Celecoxib

Registered South African indications:

• Symptomatic treatment of inflammation and pain in osteoarthritis and rheumatoid arthritis
• Pain post dental surgery
• Post-operative pain - mild to moderate
• Musculoskeletal pain - mild to moderate
• Primary dysmenorrhoea - mild to moderate
• Relief of signs and symptoms of ankylosing spondylitis

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

Contraindications

South African recommendations

• Hypersensitivity to celecoxib or to any of the excipients
• Known sulphonamide hypersensitivity
• Pregnancy
• In women of childbearing potential unless using an effective method of contraception
• Severe hepatic impairment
• Severe renal impairment
• 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
• Established ischaemic heart disease and/or cerebrovascular disease (stroke)
• Peripheral arterial disease
• Peri-operative analgesia in the setting of coronary artery bypass surgery (CABG)

Recommendations in other jurisdictions

• Hypersensitivity to the active ingredient or any or its excipients
• Known hypersensitivity to sulfonamides
• Pregnancy
• Breastfeeding
• In women of childbearing potential unless using an effective method of contraception
• Patients with estimated creatinine clearance <30ml/min
• Severe hepatic dysfunction (serum albumin <25g/l or Child-Pugh score≥10)
• 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
• Inflammatory bowel disease
• Congestive heart failure (NYHA II-IV)
• Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease

Cautions

• Breastfeeding (South African recommendations)
• Mild to moderate renal impairment
• Moderate hepatic impairment
• Elderly
• Debilitated patients  
• History of gastrointestinal disease
• Hypertension
• Hyperlipidaemia
• Diabetes mellitus
• Left ventricular dysfunction
• Oedema
• Hypovolaemia
• Dehydration
• Fever and other signs of inflammation
• Alcohol use
• Smoker
• Poor CYP2C9 metabolisers
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• Patients on oral anticoagulants (like warfarin)

Forms avail. in SA and covered in this monograph: cap

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Osteoarthritis
- Symptomatic treatment of inflammation and pain

• Oral (cap): 200mg/day, as a single dose or two divided doses; Max: 400mg/24hrs

Rheumatoid arthritis
- Symptomatic treatment of inflammation and pain

• Oral (cap): 100-200mg, twice dly

Pain post dental surgery

• Oral (cap): 100-200mg, not less than 4-hour intervals; Max: 400mg/24hrs

Post-operative pain - mild to moderate

• Oral (cap): 200mg, once dly; Additional dose: 200mg, if needed

Musculoskeletal pain - mild to moderate

• Oral (cap): 200mg, twice dly

Primary dysmenorrhoea – mild to moderate

• Oral (cap): Initial: 400mg, then an additional dose of 200mg if needed on the first day; Then: 200mg, twice dly on subsequent days

Relief of signs and symptoms ankylosing spondylitis

• Oral (cap): 200mg/day as a single dose OR 100mg, twice dly; Some patients may benefit from total daily dose of 400mg

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Celecoxib can be taken with or without food

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The shortest duration possible and the lowest effective daily dose should be used due to the cardiovascular risks of celecoxib that may increase with dose and duration of exposure

Not established for use children below 18 years

Pregnancy

South African recommendations

• Contraindicated
• Celecoxib has been shown to cause malformations in the animal species studied. The potential for human risk in pregnancy is unknown but cannot be excluded
• 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, 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 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
• Celecoxib is contraindicated in women of childbearing potential unless using an effective method of contraception

Recommendations in other jurisdictions

• Contraindicated
• Celecoxib is contraindicated in pregnancy and in women of childbearing potential unless using an effective method of contraception. Celecoxib has been shown to cause malformations in the two animal species studied. The potential for human risk in pregnancy is unknown, but cannot be excluded
• Studies in animals (rats and rabbits) have shown reproductive toxicity, including malformations. 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 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 upon discontinuation
• Celecoxib is contraindicated in pregnancy and in women who can become pregnant. If a woman becomes pregnant during treatment, celecoxib should be discontinued

Breastfeeding

South African recommendations

• Caution; not recommended
• Celecoxinb is excreted in the milk of lactating rats at concentrations similar to those in plasma. Limited data indicate that celecoxib is excreted in breast milk and therefore should not be used during lactation

Recommendations in other jurisdictions

• Contraindicated
• Celecoxib is excreted in the milk of lactating rats at concentrations similar to those in plasma. Administration of celecoxib to a limited number of breastfeeding women has shown a very low transfer of celecoxib into breast milk. Women who take celecoxib 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

Renal Impairment

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Contraindicated

Hepatic Impairment

• Mild: No dose adjustment recommended
• Moderate: Caution; dose adjustment recommended
  Reduce dose by 50%
• Severe: Contraindicated

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Hypertonia
• Headache
• Cerebral infarction
• Paraesthesia
• Somnolence
• Ataxia
• Dysgeusia
• Intracranial haemorrhage
• Aseptic meningitis
• Epilepsy
• Ageusia
• Anosmia
• Insomnia
• Anxiety
• Depression
• Fatigue
• Confusional state
• Hallucinations

Cardiovascular Disorders

• Myocardial infarction
• Cardiac failure
• Palpitations
• Tachycardia
• Arrhythmia
• Hypertension
• Pulmonary embolism
• Flushing
• Vasculitis

Respiratory Disorders

• Rhinitis
• Cough
• Dyspnoea
• Bronchospasm
• Pneumonitis
• Sinusitis
• Upper respiratory tract infection
• Pharyngitis

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain
• Diarrhoea
• Dyspepsia
• Flatulence
• Dysphagia
• Constipation
• Gastritis
• Stomatitis
• Gastrointestinal inflammation
• Eructation
• Gastro-intestinal haemorrhage
• Duodenal ulcer
• Gastric ulcer
• Oesophageal ulcer
• Intestinal ulcer 
• Intestinal perforation
• Oesophagitis
• Melaena
• Pancreatitis
• Colitis  

Hepatobiliary Disorders

• Abnormal hepatic function
• Hepatitis
• Hepatic failure 
• Cholestasis
• Jaundice

Genitourinary Disorders

• Increased serum creatinine
• Increased serum urea
• Acute kidney injury
• Hyponatraemia
• Tubulointerstitial nephritis
• Nephrotic syndrome
• Glomerulonephritis
• Menstrual disorder
• Infertility
• Urinary tract infection  

Endocrine and Metabolic Disorders

• Hyperkalaemia

Musculoskeletal Disorders

• Arthralgia
• Muscle spasms
• Myositis

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus 
• Urticaria
• Ecchymosis
• Angioedema
• Alopecia
• Photo-sensitivity
• Dermatitis exfoliative
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Drug reaction with eosinophilia and systemic symptoms
• Acute generalised exanthematous pustulosis
• Dermatitis bullous

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Leukopenia
• Thrombocytopenia
• Pancytopenia
• Hypersensitivity
• Anaphylactic shock
• Anaphylactic reaction  

Sensory Disorders

• Vision blurred
• Conjunctivitis
• Eye haemorrhage
• Retinal artery occlusion
• Retinal vein occlusion
• Tinnitus
• Hypoacusis

• Oral anticoagulants
• Angiotensin-converting enzyme inhibitors
• Angiotensin II receptor antagonists
• Diuretics
• Ciclosporin
• Tacrolimus
• Aspirin
• CYP2D6 substrates
• CYP2C19 substrates
• Methotrexate
• Lithium
• Oral contraceptives
• CYP2C9 inhibitors
• CYP2C9 inducers  

None routine. Specific cases may require

• Renal function
• Hepatic function
• Blood pressure

• The decision to prescribe a COX-2 inhibitor should be based on an assessment of the individual patient's overall risks
• 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
• Celecoxib may mask fever and other signs and symptoms of inflammation
• Celecoxib may be taken with or without food

Inhibits prostaglandin synthesis by selective inhibition of cyclooxygenase-2.

Capsule 100mg 

• Anabrex 100 (Trinity Pharma)
• Celebrex (UpJohn) originator
• Celecoxib Unicorn (Sandoz)
• Colcibra 100 (Ranbaxy Pharmaceuticals)
• Coxep 100mg (Pharma Dynamics)
• Coxleon 100 (Sandoz)
• Cyretib 100 (Trinity Pharma)

Capsule 200mg 

• Anabrex 200 (Trinity Pharma)
• Celebrex (Pfizer) originator
• Celecoxib Unicorn (Sandoz)
• Colcibra 200 (Ranbaxy Pharmaceuticals)
• Coxep 200mg (Pharma Dynamics)
• Coxleon 200 (Sandoz)
• Cyretib 200 (Trinity Pharma)