CORREX is indicated in adults and adolescents 16 years of age and older for the symptomatic
relief of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and the pain and 
signs of inflammation associated with acute gouty arthritis.
CORREX is indicated in adults and adolescents 16 years of age and older for the short-term 
treatment of moderate pain associated with dental surgery.
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, 4.4).
 

Posology
As the cardiovascular risks of etoricoxib may increase with dose and duration of exposure, the 
shortest duration possible and the lowest effective daily dose should be used. The patient's need 
for symptomatic relief and response to therapy should be re-evaluated periodically, especially in
patients with osteoarthritis (see sections 4.3, 4.4, 4.8 and 5.1).
Osteoarthritis
The recommended dose is 30 mg once daily. In some patients with insufficient relief from symptoms, 
an increased dose of 60 mg once daily may increase efficacy. In the absence of an increase in 
therapeutic benefit, other therapeutic options should be considered.
Rheumatoid arthritis
The recommended dose is 60 mg once daily. In some patients with insufficient relief from symptoms, 
an increased dose of 90 mg once daily may increase efficacy. Once the patient is

clinically stabilised, down-titration to a 60 mg once daily dose may be appropriate. In the absence
of an increase in therapeutic benefit, other therapeutic options should be considered.
Ankylosing spondylitis
The recommended dose is 60 mg once daily. In some patients with insufficient relief from symptoms, 
an increased dose of 90 mg once daily may increase efficacy. Once the patient is clinically 
stabilised, down-titration to a 60 mg once daily dose may be appropriate. In the absence of an 
increase in therapeutic benefit, other therapeutic options should be considered.
Acute pain conditions
For acute pain conditions, etoricoxib should be used only for the acute symptomatic period.
Acute gouty arthritis
The recommended dose is 120 mg once daily. In clinical trials for acute gouty arthritis, etoricoxib 
was given for 8 days.
Postoperative dental surgery pain
The recommended dose is 90 mg once daily, limited to a maximum of 3 days. Some patients may require 
other postoperative analgesia in addition to CORREX during the three day treatment period.
Doses greater than those recommended for each indication have either not demonstrated additional 
efficacy or have not been studied. Therefore:
The dose for OA should not exceed 60 mg daily.
The dose for RA and ankylosing spondylitis should not exceed 90 mg daily.
The dose for acute gout should not exceed 120 mg daily, limited to a maximum of 8 days treatment.
The dose for postoperative acute dental surgery pain should not exceed 90 mg daily, limited to a 
maximum of 3 days.
Special populations
Elderly patients
No dosage adjustment is necessary for elderly patients. As with other drugs, caution should be 
exercised in elderly patients (see section 4.4).
Patients with hepatic impairment
Regardless of indication, in patients with mild hepatic dysfunction (Child-Pugh score 5-6) a dose 
of 60 mg once daily should not be exceeded. In patients with moderate hepatic dysfunction 
(Child-Pugh score 7-9), regardless of indication, the dose of 30 mg once daily should not be 
exceeded.
Clinical experience is limited particularly in patients with moderate hepatic dysfunction and 
caution is advised. There is no clinical experience in patients with severe hepatic dysfunction 
(Child-Pugh score ≥10); therefore, its use is contra-indicated in these patients (see sections 4.3, 
4.4 and 5.2).
Patients with renal impairment
No dosage adjustment is necessary for patients with creatinine clearance ≥30 ml/min (see section 
5.2). The use of etoricoxib in patients with creatinine clearance <30 ml/min is contra-indicated  
(see sections 4.3 and 4.4).
Paediatric population
Etoricoxib is contra-indicated in children and adolescents under 16 years of age (see section 4.3). 
Method of administration
CORREX is administered orally and may be taken with or without food. The onset of the effect of the 
medicinal product may be faster when CORREX is administered without food. This should be
considered when rapid symptomatic relief is needed.
 

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Active peptic ulceration or active gastro-intestinal (GI) bleeding. • Patients who, after taking acetylsalicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors, experience bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions. • Pregnancy and lactation (see sections 4.6 and 5.3). • Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10). • Estimated renal creatinine clearance <30 ml/min. • Children and adolescents under 16 years of age. • Inflammatory bowel disease. • Congestive heart failure (NYHA II-IV). • Patients with hypertension whose blood pressure is persistently elevated above 140/90 mmHg and has not been adequately controlled. • Established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease.

Gastrointestinal effects
Upper gastrointestinal complications [perforations, ulcers or bleedings (PUBs)], some of them 
resulting in fatal outcome, have occurred in patients treated with etoricoxib.
Caution is advised with treatment of patients most at risk of developing a gastrointestinal 
complication with NSAIDs; the elderly, patients using any other NSAID or acetylsalicylic acid
concomitantly or patients with a prior history of gastrointestinal disease, such as ulceration and 
GI
bleeding.
There is a further increase in the risk of gastrointestinal adverse effects (gastrointestinal 
ulceration or other gastrointestinal complications) when etoricoxib is taken concomitantly with 
acetylsalicylic acid (even at low doses). A significant difference in GI safety between selective 
COX-2 inhibitors + acetylsalicylic acid vs. NSAIDs + acetylsalicylic acid has not been demonstrated 
in long-term clinical trials (see section 5.1).
Cardiovascular effects
Clinical trials suggest that the selective COX-2 inhibitor class of drugs may be associated with a
risk of thrombotic events (especially myocardial infarction (MI) and stroke), relative to placebo  
and some NSAIDs. As the cardiovascular risks of etoricoxib may increase with dose and duration of 
exposure, the shortest duration possible and the lowest effective daily dose should be used. The 
patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, 
especially in patients with osteoarthritis (see sections 4.2, 4.3, 4.8 and 5.1).
Patients with significant risk factors for cardiovascular events (e.g. hypertension, 
hyperlipidaemia, diabetes mellitus, smoking) should only be treated with etoricoxib after careful 
consideration (see section 5.1).
COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of 
cardiovascular thrombo-embolic diseases because of their lack of antiplatelet effect. Therefore 
antiplatelet therapies should not be discontinued (see sections above, 4.5 and 5.1.).
Renal effects
Renal prostaglandins may play a compensatory role in the maintenance of renal perfusion. Therefore, 
under conditions of compromised renal perfusion, administration of etoricoxib may cause a reduction 
in prostaglandin formation and, secondarily, in renal blood flow, and thereby impair renal 
function. Patients at greatest risk of this response are those with pre-existing significantly 
impaired renal function, uncompensated heart failure, or cirrhosis. Monitoring of renal function in 
such patients should be considered.
Fluid retention, oedema and hypertension
As with other medicinal products known to inhibit prostaglandin synthesis, fluid retention, oedema 
and hypertension have been observed in patients taking etoricoxib. All Nonsteroidal Anti- 
inflammatory Drugs (NSAIDs), including etoricoxib, can be associated with new onset or recurrent
congestive heart failure. For information regarding a dose related response for etoricoxib see
section 5.1. Caution should be exercised in patients with a history of cardiac failure, left
ventricular dysfunction, or hypertension and in patients with pre-existing oedema from any other 
reason. If there is clinical evidence of deterioration in the condition of these patients, 
appropriate
measures including discontinuation of etoricoxib should be taken.
Etoricoxib may be associated with more frequent and severe hypertension than some other NSAIDs and 
selective COX-2 inhibitors, particularly at high doses. Therefore, hypertension should be 
controlled before treatment with etoricoxib (see section 4.3) and special attention should be paid 
to blood pressure monitoring during treatment with etoricoxib. Blood pressure should be monitored 
within two weeks after initiation of treatment and periodically thereafter. If blood pressure rises 
significantly, alternative treatment should be considered.
Hepatic effects
Elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (approximately 
three or more times the upper limit of normal) have been reported in approximately 1% of patients 
in clinical trials treated for up to one year with etoricoxib 30, 60 and 90 mg daily.
Any patients with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver 
function test has occurred, should be monitored. If signs of hepatic insufficiency occur, or if 
persistently abnormal liver function tests (three times the upper limit of normal) are detected, 
etoricoxib should be discontinued.
General
If during treatment, patients deteriorate in any of the organ system functions described above, 
appropriate measures should be taken and discontinuation of etoricoxib therapy should be 
considered. Medically appropriate supervision should be maintained when using etoricoxib in the 
elderly and in patients with renal, hepatic, or cardiac dysfunction.
Caution should be used when initiating treatment with etoricoxib in patients with dehydration. It 
is advisable to rehydrate patients prior to starting therapy with etoricoxib.
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 NSAIDs and some selective COX-2 inhibitors during post-marketing surveillance (see section 
4.8). Patients appear to be at highest risk for these reactions early in the course of therapy with 
the onset of the reaction occurring in the majority of cases within the first month of
treatment. Serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been
reported in patients receiving etoricoxib (see section 4.8). Some selective COX-2 inhibitors have 
been associated with an increased risk of skin reactions in patients with a history of any drug 
allergy. Etoricoxib should be discontinued at the first appearance of skin rash, mucosal lesions, 
or any other sign of hypersensitivity.
Etoricoxib may mask fever and other signs of inflammation.
Caution should be exercised when co-administering etoricoxib with warfarin or other oral 
anticoagulants (see section 4.5).
The use of etoricoxib, as with any medicinal product known to inhibit cyclooxygenase / 
prostaglandin synthesis, is not recommended in women attempting to conceive (see sections 4.6, 5.1, 
and 5.3).
CORREX tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, 
the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
 

Pharmacodynamic interactions
Oral anticoagulants: In subjects stabilised on chronic warfarin therapy, the administration of
etoricoxib 120 mg daily was associated with an approximate 13% increase in prothrombin time 
International Normalised Ratio (INR). Therefore, patients receiving oral anticoagulants should be 
closely monitored for their prothrombin time INR, particularly in the first few days when therapy
with etoricoxib is initiated or the dose of etoricoxib is changed (see section 4.4).

Diuretics, ACE inhibitors and Angiotensin II Antagonists: NSAIDs may reduce the effect of
diuretics and other antihypertensive drugs. In some patients with compromised renal function
(e.g. dehydrated patients or elderly patients with compromised renal function) the co- 
administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclo- 
oxygenase may result in further deterioration of renal function, including possible acute renal 
failure, which is usually reversible. These interactions should be considered in patients taking 
etoricoxib concomitantly with ACE inhibitors or angiotensin II antagonists. 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.
Acetylsalicylic Acid: In a study in healthy subjects, at steady state, etoricoxib 120 mg once daily
had no effect on the anti-platelet activity of acetylsalicylic acid (81 mg once daily). Etoricoxib 
can be used concomitantly with acetylsalicylic acid at doses used for cardiovascular prophylaxis 
(low- dose acetylsalicylic acid). However, concomitant administration of low-dose acetylsalicylic 
acid with etoricoxib may result in an increased rate of GI ulceration or other complications 
compared  to use of etoricoxib alone. Concomitant administration of etoricoxib with doses of 
acetylsalicylic acid above those for cardiovascular prophylaxis or with other NSAIDs is not 
recommended (see sections 5.1 and 4.4.).
Cyclosporin and tacrolimus: Although this interaction has not been studied with etoricoxib, 
coadministration of cyclosporin or tacrolimus with any NSAID may increase the nephrotoxic effect of 
cyclosporin or tacrolimus. Renal function should be monitored when etoricoxib and either of these 
drugs is used in combination.
Pharmacokinetic interactions
The effect of etoricoxib on the pharmacokinetics of other drugs
Lithium: NSAIDs decrease lithium renal excretion and therefore increase lithium plasma levels. If 
necessary, monitor blood lithium closely and adjust the lithium dosage while the combination is 
being taken and when the NSAID is withdrawn.
Methotrexate: Two studies investigated the effects of etoricoxib 60, 90 or 120 mg administered
once daily for seven days in patients receiving once-weekly methotrexate doses of 7.5 to 20 mg for 
rheumatoid arthritis. Etoricoxib at 60 and 90 mg had no effect on methotrexate plasma 
concentrations or renal clearance. In one study, etoricoxib 120 mg had no effect, but in the other 
study, etoricoxib 120 mg increased methotrexate plasma concentrations by 28% and reduced renal 
clearance of methotrexate by 13%. Adequate monitoring for methotrexate-related toxicity is
recommended when etoricoxib and methotrexate are administered concomitantly.
Oral contraceptives: Etoricoxib 60 mg given concomitantly with an oral contraceptive containing
35 micrograms ethinyl estradiol (EE) and 0.5 to 1 mg norethindrone for 21 days increased the steady 
state AUC_0-24hr of EE by 37%. Etoricoxib 120 mg given with the same oral contraceptive 
concomitantly or separated by 12 hours, increased the steady state AUC_0-24hr of EE by 50 to 60%. 
This increase in EE concentration should be considered when selecting an oral contraceptive for use 
with etoricoxib. An increase in EE exposure can increase the incidence of adverse events associated 
with oral contraceptives (e.g., venous thrombo-embolic events in women at risk). Hormone 
Replacement Therapy (HRT): Administration of etoricoxib 120 mg with hormone
replacement therapy consisting of conjugated estrogens (0.625 mg PREMARINTM) for 28 days, increased 
the mean steady state AUC0-24hr of unconjugated estrone (41%), equilin (76%), and 17- β-estradiol 
(22%). The effect of the recommended chronic doses of etoricoxib (30, 60, and 90  mg) has not been 
studied. The effects of etoricoxib 120 mg on the exposure (AUC_0-24hr) to these estrogenic 
components of PREMARIN were less than half of those observed when PREMARIN was administered alone 
and the dose was increased from 0.625 to 1.25 mg. The clinical
significance of these increases is unknown, and higher doses of PREMARIN were not studied in
combination with etoricoxib. These increases in estrogenic concentration should be taken into 
consideration when selecting post-menopausal hormone therapy for use with etoricoxib because the increase in oestrogen exposure might increase the risk of adverse events associated with
HRT.
Prednisone/prednisolone: In drug-interaction studies, etoricoxib did not have clinically important
effects on the pharmacokinetics of prednisone/prednisolone.
Digoxin: Etoricoxib 120 mg administered once daily for 10 days to healthy volunteers did not alter
the steady-state plasma AUC0-24hr or renal elimination of digoxin. There was an increase in digoxin 
Cmax (approximately 33%). This increase is not generally important for most patients. However, 
patients at high risk of digoxin toxicity should be monitored for this when etoricoxib and digoxin 
are administered concomitantly.
Effect of etoricoxib on drugs metabolised by sulfotransferases
Etoricoxib is an inhibitor of human sulfotransferase activity, particularly SULT1E1, and has been 
shown to increase the serum concentrations of ethinyl estradiol. While knowledge about effects of 
multiple sulfotransferases is presently limited and the clinical consequences for many drugs are 
still being examined, it may be prudent to exercise care when administering etoricoxib concurrently 
with other drugs primarily metabolised by human sulfotransferases (e.g., oral salbutamol and 
minoxidil).
Effect of etoricoxib on drugs metabolised by CYP isoenzymes
Based on in vitro studies, etoricoxib is not expected to inhibit cytochromes P450 (CYP) 1A2, 2C9, 
2C19, 2D6, 2E1 or 3A4. In a study in healthy subjects, daily administration of etoricoxib 120 mg 
did not alter hepatic CYP3A4 activity as assessed by the erythromycin breath test.
Effects of other drugs on the pharmacokinetics of etoricoxib
The main pathway of etoricoxib metabolism is dependent on CYP enzymes. CYP3A4 appears to contribute 
to the metabolism of etoricoxib in vivo. In vitro studies indicate that CYP2D6, CYP2C9, CYP1A2 and 
CYP2C19 also can catalyse the main metabolic pathway, but their quantitative roles have not been 
studied in vivo.
Ketoconazole: Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400 mg once a day for 11
days to healthy volunteers, did not have any clinically important effect on the single-dose 
pharmacokinetics of 60 mg etoricoxib (43% increase in AUC).
Voriconazole and Miconazole: Co-administration of either oral voriconazole or topical miconazole
oral gel, strong CYP3A4 inhibitors, with etoricoxib caused a slight increase in exposure to 
etoricoxib, but is not considered to be clinically meaningful based on published data. Rifampicin: 
Co-administration of etoricoxib with rifampicin, a potent inducer of CYP enzymes, produced a 65% 
decrease in etoricoxib plasma concentrations. This interaction may result in
recurrence of symptoms when etoricoxib is co-administered with rifampicin. While this information 
may suggest an increase in dose, doses of etoricoxib greater than those listed for each indication 
have not been studied in combination with rifampicin and are therefore not recommended (see section 
4.2).
Antacids: Antacids do not affect the pharmacokinetics of etoricoxib to a clinically relevant 
extent.
 

Pregnancy
No clinical data on exposed pregnancies are available for etoricoxib. Studies in animals have shown 
reproductive toxicity (see section 5.3). The potential for human risk in pregnancy is
unknown. Etoricoxib, as with other medicinal products inhibiting prostaglandin synthesis, may
cause uterine inertia and premature closure of the ductus arteriosus during the last trimester. 
Etoricoxib is contraindicated in pregnancy (see section 4.3). If a woman becomes pregnant during 
treatment, etoricoxib must be discontinued.
Breastfeeding
It is not known whether etoricoxib is excreted in human milk. Etoricoxib is excreted in the milk of 
lactating rats. Women who use etoricoxib must not breast feed (see sections 4.3 and 5.3). Fertility
The use of etoricoxib, as with any drug substance known to inhibit COX-2, is not recommended in
women attempting to conceive.
 

Patients who experience dizziness, vertigo or somnolence while taking etoricoxib should refrain
from driving or operating machinery.
 

Summary of the safety profile
In clinical trials, etoricoxib was evaluated for safety in 9,295 individuals, including 6,757 
patients with OA, RA, chronic low back pain or ankylosing spondylitis (approximately 600 patients 
with OA or RA were treated for one year or longer).
In clinical studies, the undesirable effects profile was similar in patients with OA or RA treated
with etoricoxib for one year or longer.
In a clinical study for acute gouty arthritis, patients were treated with etoricoxib 120 mg once 
daily for eight days. The adverse experience profile in this study was generally similar to that 
reported in the combined OA, RA, and chronic low back pain studies.
In a cardiovascular safety outcomes programme of pooled data from three active comparator 
controlled trials, 17, 412 patients with OA or RA were treated with etoricoxib (60 mg or 90 mg) for 
a mean duration of approximately 18 months. The safety data and details from this programme are 
presented in section 5.1.
In clinical studies for acute postoperative dental pain following surgery including 614 patients 
treated with etoricoxib (90 mg or 120 mg), the adverse experience profile in these studies was 
generally similar to that reported in the combined OA, RA, and chronic low back pain studies. 
Tabulated list of adverse reactions
The following undesirable effects were reported at an incidence greater than placebo in clinical 
trials in patients with OA, RA, chronic low back pain or ankylosing spondylitis treated with 
etoricoxib 30 mg, 60 mg or 90 mg up to the recommended dose for up to 12 weeks; in the MEDAL 
Programme studies for up to 3½ years; in short term acute pain studies for up to 7 days;
or in post-marketing experience (see Table 1):
Table 1:

System Organ Class	Adverse Reactions	Frequency Category*
Infections and infestations	alveolar osteitis	Common
	gastroenteritis, upper respiratory infection, urinary tract infection	Uncommon
Blood and lymphatic system disorders	anaemia (primarily associated with gastrointestinal bleeding), leukopenia, thrombocytopenia	Uncommon
Immune system disorders	hypersensitivity‡ ß	Uncommon
	angioedema/anaphylactic /anaphylactoid reactions including shock‡	Rare
Metabolism and nutrition disorders	oedema/fluid retention	Common
	appetite increase or decrease, weight gain	Uncommon
Psychiatric disorders	anxiety, depression, mental acuity decreased, hallucinations‡	Uncommon
	confusion‡, restlessness‡	Rare
Nervous system disorders	dizziness, headache	Common
	dysgeusia, insomnia, paresthaesia/hypaesthesia, somnolence	Uncommon
Eye disorders	blurred vision, conjunctivitis	Uncommon
Ear and labyrinth disorders	tinnitus, vertigo	Uncommon
Cardiac disorders	palpitations, arrhythmia‡	Common
	atrial fibrillation, tachycardia‡, congestive heart failure, non-specific ECG changes, angina pectoris‡, myocardial infarction§	Uncommon
Vascular disorders	hypertension	Common
	flushing, cerebrovascular accident§, transient ischaemic attack, hypertensive crisis‡,vasculitis‡	Uncommon
Respiratory, thoracic and mediastinal disorders	bronchospasm‡	Common
	cough, dyspnoea, epistaxis	Uncommon
Gastrointestinal disorders	abdominal pain	Very common
	Constipation, flatulence, gastritis, heartburn/acid reflux, diarrhea, dyspepsia/epigastric discomfort, nausea, vomiting, oesophagitis, oral ulcer	Common
Hepatobiliary disorders	ALT increased, AST increased	Common
	hepatitis‡	Rare
	hepatic failure‡, jaundice‡	Rare‡
Skin and subcutaneous tissue disorders	ecchymosis	Common
	facial oedema, pruritus, rash, erythema‡, urticaria‡	Uncommon
	Stevens-Johnson syndrome‡, toxic epidermal necrolysis‡, fixed drug eruption‡	Rare‡
Musculoskeletal and connective tissue disorders	muscular cramp/spasm, musculoskeletal pain/stiffness	Uncommon
Renal and urinary disorders	proteinuria, serum creatinine increased, renal failure/renal insufficiency‡(see section 4.4)	Uncommon
General disorders and administration site conditions	asthenia/fatigue, flu-like disease	Common
	chest pain	Uncommon
Investigations	blood urea nitrogen increased, creatine phosphokinase increased, hyperkalaemia, uric acid increased	Uncommon
	blood sodium decreased	Rare

*Frequency Category: Defined for each Adverse Experience Term by the incidence reported in the 
clinical trials data
base: Very Common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100), Rare (≥1/10,000 
to
<1/1000), Very Rare (<1/10,000).
‡ This adverse reaction was identified through post-marketing surveillance. Its reported frequency 
has been estimated based upon the highest frequency observed across clinical trial data pooled by indication 
and approved
dose.
†The frequency category of “Rare” was defined per the Summary of Product Characteristics (SmPC) 
guidance (rev. 2, Sept 2009) on the basis of an estimated upper bound of the 95% confidence 
interval for 0 events given the number of subjects treated with CORREX in the analysis of the Phase 
III data pooled by dose and indication (n=15,470).
ß Hypersensitivity includes the terms "allergy", "drug allergy", "drug hypersensitivity", 
"hypersensitivity",
"hypersensitivity NOS", "hypersensitivity reaction" and "nonspecific allergy".
§Based on analyses of long-term placebo and active controlled clinical trials, selective COX-2 
inhibitors have been associated with an increased risk of serious thrombotic arterial events, 
including myocardial infarction and stroke.
The absolute risk increase for such events is unlikely to exceed 1% per year based on existing data 
(uncommon).
The following serious undesirable effects have been reported in association with the use of
NSAIDs and cannot be ruled out for etoricoxib: nephrotoxicity including interstitial nephritis and 
nephrotic syndrome.
Reporting of suspected adverse reactions
To report any side effects(s): Saudi Arabia:
National Pharmacovigilance and Drug Safety Center (NPC) Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
Toll free phone: 8002490000 Email: npc.drug@sfda.gov.sa Website: www.sfda.gov.sa/npc
Other GCC States: Please contact the relevant competent authority.
 

In clinical studies, administration of single doses of etoricoxib up to 500 mg and multiple doses 
up
to 150 mg/day for 21 days did not result in significant toxicity. There have been reports of acute 
overdosage with etoricoxib, although adverse experiences were not reported in the majority of 
cases. The most frequently observed adverse experiences were consistent with the safety profile for 
etoricoxib (e.g. gastrointestinal events, cardiorenal events).
In the event of overdose, it is reasonable to employ the usual supportive measures, e.g., remove 
unabsorbed material from the GI tract, employ clinical monitoring, and institute supportive 
therapy, if required.
Etoricoxib is not dialysable by haemodialysis; it is not known whether etoricoxib is dialysable by
peritoneal dialysis.
 

Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, non-steroids,
coxibs, ATC code: M01 AH05
Mechanism of Action
Etoricoxib is an oral, selective cyclo-oxygenase-2 (COX-2) inhibitor within the clinical dose 
range. Across clinical pharmacology studies, CORREX produced dose-dependent inhibition of COX-2 
without inhibition of COX-1 at doses up to 150 mg daily. Etoricoxib did not inhibit gastric 
prostaglandin synthesis and had no effect on platelet function.
Cyclooxygenase is responsible for generation of prostaglandins. Two isoforms, COX-1 and COX- 2, 
have been identified. COX-2 is the isoform of the enzyme that has been shown to be induced by 
pro-inflammatory stimuli and has been postulated to be primarily responsible for the synthesis of 
prostanoid mediators of pain, inflammation, and fever. COX-2 is also involved in ovulation, 
implantation and closure of the ductus arteriosus, regulation of renal function, and central 
nervous system functions (fever induction, pain perception and cognitive function). It may also 
play a role

in ulcer healing. COX-2 has been identified in tissue around gastric ulcers in man but its
relevance to ulcer healing has not been established. Clinical efficacy and safety
Efficacy
In patients with osteoarthritis (OA), etoricoxib 60 mg once daily provided significant improvements 
in pain and patient assessments of disease status. These beneficial effects were observed as early 
as the second day of therapy and maintained for up to 52 weeks. Studies with etoricoxib 30 mg once 
daily demonstrated efficacy superior to placebo over a 12 week treatment period (using similar 
assessments as the above studies). In a dose ranging study, etoricoxib 60 mg demonstrated 
significantly greater improvement than 30 mg for all 3 primary endpoints over 6 weeks of treatment. 
The 30 mg dose has not been studied in osteoarthritis of hands.
In patients with rheumatoid arthritis (RA), etoricoxib 60 mg and 90 mg once daily both provided 
significant improvements in pain, inflammation, and mobility. In studies evaluating the 60 mg and 
90 mg dose, these beneficial effects were maintained over the 12-week treatment periods. In a study 
evaluating the 60 mg dose compared to the 90 mg dose, etoricoxib 60 mg once daily and 90 mg once 
daily were both more effective than placebo. The 90 mg dose was superior to the 60 mg dose for 
Patient Global Assessment of Pain (0-100mm visual analogue scale), with an average improvement of 
-2.71 mm (95% CI: -4.98 mm, -0.45 mm).
In patients experiencing attacks of acute gouty arthritis, etoricoxib 120 mg once daily over an 
eight-day treatment period, relieved moderate to extreme joint pain and inflammation comparable to 
indomethacin 50 mg three times daily. Pain relief was observed as early as four hours after 
initiation of treatment.
In patients with ankylosing spondylitis, etoricoxib 90 mg once daily provided significant 
improvements in spine pain, inflammation, stiffness and function. The clinical benefit of 
etoricoxib was observed as early as the second day of therapy after initiation of treatment and was 
maintained throughout the 52-week treatment period. In a second study evaluating the 60 mg dose 
compared to the 90 mg dose, etoricoxib 60 mg daily and 90 mg daily demonstrated similar efficacy 
compared to naproxen 1,000 mg daily. Among inadequate responders to 60 mg daily for 6 weeks, dose 
escalation to 90 mg daily improved spinal pain intensity score (0-100 mm visual analogue scale) 
compared to continuing on 60 mg daily, with an average improvement of -2.70 mm (95% CI: -4.88 mm, 
-0.52 mm).
In a clinical study evaluating postoperative dental pain, etoricoxib 90 mg was administered once 
daily for up to three days. In the subgroup of patients with moderate pain at baseline, etoricoxib 
90 mg demonstrated a similar analgesic effect to that of ibuprofen 600 mg (16.11 vs. 16.39; 
P=0.722), and greater than that of paracetamol/codeine 600 mg/60 mg (11.00; P<0.001) and placebo 
(6.84; P<0.001) as measured by total pain relief over the first 6 hours (TOPAR6). The
proportion of patients reporting rescue medication usage within the first 24 hours of dosing was
40.8% for etoricoxib 90 mg, 25.5% for ibuprofen 600 mg Q6h, and 46.7% for paracetamol/codeine 600 
mg/60 mg Q6h compared to 76.2% for placebo. In this study, the median onset of action (perceptible 
pain relief) of 90 mg etoricoxib was 28 minutes after dosing.
Safety
Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) Programme
The MEDAL Programme was a prospectively designed Cardiovascular (CV) Safety Outcomes Programme of 
pooled data from three randomized, double-blind active comparator controlled trials, the MEDAL 
study, EDGE II and EDGE.
The MEDAL Study, was an endpoint driven CV Outcomes study in 17,804 OA and 5,700 RA patients 
treated with etoricoxib 60 (OA) or 90 mg (OA and RA) or diclofenac 150 mg daily for a mean period 
of 20.3 months (maximum of 42.3 months, median 21.3 months). In this trial, only
serious adverse events and discontinuations due to any adverse events were recorded.
The EDGE and EDGE II studies compared the gastrointestinal tolerability of etoricoxib versus 
diclofenac. The EDGE study included 7,111 OA patients treated with a dose of etoricoxib 90 mg daily 
(1.5 times the dose recommended for OA) or diclofenac 150 mg daily for a mean period of

9.1 months (maximum 16.6 months, median 11.4 months). The EDGE II study included 4,086 RA
patients treated with etoricoxib 90 mg daily or diclofenac 150 mg daily for a mean period of 19.2 
months (maximum 33.1 months, median 24 months).
In the pooled MEDAL Programme, 34,701 patients with OA or RA were treated for a mean duration of 
17.9 months (maximum 42.3 months, median 16.3 months) with approximately 12,800 patients receiving 
treatment for more than 24 months. Patients enrolled in the Programme had a wide range of 
cardiovascular and gastrointestinal risk factors at baseline. Patients with a recent history of 
myocardial infarction, coronary artery bypass grafting or percutaneous coronary
intervention within 6 months preceding enrollment were excluded. Use of gastroprotective agents
and low dose aspirin were permitted in the studies. Overall Safety:
There was no significant difference between etoricoxib and diclofenac in the rate of cardiovascular 
thrombotic events. Cardiorenal adverse events were observed more frequently with etoricoxib than 
with diclofenac, and this effect was dose-dependent (see specific results below). Gastrointestinal 
and hepatic adverse events were observed significantly more frequently with diclofenac than 
etoricoxib. The incidence of adverse experiences in EDGE and EDGE II and of adverse experiences 
considered serious or resulting in discontinuation in the MEDAL study was higher with etoricoxib 
than diclofenac.
Cardiovascular safety results:
The rate of confirmed thrombotic cardiovascular serious adverse events (consisting of cardiac, 
cerebrovascular, and peripheral vascular events) was comparable between etoricoxib and diclofenac, 
and data are summarized in the table below. There were no statistically significant differences in 
thrombotic event rates between etoricoxib and diclofenac across all subgroups
analyzed including patient categories across a range of baseline cardiovascular risk. When 
considered separately, the relative risks for confirmed thrombotic cardiovascular serious adverse
 events with etoricoxib 60 mg or 90 mg compared with diclofenac 150 mg were similar.
 

Table 2: Rates of Confirmed Thrombotic CV Events (Pooled MEDAL Programme)
	Etoricoxib (N=16,819) 25,836 Patient-Years	Diclofenac (N=16,483) 24,766 Patient-Years	Between Treatment Comparison
	Rate† (95% CI)	Rate† (95% CI)	Relative Risk (95% CI)
Confirmed Thrombotic Cardiovascular Serious Adverse Events
Per-protocol	1.24 (1.11, 1.38)	1.30 (1.17, 1.45)	0.95 (0.81, 1.11)
Intent-to-treat	1.25 (1.14, 1.36)	1.19 (1.08, 1.30)	1.05 (0.93, 1.19)
Confirmed Cardiac Events
Per-protocol	0.71 (0.61, 0.82)	0.78 (0.68, 0.90)	0.90 (0.74, 1.10)
Intent-to-treat	0.69 (0.61, 0.78)	0.70 (0.62, 0.79)	0.99 (0.84, 1.17)
Confirmed Cerebrovascular Events
Per-protocol	0.34 (0.28, 0.42)	0.32 (0.25, 0.40)	1.08 (0.80, 1.46)
Intent-to-treat	0.33 (0.28, 0.39)	0.29 (0.24, 0.35)	1.12 (0.87, 1.44)
Confirmed Peripheral Vascular Events
Per-protocol	0.20 (0.15, 0.27)	0.22 (0.17, 0.29)	0.92 (0.63, 1.35)
Intent-to-treat	0.24 (0.20, 0.30)	0.23 (0.18, 0.28)	1.08 (0.81, 1.44)

^† Events per 100 Patient-Years; CI=confidence interval
N=total number of patients included in Per-protocol population
Per-protocol: all events on study therapy or within 14 days of discontinuation (excluded: patients 
who took < 75% of
their study medication or took non-study NSAIDs >10% of the time).

Intent-to-treat: all confirmed events up to the end of the trial (included patients potentially exposed to non-study interventions following discontinuation of study medication). Total number of patients randomised, n= 17,412 on etoricoxib and 17,289 on diclofenac.

CV mortality, as well as overall mortality, was similar between the etoricoxib and diclofenac
treatment groups. Cardiorenal Events:
Approximately 50% of patients enrolled in the MEDAL study had a history of hypertension at 
baseline. In the study, the incidence of discontinuations due to hypertension-related adverse 
events was statistically significantly higher for etoricoxib than for diclofenac. The incidence of
congestive heart failure adverse events (discontinuations and serious events) occurred at similar 
rates on etoricoxib 60 mg compared to diclofenac 150 mg but was higher for etoricoxib 90 mg
compared to diclofenac 150 mg (statistically significant for 90 mg etoricoxib vs. 150 mg diclofenac
in MEDAL OA cohort). The incidence of confirmed congestive heart failure adverse events (events 
that were serious and resulted in hospitalisation or a visit to an emergency department) was 
non-significantly higher with etoricoxib than diclofenac 150 mg, and this effect was dose- 
dependent. The incidence of discontinuations due to oedema-related adverse events was higher for 
etoricoxib than diclofenac 150 mg, and this effect was dose-dependent (statistically significant 
for etoricoxib 90 mg, but not for etoricoxib 60 mg).
The cardiorenal results for EDGE and EDGE II were consistent with those described for the
MEDAL Study.

In the individual MEDAL Programme studies, for etoricoxib (60 mg or 90 mg), the absolute
incidence of discontinuation in any treatment group was up to 2.6% for hypertension, up to 1.9% for 
oedema, and up to 1.1% for congestive heart failure, with higher rates of discontinuation
observed with etoricoxib 90 mg than etoricoxib 60 mg. MEDAL Programme Gastrointestinal Tolerability 
Results:
A significantly lower rate of discontinuations of treatment for any clinical (e.g., dyspepsia, 
abdominal pain, ulcer) GI adverse event was observed with etoricoxib compared with diclofenac 
within each of the three component studies of the MEDAL Programme. The rates of
discontinuations due to adverse clinical GI events per hundred patient-years over the entire
period of study were as follows: 3.23 for etoricoxib and 4.96 for diclofenac in the MEDAL Study;
9.12 with etoricoxib and 12.28 with diclofenac in the EDGE study; and 3.71 with etoricoxib and
4.81 with diclofenac in the EDGE II study.
MEDAL Programme Gastrointestinal Safety Results:
Overall upper GI events were defined as perforations, ulcers and bleeds. The subset of overall 
upper GI events considered complicated included perforations, obstructions, and complicated 
bleeding; the subset of upper GI events considered uncomplicated included uncomplicated bleeds and 
uncomplicated ulcers. A significantly lower rate of overall upper GI events was observed with 
etoricoxib compared to diclofenac. There was no significant difference between etoricoxib and 
diclofenac in the rate of complicated events. For the subset of upper GI haemorrhage events 
(complicated and uncomplicated combined), there was no significant difference between etoricoxib 
and diclofenac. The upper GI benefit for etoricoxib compared with diclofenac was not statistically 
significant in patients taking concomitant low-dose aspirin (approximately 33% of patients).
The rates per hundred patient-years of confirmed complicated and uncomplicated upper GI clinical 
events (perforations, ulcers and bleeds (PUBs)) were 0.67 (95% CI 0.57, 0.77) with etoricoxib and 
0.97 (95% CI 0.85, 1.10) with diclofenac, yielding a relative risk of 0.69 (95% CI
0.57, 0.83).
The rate for confirmed upper GI events in elderly patients was evaluated and the largest reduction 
was observed in patients ≥ 75 years of age (1.35 [95% CI 0.94, 1.87] vs. 2.78 [95% CI
2.14, 3.56] events per hundred patient-years for etoricoxib and diclofenac, respectively.

The rates of confirmed lower GI clinical events (small or large bowel perforation, obstruction, or
haemorrhage, (POBs)) were not significantly different between etoricoxib and diclofenac. MEDAL 
Programme Hepatic Safety Results:
Etoricoxib was associated with a statistically significantly lower rate of discontinuations due to 
hepatic-related adverse experiences than diclofenac. In the pooled MEDAL Programme, 0.3% of 
patients on etoricoxib and 2.7% of patients on diclofenac discontinued due to hepatic-related 
adverse experiences. The rate per hundred patient-years was 0.22 on etoricoxib and 1.84 for 
diclofenac (p-value was <0.001 for etoricoxib vs. diclofenac). However, most hepatic adverse
experiences in the MEDAL Programme were non-serious.
Additional Thrombotic Cardiovascular Safety Data
In clinical studies excluding the MEDAL Programme Studies, approximately 3,100 patients were 
treated with etoricoxib ≥60 mg daily for 12 weeks or longer. There was no discernible difference in 
the rate of confirmed serious thrombotic cardiovascular events between patients receiving 
etoricoxib ≥60 mg, placebo, or non-naproxen NSAIDs. However, the rate of these events was higher in 
patients receiving etoricoxib compared with those receiving naproxen 500 mg twice daily. The 
difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and selective COX-2 
inhibitors may be of clinical significance in patients at risk of thrombo-embolic events. Selective 
COX-2 inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin 
without affecting platelet thromboxane. The clinical relevance of these observations has not been 
established.
Additional Gastrointestinal Safety Data
In two 12-week double-blind endoscopy studies, the cumulative incidence of gastroduodenal 
ulceration was significantly lower in patients treated with etoricoxib 120 mg once daily than in 
patients treated with either naproxen 500 mg twice daily or ibuprofen 800 mg three times daily. 
Etoricoxib had a higher incidence of ulceration as compared to placebo.
Renal Function Study in the Elderly
A randomized, double-blind, placebo-controlled, parallel-group study evaluated the effects of 15 
days of treatment of etoricoxib (90 mg), celecoxib (200 mg bid), naproxen (500 mg bid) and placebo 
on urinary sodium excretion, blood pressure, and other renal function parameters in subjects 60 to 
85 years of age on a 200-mEq/day sodium diet. Etoricoxib, celecoxib, and naproxen had similar 
effects on urinary sodium excretion over the 2 weeks of treatment. All active comparators showed an 
increase relative to placebo with respect to systolic blood pressures; however, etoricoxib was 
associated with a statistically significant increase at Day 14 when compared to celecoxib and 
naproxen (mean change from baseline for systolic blood pressure:
etoricoxib 7.7 mmHg, celecoxib 2.4 mmHg, naproxen 3.6 mmHg).
 

 

 

Absorption
Orally administered etoricoxib is well absorbed. The absolute bioavailability is approximately 
100%. Following 120 mg once-daily dosing to steady state, the peak plasma concentration (geometric 
mean Cmax = 3.6 µg/ml) was observed at approximately 1 hour (Tmax) after administration to fasted 
adults. The geometric mean area under the curve (AUC0-24hr) was 37.8
µg•hr/ml. The pharmacokinetics of etoricoxib are linear across the clinical dose range.
Dosing with food (a high-fat meal) had no effect on the extent of absorption of etoricoxib after 
administration of a 120-mg dose. The rate of absorption was affected, resulting in a 36% decrease 
in Cmax and an increase in Tmax by 2 hours. These data are not considered clinically significant. 
In clinical trials, etoricoxib was administered without regard to food intake. Distribution
Etoricoxib is approximately 92% bound to human plasma protein over the range of concentrations of 
0.05 to 5 µg/ml. The volume of distribution at steady state (Vdss) was approximately 1,20l in 
humans.
Etoricoxib crosses the placenta in rats and rabbits, and the blood-brain barrier in rats.
Biotransformation

Etoricoxib is extensively metabolised with <1% of a dose recovered in urine as the parent drug.
The major route of metabolism to form the 6'-hydroxymethyl derivative is catalyzed by CYP enzymes. 
CYP3A4 appears to contribute to the metabolism of etoricoxib in vivo. In vitro studies indicate 
that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can catalyse the main metabolic pathway, but their 
quantitative roles in vivo have not been studied.
Five metabolites have been identified in man. The principal metabolite is the 6'-carboxylic acid 
derivative of etoricoxib formed by further oxidation of the 6'-hydroxymethyl derivative. These 
principal metabolites either demonstrate no measurable activity or are only weakly active as COX-2 
inhibitors. None of these metabolites inhibit COX-1.
Elimination
Following administration of a single 25-mg radiolabeled intravenous dose of etoricoxib to healthy 
subjects, 70% of radioactivity was recovered in urine and 20% in faeces, mostly as metabolites. 
Less than 2% was recovered as unchanged drug.
Elimination of etoricoxib occurs almost exclusively through metabolism followed by renal excretion. 
Steady state concentrations of etoricoxib are reached within seven days of once daily 
administration of 120 mg, with an accumulation ratio of approximately 2, corresponding to a half- 
life of approximately 22 hours. The plasma clearance after a 25-mg intravenous dose is estimated to 
be approximately 50 ml/min.
Characteristics in patients
Elderly patients: Pharmacokinetics in the elderly (65 years of age and older) are similar to those
in the young.
Gender: The pharmacokinetics of etoricoxib are similar between men and women.
Hepatic impairment: Patients with mild hepatic dysfunction (Child-Pugh score 5-6) administered 
etoricoxib 60 mg once daily had an approximately 16% higher mean AUC as compared to healthy 
subjects given the same regimen. Patients with moderate hepatic dysfunction (Child-Pugh score 7-9) 
administered etoricoxib 60 mg every other day had similar mean AUC to the healthy subjects given 
etoricoxib 60 mg once daily; etoricoxib 30 mg once daily has not been studied in this population. 
There are no clinical or pharmacokinetic data in patients with severe hepatic dysfunction 
(Child-Pugh score ≥10). (See sections 4.2 and 4.3.)
Renal impairment: The pharmacokinetics of a single dose of etoricoxib 120 mg in patients with
moderate to severe renal insufficiency and patients with end-stage renal disease on haemodialysis 
were not significantly different from those in healthy subjects. Haemodialysis contributed 
negligibly to elimination (dialysis clearance approximately 50 ml/min). (See sections 4.3 and 4.4.)
Paediatric patients: The pharmacokinetics of etoricoxib in paediatric patients (<12 years old) have
not been studied.
In a pharmacokinetic study (n=16) conducted in adolescents (aged 12 to 17) the pharmacokinetics in 
adolescents weighing 40 to 60 kg given etoricoxib 60 mg once daily and adolescents >60 kg given 
etoricoxib 90 mg once daily were similar to the pharmacokinetics in adults given etoricoxib 90 mg 
once daily. Safety and effectiveness of etoricoxib in paediatric
patients have not been established (see section 4.2).
 

In preclinical studies, etoricoxib has been demonstrated not to be genotoxic. Etoricoxib was not
carcinogenic in mice. Rats developed hepatocellular and thyroid follicular cell adenomas at >2- 
times the daily human dose [90 mg] based on systemic exposure when dosed daily for approximately 
two years. Hepatocellular and thyroid follicular cell adenomas observed in rats are considered to 
be a consequence of rat-specific mechanism related to hepatic CYP enzyme induction. Etoricoxib has 
not been shown to cause hepatic CYP3A enzyme induction in humans. In the rat, gastrointestinal 
toxicity of etoricoxib increased with dose and exposure time. In the 14- week toxicity study 
etoricoxib caused gastrointestinal ulcers at exposures greater than those seen
in man at the therapeutic dose. In the 53- and 106-week toxicity study, gastrointestinal ulcers
were also seen at exposures comparable to those seen in man at the therapeutic dose. In dogs,
renal and gastrointestinal abnormalities were seen at high exposures.
Etoricoxib was not teratogenic in reproductive toxicity studies conducted in rats at 15 mg/kg/day 
(this represents approximately 1.5 times the daily human dose [90 mg] based on systemic exposure). 
In rabbits, a treatment related increase in cardiovascular malformations was observed at exposure 
levels below the clinical exposure at the daily human dose (90 mg). However no treatment-related 
external or skeletal foetal malformations were observed. In rats and rabbits, there was a dose 
dependent increase in post implantation loss at exposures greater than or equal
to 1.5 times the human exposure (see sections 4.3 and 4.6).
Etoricoxib is excreted in the milk of lactating rats at concentrations approximately two-fold those 
in plasma. There was a decrease in pup body weight following exposure of pups to milk from
dams administered etoricoxib during lactation.
 

Microcrystalline cellulose
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Di-Bastic calcium Phosphate anhydrous Magnesium stearate
Opadry II white Yellow Iron Oxide
FD& C Blue #1 Lake
 

Not applicable.

2 years.

Store below 30 C.

90mg
Aluminium/aluminium blisters in packs containing 14 tablets
120 mg
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Not all pack sizes may be marketed.
 

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Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.