10 x 30 hard capsules 100 mg - AIC n. 034624256 / M
10 x 50 hard capsules 100 mg - AIC n. 034624268 / M
1 x 50 hard capsules 100 mg in separable units - AIC n. 034624270 / M
1 x 100 hard capsules 100 mg in separable units - AIC n. 034624282 / M
Aluminum / Aluminum blister packs
2 hard capsules 100 mg - AIC n. 034624294 / M
6 hard capsules 100 mg - AIC n. 034624306 / M
10 hard capsules 100 mg - AIC n. 034624318 / M
20 hard capsules 100 mg - AIC n. 034624320 / M
30 hard capsules 100 mg - AIC n. 034624332 / M
40 hard capsules 100 mg - AIC n. 034624344 / M
50 hard capsules 100 mg - AIC n. 034624357 / M
60 hard capsules 100 mg - AIC n. 034624369 / M
100 hard capsules 100 mg - AIC n. 034624371 / M
10 x 10 hard capsules 100 mg - AIC n. 034624383 / M
10 x 30 hard capsules 100 mg - AIC n. 034624395 / M
10 x 50 hard capsules 100 mg - AIC n. 034624407 / M
1 x 50 hard capsules 100 mg in separable units - AIC n. 034624419 / M
1 x 100 hard capsules 100 mg in separable units - AIC n. 034624421 / M
Celebrex 200 mg
Blister packs Aluminum / transparent PVC
2 hard capsules 200 mg - AIC n. 034624433 / M
6 hard capsules 200 mg - AIC n. 034624445 / M
10 hard capsules 200 mg - AIC n. 034624458 / M
20 hard capsules 200 mg - AIC n. 034624460 / M
30 hard capsules 200 mg - AIC n. 034624472 / M
40 hard capsules 200 mg - AIC n. 034624484 / M
50 hard capsules 200 mg - AIC n. 034624496 / M
60 hard capsules 200 mg - AIC n. 034624508 / M
100 hard capsules 200 mg - AIC n. 034624510 / M
10 x 10 hard capsules 200 mg - AIC n. 034624522 / M
10 x 30 hard capsules 200 mg - AIC n. 034624534 / M
10 x 50 hard capsules 200 mg - AIC n. 034624546 / M
1 x 50 hard capsules 200 mg in separable units - AIC n. 034624559 / M
1 x 100 hard capsules 200 mg in separable units - AIC n. 034624561 / M
Blister packs Aluminum / opaque PVC
2 hard capsules 200 mg - AIC n. 034624573 / M
6 hard capsules 200 mg - AIC n. 034624585 / M
10 hard capsules 200 mg - AIC n. 034624597 / M
20 hard capsules 200 mg - AIC n. 034624609 / M
30 hard capsules 200 mg - AIC n. 034624611 / M
40 hard capsules 200 mg - AIC n. 034624623 / M
50 hard capsules 200 mg - AIC n. 034624635 / M
60 hard capsules 200 mg - AIC n. 034624647 / M
100 hard capsules 200 mg - AIC n. 034624650 / M
10 x 10 hard capsules 200 mg - AIC n. 034624662 / M
10 x 30 hard capsules 200 mg - AIC n. 034624674 / M
10 x 50 hard capsules 200 mg - AIC n. 034624686 / M
1 x 50 hard capsules 200 mg in separable units - AIC n. 034624698 / M
1 x 100 hard capsules 200 mg in separable units - AIC n. 034624700 / M
Aluminum / Aluminum blister packs
2 hard capsules 200 mg - AIC n. 034624712 / M
6 hard capsules 200 mg - AIC n. 034624724 / M
10 hard capsules 200 mg - AIC n. 034624736 / M
20 hard capsules 200 mg - AIC n. 034624748 / M
30 hard capsules 200 mg - AIC n. 034624751 / M
40 hard capsules 200 mg - AIC n. 034624763 / M
50 hard capsules 200 mg - AIC n. 034624775 / M
60 hard capsules 200 mg - AIC n. 034624787 / M
100 hard capsules 200 mg - AIC n. 034624799 / M
10 x 10 hard capsules 200 mg - AIC n. 034624801 / M
10 x 30 hard capsules 200 mg - AIC n. 034624813 / M
10 x 50 hard capsules 200 mg - AIC n. 034624825 / M
1 x 50 hard capsules 200 mg in separable units - AIC n. 034624837 / M
1 x 100 hard capsules 200 mg in separable units - AIC n. 034624849 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 4 August 2000
Date of last renewal: 3 December 2009
10.0 DATE OF REVISION OF THE TEXT
March 18, 2013
