Celecoxib Pfizer 100 mg. 200 mg Hard capsules

u2022 Symptomatic treatment of inflammation and pain in osteoarthritis and rheumatoid arthritis.

u2022 Treatment of pain post dental surgery.

u2022 Treatment of mild to moderate post-operative pain.

u2022 Treatment of mild to moderate musculoskeletal pain.

u2022 Treatment of mild to moderate primary dysmenorrhoea.

u2022 Relief of signs and symptoms of ankylosing spondylitis.

As the cardiovascular risks of CELECOXIB PFIZER may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used.

Posology

Osteoarthritis

The recommended daily dose is 200 mg, administered as a single dose or as two divided doses. Doses up to 400 mg per day have been studied.

Rheumatoid arthritis

The recommended daily dose is 100 mg or 200 mg twice per day.

Pain post dental surgery

The recommended dose is 100 mg to 200 mg, up to a maximum daily dose of 400 mg. Dosing intervals should not be less than 4 hours.

Mild to moderate post-operative pain

The recommended dose is 200 mg once daily. Some patients may benefit from an additional 200 mg dose.

Mild to moderate musculoskeletal pain

The recommended dose is 200 mg twice daily.

Mild to moderate primary dysmenorrhoea

The recommended dose is 400 mg initially, followed by an additional 200 mg dose if needed on the first day. On subsequent days, the recommended dose is 200 mg twice daily.

Ankylosing spondylitis

The recommended daily dose is 200 mg, administered as a single dose or as 100 mg twice per day. Some patients may benefit from a total daily dose of 400 mg.

Special populations

Elderly

No dosage adjustment is necessary. However, for elderly patients with a lower than average body weight (50 kg), it is advisable to initiate therapy at the lowest recommended dose.

Hepatic impairment

No dosage adjustment is necessary in patients with mild hepatic impairment. Introduce CELECOXIB PFIZER at half the recommended dose in patients with moderate hepatic impairment. For pain post dental surgery, introduce CELECOXIB PFIZER at the lowest recommended dose. There is no clinical experience in patients with severe hepatic impairment (see section 4.3).

Renal impairment

No dosage adjustment is necessary in patients with mild or moderate renal impairment. There is no clinical experience in patients with severe renal impairment (see section 4.3).

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 PFIZER 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).

Paediatric population

CELECOXIB PFIZER has not been studied in subjects under 18 years old.

Method of administration

For oral use. CELECOXIB PFIZER may be taken with or without food.

u2022 Hypersensitivity to celecoxib or to any of the excipients of CELECOXIB PFIZER (listed in section 6.1).

u2022 Known sulphonamide hypersensitivity.

u2022 Severe impairment of hepatic function.

u2022 Severe impairment of renal function.

u2022 Asthma, urticaria or allergic-type reactions precipitated by aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), including other cyclooxygenase 2 (COX-2) specific inhibitors.

u2022 Established ischaemic heart disease and/or cerebrovascular disease (stroke) and peripheral arterial disease.

u2022 Peri-operative analgesia in the setting of coronary artery bypass surgery (CABG).

u2022 Pregnancy.

u2022 In women of childbearing potential unless using an effective method of contraception (see section 4.6). CELECOXIB PFIZER has been shown to cause malformations in the animal species studied (see section 4.6). The potential for human risk in pregnancy is unknown but cannot be excluded.

CELECOXIB PFIZER may predispose to cardiovascular events, cerebrovascular events, gastrointestinal events or cutaneous reactions which may be fatal.

Safety and efficacy of CELECOXIB PFIZER have not been established for treatment exceeding 12 weeks in osteoarthritis and 24 weeks in rheumatoid arthritis.

Cardiovascular effects

There is insufficient data to assess cardiovascular safety beyond one year of continuous treatment. CELECOXIB PFIZER may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal. There appears to be a higher risk for cardiovascular events with higher doses and longer duration of treatment. The shortest duration possible and the lowest effective dose should be used. Caution is advised when CELECOXIB PFIZER is prescribed to patients with cardiovascular risk factors e.g. hypertension, diabetes, smoking and hypercholesterolaemia. Medical practitioners and patients should remain alert for the development of such events, even in the absence of previous cardiovascular symptoms. Because of its lack of platelet effects, CELECOXIB PFIZER is not a substitute for aspirin for cardiovascular prophylaxis. Therefore, antiplatelet therapies should not be discontinued.

Hypertension

As with all NSAIDs, CELECOXIB PFIZER 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. Blood pressure should be monitored closely during the initiation of therapy with CELECOXIB PFIZER and throughout the course of therapy.

Gastrointestinal (GI) effects

Upper and lower gastrointestinal perforations, ulcers or bleeds have occurred in patients treated with CELECOXIB PFIZER. Patients most at risk of developing these types of GI complications with NSAIDs are the elderly, patients with cardiovascular disease, patients using concomitant glucocorticoids, antiplatelet medicines (such as aspirin), or other NSAIDs, patients using alcohol or patients with a prior history of, or active, gastrointestinal disease, such as ulceration, GI bleeding or inflammatory conditions. Most spontaneous reports of fatal gastrointestinal events have been in elderly or debilitated patients.

Serious skin 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 PFIZER. Patients appear to be at highest risk for these events early in the course of therapy: the onset of the event occurring in the majority of cases within the first month of treatment. Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) has been reported in patients receiving CELECOXIB PFIZER. CELECOXIB PFIZER should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as CELECOXIB PFIZER. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, haematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue CELECOXIB PFIZER and evaluate the patient immediately.

Celecoxib contains a sulphonamide moiety. In clinical trials CELECOXIB PFIZER did not induce bronchospasm in patients with asthma. However, CELECOXIB PFIZER has not been evaluated in patients in whom attacks of asthma, urticaria or acute rhinitis have been precipitated by aspirin or NSAIDs. Use in such patients should be avoided until further information is available.

Fluid retention and oedema

As with other medicines known to inhibit prostaglandin synthesis, fluid retention and oedema have been observed in patients taking CELECOXIB PFIZER, therefore CELECOXIB PFIZER should be used with caution in patients with compromised cardiac function, pre-existing oedema and other conditions predisposing to, or worsened by, fluid retention. Patients with pre-existing congestive heart failure or hypertension should be closely monitored.

Renal effects

NSAIDs, including CELECOXIB PFIZER may cause renal toxicity. Clinical trials with CELECOXIB PFIZER 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, and the elderly. Such patients should be carefully monitored while receiving treatment with CELECOXIB PFIZER. Caution should be used when initiating treatment in patients with dehydration. It is advisable to rehydrate patients first and then start therapy with CELECOXIB PFIZER. Renal function should be closely monitored in patients with advanced renal disease who are administered CELECOXIB PFIZER.

Hepatic effects

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 PFIZER. A patient with symptoms and/or signs of liver dysfunction, or in whom an abnormal liver function test has occurred, should be monitored carefully for evidence of the development of a more severe hepatic reaction while on therapy with CELECOXIB PFIZER.

CYP2D6 inhibition

CELECOXIB PFIZER inhibits CYP2D6. Although it is not a strong inhibitor of this enzyme, a dose reduction may be necessary for individually dose-titrated medicines that are metabolised by CYP2D6 (see section 4.5).

Anaphylactoid reactions

As with NSAIDs in general, anaphylactoid reactions have occurred in patients exposed to CELECOXIB PFIZER (see section 4.3).

General

By reducing inflammation, CELECOXIB PFIZER may diminish the utility of diagnostic signs, such as fever, in detecting infections. The concomitant use of CELECOXIB PFIZER and a non-aspirin NSAID should be avoided.

Use with oral anticoagulants

In patients on concurrent therapy with warfarin or similar medicines, serious bleeding events, some of them fatal, have been reported. Because increases in prothrombin time (INR) have been reported, anticoagulant activity should be monitored in patients receiving warfarin/coumarin-type oral anticoagulants after initiating treatment with CELECOXIB PFIZER or changing the dose. Concomitant use of anticoagulants with NSAIDs may increase the risk of bleeding. Caution should be exercised when combining CELECOXIB PFIZER with warfarin or other oral anticoagulants including novel anticoagulants (e.g. apixaban, dabigatran and rivaroxaban).

Lactose intolerance

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

General

CELECOXIB PFIZER metabolism is predominantly mediated via cytochrome P450 (CYP) 2C9 in the liver. Co-administration of CELECOXIB PFIZER with medicines that are known to inhibit CYP2C9 should be done with caution.

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

In vitro studies indicate that celecoxib, although not a substrate, is an inhibitor of CYP2D6. Therefore, there is a potential for an in vivo medicine interaction with medicines that are metabolised by CYP2D6.

Anti-hypertensives

Inhibition of prostaglandins may diminish the effect of anti-hypertensive medicines including angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, diuretics and beta-blockers. The risk of acute renal insufficiency, which is usually reversible, may be increased in some patients with compromised renal function (e.g. patients on diuretics or elderly patients) when ACE-inhibitors, angiotensin II receptor antagonists and/or diuretics are combined with NSAIDs, including CELECOXIB PFIZER. 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 PFIZER 200 mg twice daily 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 PFIZER 200 mg twice daily, 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.

Aspirin

CELECOXIB PFIZER can be used with low dose aspirin. However, concomitant administration of aspirin with CELECOXIB PFIZER may result in an increased rate of GI ulceration or other complications, compared to use of CELECOXIB PFIZER alone. Because of its lack of platelet effects, CELECOXIB PFIZER is not a substitute for aspirin for cardiovascular prophylaxis. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thromboembolic events associated with CELECOXIB PFIZER.

Ciclosporin

Co-administration of NSAIDs and ciclosporin may increase the nephrotoxic effect of ciclosporin.

Fluconazole

Concomitant administration of fluconazole at 200 mg once daily resulted in a two-fold increase in CELECOXIB PFIZER plasma concentration. This increase is due to the inhibition of CELECOXIB PFIZER metabolism via CYP2C9 by fluconazole. CELECOXIB PFIZER should be introduced at half the recommended dose in patients receiving the CYP2C9 inhibitor fluconazole.

Dextromethorphan and metoprolol

Concomitant administration of CELECOXIB PFIZER 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 PFIZER inhibition of the CYP2D6 substrate metabolism.

Diuretics

Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.

Glibenclamide

CELECOXIB PFIZER does not affect the pharmacokinetics of glibenclamide to a clinically relevant extent.

Ketoconazole and antacids

Ketoconazole or antacids have not been observed to affect the pharmacokinetics of CELECOXIB PFIZER.

Lithium

In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17 % in subjects receiving lithium 450 mg twice daily with CELECOXIB PFIZER 200 mg twice daily as compared to subjects receiving lithium alone. Patients on lithium treatment should be closely monitored when CELECOXIB PFIZER is introduced or withdrawn.

Methotrexate

In an interaction study of rheumatoid arthritis patients taking methotrexate, CELECOXIB PFIZER did not have a significant effect on the pharmacokinetics of methotrexate.

Other medicines

In specific studies in healthy volunteers with other medicines metabolised by CYP2C9, CELECOXIB PFIZER was found to produce no clinically significant pharmacokinetic interaction with phenytoin or tolbutamide.

Oral contraceptives

In an interaction study, CELECOXIB PFIZER had no clinically relevant effects on the pharmacokinetics of a prototype combination oral contraceptive (1 mg norethindrone/0,035 mg ethinyl estradiol).

Warfarin

In patients on concurrent therapy with warfarin, increases in prothrombin time (INR) have been reported (see section 4.4).

Fertility

Based on the mechanism of action, the use of NSAIDs, including CELECOXIB PFIZER, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women.

Pregnancy

Studies in animals have shown reproductive toxicity. 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. CELECOXIB PFIZER, as with other medicines inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus and should be avoided during pregnancy. During the second or third trimester of pregnancy, NSAIDs including CELECOXIB PFIZER may cause foetal 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.

Breastfeeding

CELECOXIB PFIZER is excreted in the milk of lactating rats at concentrations similar to those in plasma. Limited data indicate that CELECOXIB PFIZER is excreted in breast milk and therefore should not be used during lactation.

The effect of CELECOXIB PFIZER on ability to drive or use machinery has not been studied but based on its pharmacodynamic properties and overall safety profile it is unlikely to have an effect.

Tabulated summary of adverse reactions

The following side effects have been reported in patients on CELECOXIB PFIZER treatment. Incidence rates are categorised as follows: Very common (u2265 1/10); common (u2265 1/100 to < 1/10); uncommon (u2265 1/1 000 to < 1/100); rare (u2265 1/10 000 to < 1/1 000); very rare (< 1/10 000).

MedDRA System Organ Class Frequency Undesirable effects

Infections and infestations Common Bronchitis, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection urinary tract infection

Blood and lymphatic system disorders Uncommon Anaemia, thrombocytopenia

Immune system disorders Common Allergy aggravated

Uncommon Hypersensitivity

Rare Angioedema

Psychiatric disorders Common Insomnia

Uncommon Anxiety

Rare Confusion

Nervous system disorders Common Dizziness, hypertonia

Uncommon Somnolence

Eye disorders Uncommon Blurred vision

Ear and labyrinth disorders Uncommon Tinnitus

Cardiac disorders Uncommon Arrhythmia, palpitations, tachycardia

Rare Congestive heart failure

Vascular disorders Common Hypertension (including aggravated hypertension)

Uncommon Flushing

Respiratory, thoracic and mediastinal disorders Common Cough

Gastrointestinal disorders Common Vomiting, abdominal pain, diarrhoea, dyspepsia, flatulence, tooth disorder

Uncommon Gastric ulcer

Rare Pancreatitis, duodenal ulcer, oesophageal ulcer, intestinal perforation

Hepatobiliary disorders Uncommon Increased hepatic enzyme (including increased SGOT and SGPT)

Skin and subcutaneous tissue disorders Common Rash, pruritus

Uncommon Alopecia, urticaria, ecchymosis

Rare Angioedema, bullous dermatitis

General disorders and administration site conditions Common Peripheral oedema, influenza-like illness

Uncommon Face oedema

Injury, poisoning and procedural complications Common Accidental injury

Post-marketing experience

Reactions from post-marketing experience include the following:

MedDRA System Organ Class Undesirable effects

Immune system disorders Anaphylactic reaction

Psychiatric disorders Hallucination

Nervous system disorders Intracranial haemorrhage, ageusia, anosmia, aseptic meningitis, cerebrovascular incident (stroke)

Eye disorders Conjunctivitis

Cardiac disorders Myocardial infarction, cardiovascular thrombotic events

Vascular disorders Vasculitis

Respiratory, thoracic and mediastinal disorders Pulmonary embolism, pneumonitis

Gastrointestinal disorders Gastrointestinal haemorrhage

Hepatobiliary disorders Hepatitis, hepatic failure, fulminant hepatitis, hepatic necrosis, cholestasis, cholestatic hepatitis, jaundice

Skin and subcutaneous tissue disorders Photosensitivity reaction, skin exfoliation (including erythema multiforme and Stevens-Johnson syndrome), toxic epidermal necrolysis, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) (see section 4.4), acute generalised exanthematous pustulosis (AGEP), exfoliative dermatitis

Renal and urinary disorders Acute renal failure, tubulointerstitial nephritis, hyponatraemia, nephrotic syndrome, glomerulonephritis minimal lesion

Reproductive system and breast disorders Menstrual disorder, female infertility (decreased female fertility)

General disorders and administration site conditions Chest pain

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

There is no clinical experience of overdose. Single doses up to 1 200 mg and multiple doses up to 1 200 mg twice daily have been administered to healthy subjects without clinically significant adverse effects. In the event of suspected overdose, appropriate supportive medical care should be provided. Dialysis is unlikely to be an efficient method of medicine removal.