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FINAL TEXT:
24-July-2012
ARCOXIA® W (etoricoxib)
PRESCRIBING INFORMATION
Refer to Summary of Product Characteristics before prescribing
Adverse events should be reported. Reporting forms and information can be
found at reported to MSD (tel: 01992 467272).

PRESENTATION
Tablets: 30 mg, 60 mg, 90 mg and 120 mg tablets each containing 30 mg, 60 mg, 90 mg or
120 mg of etoricoxib respectively.
USES
Symptomatic relief of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis
(AS), the short term treatment of moderate pain associated with dental surgery and the pain
and signs of inflammation associated with acute gouty arthritis. Base the decision to
prescribe a selective COX-2 inhibitor on an assessment of the individual patient’s overall
risks.
DOSAGE AND ADMINISTRATION
Take orally with or without food. Onset of action may be faster when taken without food, and
should be considered when rapid relief is needed. Use the lowest effective daily dose for the
shortest duration possible, as cardiovascular risks may increase with dose and duration of
exposure. Re-evaluate periodically patient's need, especially in osteoarthritis patients.
Osteoarthritis: 30 mg once daily, increasing to 60 mg in patients with insufficient relief from
symptoms. Rheumatoid arthritis and ankylosing spondylitis: 90 mg once daily. Acute gouty
arthritis: 120 mg once daily for the acute symptomatic period only and limited to a
maximum of 8 days. Postoperative dental surgery pain: 90 mg once daily, limited to a
maximum of 3 days. Some patients may require additional postoperative analgesia. Doses
greater than these have either not been studied or have not demonstrated additional efficacy.
Hepatic insufficiency: mild (Child-Pugh score 5-6): do not exceed a dose of 60 mg daily;
moderate (Child-Pugh score 7-9): do not exceed 30 mg once daily; severe: contra-
indicated, see below. Renal insufficiency: creatinine clearance < 30 ml/min: contra-
indicated; ≥ 30 ml/min: no dosage adjustment necessary. Elderly: exercise caution.

CONTRA-INDICATIONS
Hypersensitivity to any component of this product. Active peptic ulceration or gastro-
intestinal (GI) bleeding. Patients who have experienced bronchospasm, acute rhinitis, nasal
polyps, angioneurotic oedema or urticaria or allergic type reactions after aspirin or NSAIDs
including COX-2 inhibitors. Pregnancy and lactation. Severe hepatic dysfunction (serum
albumin <25 g/l or Child-Pugh score ≥10). Estimated 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.
PRECAUTIONS
Gastro-intestinal effects: Upper GI complications (perforations, ulcers or bleedings), some
with fatal outcome have occurred in patients taking etoricoxib. Caution is advised in patients
most at risk of developing a GI complication with NSAIDs: elderly, those on any other
NSAID or aspirin concomitantly, or those with a prior history of GI disease. There is a
further increase in the risk of GI adverse effects (GI ulceration or other GI complications)
when etoricoxib is taken together with aspirin (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.
Cardiovascular: Trials suggest that the selective COX-2 inhibitor class of drugs may be
associated with a risk of thrombotic events (especially MI and stroke), relative to placebo and
some NSAIDs. As the cardiovascular risks of etoricoxib may increase with dose and duration
of exposure, use for the shortest duration possible and at the lowest effective dose. Re-
evaluate periodically the patient’s need for symptomatic relief and response to therapy,
especially in those with osteoarthritis. Patients with significant risk factors for cardiovascular
events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated
with etoricoxib after careful consideration. COX-2 selective inhibitors are not a substitute for
acetylsalicylic acid for prophylaxis of cardiovascular thromboembolic diseases because of
their lack of antiplatelet effect, therefore do not discontinue antiplatelet therapies.
Renal effects: Consider monitoring renal function in patients with pre-existing significantly
impaired renal function, uncompensated heart failure, or cirrhosis.

Fluid retention, oedema and hypertension: Exercise caution in patients with a history of
cardiac failure, left ventricular dysfunction, or hypertension and in those with pre-existing
oedema from any other reason, as fluid retention, oedema and hypertension have been
observed in patients taking etoricoxib. Take appropriate measures, including discontinuation
of etoricoxib where there is clinical evidence of deterioration in the condition of these
patients. Etoricoxib may be associated with more frequent and severe hypertension than
some other NSAIDs and selective COX-2 inhibitors, particularly at high doses. Control
hypertension before treatment and pay special attention to blood pressure monitoring during
treatment with etoricoxib. Monitor blood pressure within two weeks after starting treatment
and periodically thereafter. If blood pressure rises significantly, consider alternative
treatment.
Hepatic effects: Elevations of ALT and/or AST (≥3 times the upper limit of normal) have
been reported in approximately 1% of patients treated in trials with etoricoxib 30, 60 and 90
mg for up to one year. Monitor any patient with symptoms /signs of liver dysfunction or in
whom an abnormal liver function test has occurred. Discontinue etoricoxib if signs of hepatic
insufficiency occur, or if persistently abnormal liver function tests (3 times the upper limit of
normal) are detected.
General
Maintain appropriate medical supervision when treating the elderly and patients with renal,
hepatic or cardiac dysfunction with etoricoxib. Use caution when initiating treatment in
patients with considerable dehydration. 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,
associated with the use of NSAIDs and some selective COX-2 inhibitors. Discontinue at the
first signs of skin rash, mucosal lesions or any other signs of hypersensitivity. Etoricoxib may mask fever. Use of etoricoxib is not recommended in women attempting to conceive. ‘Arcoxia’ tablets contain lactose: do not use in patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Interactions (pharmacodynamic): Oral anticoagulants: Exercise caution when coadministering with warfarin and other oral anticoagulants. Closely monitor the prothrombin time INR when therapy is initiated or the dose changed in patients receiving oral anticoagulants or similar agents, particularly in the first few days. Diuretics, ACE-inhibitors and Angiotensin II Antagonists: NSAIDS may reduce the effect of diuretics and antihypertensive drugs. In some patients with compromised renal function, the co-administration of an ACE inhibitor or AIIA and cyclo-oxygenase inhibitors may result in further deterioration of renal function including possible acute renal failure, which is usually reversible. Administer cautiously, especially in the elderly. Patients should be adequately hydrated. Consider monitoring renal function at initiation of therapy and periodically thereafter. Aspirin: etoricoxib can be used concomitantly with aspirin at doses used for cardiovascular prophylaxis (low-dose aspirin). However, concomitant administration of low-dose aspirin 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 aspirin above those for cardiovascular prophylaxis, or with other NSAIDS is not recommended. Ciclosporin/tacrolimus: monitor renal function when etoricoxib and either ciclosporin or tacrolimus is used in combination. Interactions (pharmacokinetic) The effect of etoricoxib on the pharmacokinetics of other drugs: Lithium: the plasma concentration of lithium is increased by NSAIDS, therefore monitor and adjust blood lithium and lithium dosage if necessary. Methotrexate: adequate monitoring is recommended for methotrexate-related toxicity when etoricoxib and methotrexate are administered concomitantly. Oral Contraceptives (OC): Administration of etoricoxib 60 mg with an OC containing 35 mcg ethinyl estradiol (EE) and 0.5 to 1 mg norethindrone for 21 days increased the steady state AUC0-24hr of EE by 37%. Administration of etoricoxib 120 mg with the same OC, concomitantly or separated by 12 hours, increased the steady state AUC0-24hr of EE by 50 to 60%. Consider this increase in EE concentration 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. Hormone Replacement Therapy: 120 mg etoricoxib administered with 0.625 mg Premarin™ (Wyeth) for 28 days increased the mean steady state AUC0-24hr of unconjugated estrone (41%), equilin (76%) and 17-β-estradiol (22%). Although the clinical significance is unknown, take into consideration the increase in estrogenic concentration when selecting HRT as the increase in estrogen exposure might increase the risk of adverse events associated with HRT. Digoxin: Patients at high risk of digoxin toxicity should be monitored for an increase in digoxin Cmax 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. 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. 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 voriconazole or topical miconazole oral gel with
etoricoxib caused a slight increase in exposure to etoricoxib, but it is thought not 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, an interaction which may result in recurrence of symptoms. Antacids:
Antacids do not affect the pharmacokinetics of etoricoxib to a clinically relevant extent.
Pregnancy: contra-indicated in the first, second and third trimesters of pregnancy.
Breastfeeding: contra-indicated.
SIDE EFFECTS
Refer to Summary of Product Characteristics for complete information on side-effects
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 AS, treated with etoricoxib
30 mg, 60 mg or 90 mg for up to 12 weeks, or in the MEDAL Programme studies, or in post-
marketing experience:
[Very common ( >1/10) Common ( >1/100, <1/10) Uncommon ( >1/1000, <1/100) Rare
( >1/10,000, <1/1000) Very rare ( <1/10,000) not known (cannot be estimated from the
available data)]
Infections and infestations: Uncommon: gastro-enteritis, upper respiratory infection,
urinary tract infection.
Blood and lymphatic system disorders: Uncommon: anaemia (primarily associated with
gastrointestinal bleeding), leukopenia, thrombocytopenia
Immune system disorders: Very rare: hypersensitivity reactions including angioedema,
anaphylactic/anaphylactoid reactions including shock.
Metabolism and nutrition disorders: Common: oedema/fluid retention. Uncommon:
appetite increase or decrease, weight gain.
Psychiatric disorders: Uncommon: anxiety, depression, mental acuity decreased. Very rare:
confusion, hallucinations. Not known: restlessness
Nervous system disorders: Common: dizziness, headache. Uncommon: dysgeusia,
insomnia, paraesthesia/hypaesthesia, somnolence.
Eye disorders: Uncommon: blurred vision, conjunctivitis.
Ear and labyrinth disorders: Uncommon: tinnitus, vertigo.
Cardiac disorders: Common: palpitations. Uncommon: atrial fibrillation, congestive heart
failure, non-specific ECG changes, angina pectoris, myocardial infarction*. Not known:
tachycardia, arrhythmia.
Vascular disorders: Common: hypertension. Uncommon: flushing, cerebrovascular
accident*, transient ischaemic attack. Very rare: hypertensive crisis. Not known: vasculitis
Respiratory, thoracic and mediastinal disorders: Uncommon: cough, dyspnoea, epistaxis.
Very rare: bronchospasm.
Gastro-intestinal disorders: Common: gastro-intestinal disorders (e.g. abdominal pain,
flatulence, heartburn), diarrhoea, dyspepsia, epigastric discomfort, nausea. Uncommon:
abdominal distension, acid reflux, bowel movement pattern change, constipation, dry mouth,
gastroduodenal ulcer, irritable bowel syndrome, oesophagitis, oral ulcer, vomiting, gastritis.
Very rare: peptic ulcers including gastro-intestinal perforation and bleeding (mainly in the
elderly). Not known: pancreatitis.
Hepatobiliary disorders: Common: ALT increased, AST increased. Very rare: hepatitis. Not
known: jaundice, hepatic failure
Skin and subcutaneous tissue disorders: Common: ecchymosis. Uncommon: facial
oedema, pruritus, rash. Rare: erythema. Very rare: urticaria, Stevens-Johnson syndrome,
toxic epidermal necrolysis. Not known: fixed drug eruption.
Musculoskeletal and connective tissue disorders: Common: alveolar osteitis. Uncommon:
muscular cramp/spasm, musculoskeletal pain/stiffness.
Renal and urinary disorders: Uncommon: proteinuria, serum creatinine increased. Very
rare: renal insufficiency, including renal failure.
General disorders and administration site conditions: Common: asthenia/fatigue, flu-like
disease. Uncommon: chest pain.
Investigations: Uncommon: blood urea nitrogen increased, creatine phosphokinase
increased, hyperkalaemia, uric acid increased. Rare: blood sodium decreased.

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; hepatotoxicity including hepatic failure.
* 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 for such events is unlikely to exceed 1% per year
based on existing data (uncommon).
PACKAGE QUANTITIES AND BASIC NHS COST
30 mg: packs of 28 tablets £13.99
60 mg: packs of 28 tablets £20.11
90 mg: packs of 28 tablets £22.96
120 mg Tablets: packs of 7 tablets £6.03 and packs of 28 tablets £24.11
Marketing Authorisation numbers
Tablet 30 mg

Marketing Authorisation holder
Merck Sharp & Dohme Limited
Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK
Date of review of prescribing information: July 2012 Merck Sharp & Dohme Limited 2012. All rights reserved. PI.ACX.12.UK.3679 (R02)

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