Description of Xenobrex capsules
Xenobrex capsule is a non-steroidal antinfammatory and antirheumatic drug.
It contains Celecoxib as its active ingredient. It also contains other inactive ingredients called excipients in sufficient quantities.
Celecoxib inhibits cycloxygenase (COX-2) enzyme to exert its action.
Pharmacokinetics of Xenobrex capsules
1. Absorption
After swallowing, Celecoxib is well absorbed reaching peak plasma concentrations after approximately 23 hours.
Dosing with food (high fat meal) delays absorption by about 1 hour
2. Distribution
Plasma protein binding is about 97% at therapeutic plasma concentrations and the drug is not preferentially bound to erythrocytes
3. Biotransformation
Celecoxib metabolism is primarily mediated via cytochrome P450 2C9.
Three metabolites, inactive as COX 1 or COX-2 inhibitors, have been identified in human plasma, that is, a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate.
Cytochrome P450 209 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity, such as those homozygous for the CYP2C3 polymorphism.
There is little experience of celecoxib in renal impairment. The pharmacokinetics of celecoxib has not been studied in patients with renal impairment but is unlikely to be markedly changed in these patients.
Thus caution is advised when treating patients with renal impairment.
Severe renal impairment is contraindicated
4. Elimination
Celecoxib is mainly eliminated by metabolism. Less than 1% of the dose is excreted unchanged in urine. The inter- subject variability in the exposure of celecoxib is about 10 fold.
Celecoxib exhibits dose- and time-independent pharmacokinetics in the therapeutic dose range.
Elimination half-life is 8-12 hours. Steady state plasma concentrations are reached within 5 days of treatment.
Uses of Xenobrex capsules
Xenobrex is indicated for the symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults.
Dosage of Xenobrex capsules
1. Dosage of Xenobrex capsules in Osteoarthritis
The usual recommended daily dose is 200 mg taken once daily or in two divided doses. In some patients with insufficient relief from symptoms, an increased dose of 200 mg twice daily may increase efficacy.
In the absence of an increase in therapeutic benefit after two weeks, other therapeutic options should be considered.
2. Dosage of Xenobrex capsules in Rheumatoid arthritis:
The initial recommended daily dose is 200 mg taken in two divided doses.
The dose may, if needed, later be increased to 200 mg twice daily.
In the absence of an increase in therapeutic benefit after two weeks, other therapeutic options should be considered
3. Dosage of Xenobrex capsules in Ankylosing spondylitis
The recommended daily dose of this product for the treatment of ankylosing spondylitis is 200mg taken once daily or in two divided doses.
In a few patients, with insufficient relief from symptoms, an increased dose of 400mg once daily or in two divided doses may increase efficacy.
In the absence of an increase in therapeutic benefit after two weeks, other therapeutic options should be considered.
The use of Xenobrex in special populations
1. Older people (> 65 years)
- As in younger adults, 200 mg per day should be used initially. The dose may, if needed, later be increased to 200 mg twice daily
2. Paediatric population
Celecoxib is not indicated for use in children.
3. CYP2CS Poor Metabolisers
Patients who are known or suspected to be CYP2C9 poor metabolisers, based on genotyping or previous history experience with other CYP2C9 substrates, should be administered celecoxib with caution as the risk of dose-dependent adverse effects is increased.
Consider reducing the dose to half the lowest recommended dose.
4. Hepatic impaired patients
Treatment should be initiated at half the recommended dose in patients with established moderate liver impairment with a serum albumin of 25-35 g/l. Experience in such patients is limited to cirrhotic patients.
5. Renal impaired patients
Experience with celecoxib in patients with mild or moderate renal impairment is limited; therefore such patients should be treated with caution.
Method of administration of Xenobrex capsules
Oral use
Celecoxib may be taken with or without food
Warning and precaution
Upper gastrointestinal complications [perforations, ulcers or bleedings (PUBS)], some of them resulting in fatal outcome, have occurred in patients treated with celecoxib.
Caution is advised with treatment of patients most at risk of developing a gastrointestinal complication with NSAIDs. These set of patients include:
- the elderly patients using any other NSAID or acetylsalicylic acid concomitantly
- patients with a prior history of gastrointestinal disease, such as ulceration and GI bleeding
There is further increase in the risk of gastrointestinal adverse effects for celecoxib (gastrointestinal ulceration or other gastrointestinal complications), when celecoxib is taken concomitantly with acetylsalicylic acid (even at low dose).
A significant difference in gastrointestinal safety between selective COX-2 inhibitors plus acetylsalicylic acid Vs NSAIDs plus acetylsalicylic acid has not been demonstrated in long-term clinical trials.
The concomitant use of celecoxib and a non aspirin NSAIDs should be avoided.
Contraindication of Xenobrex capsules
- This product should not be used on patients with history of hypersensitivity to the active substance or to any of the excipients.
- It should not be equally used in patients who are hypersensitive to sulphonamides.
- Patients with active peptic ulceration or gastrointestinal bleeding should avoid using celecoxib
- Celecoxib is contraindicated in patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic type reaction after taking acetylsalicylic acid or NSAIDs, including COX-2 inhibitors.
- Celecoxib is also contraindicated in pregnancy and in women of childbearing potential unless they are using effective method of contraception. Celecoxib has been shown to cause malformations in two animal species studied. The potential for human risk in pregnancy is unknown but cannot be excluded.
- Severe hepatic dysfunction (serum albumin < 25g/l or Child-Pugh score of ≥ 10)
- It is also contraindicated in patients with estimated creatinine clearance of less than 30 ml per minute.
- Patients with inflammatory bowel disease should not be placed on celecoxib
- It is not be used in patients with congestive heart failure
- Do not use celecoxib if you have an established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease
Side effects of Xenobrex capsules
The following are some side effects you may experience while on celecoxib:
- Cough
- Fever
- Skin rash
- Sneezing
- Sore throat
- Swelling of the face, fingers, feet, or lower legs
- Anemia
- Hyperkalemia
- Anxiety
- Depression
- Tiredness
- Constipation
- Eructation
- Gastritis
- Stomatitis
- Abnormal hepatic function
Less common or rare side effects are
- Abnormal growth in the breast
- Arm, back, or jaw pain
- Bloody or black, tarry stools
- Blurred vision
- Burning feeling in the chest or stomach
- Burning or stinging of the skin
- Burning tingling, numbness, or pain in the hands, arms, feet, or legs
- Chest pain or discomfort
- Chest tightness of heaviness
Overdose
There is no clinical experience of overdose.
Single doses up to 1200 mg and multiple doses up to 1200 mg twice daily have been administered to healthy subjects for nine days without clinically significant adverse effects.
In the event of suspected overdose, appropriate supportive medical care should be provided: e.g. by eliminating the gastric contents, clinical supervision and if necessary, the institution of symptomatic treatment.
Dialysis is unlikely to be an efficient method of drug removal due to high protein binding.
How to store Xenobrex capsules
Store in cool, dry place below 30ºC. Protect from direct sunlight. Keep all medicines out of reach of children