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SafetyScorer

Is Etoricoxib safe?

Etoricoxib

Etoricoxib (Arcoxia) is a COX-2 inhibitor sold in the UK and much of the world, but never approved in the US. In a 34,701-patient programme its heart risk matched high-dose diclofenac with fewer stomach problems, but it raises blood pressure more than most painkillers.

High confidence#53 of 99 medications
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Brand
Arcoxia (Organon in the UK)
Type
COX-2 selective NSAID (coxib); prescription only
UK doses
30 to 60 mg a day for osteoarthritis; 60 to 90 mg for rheumatoid arthritis and ankylosing spondylitis; 120 mg for acute gout, at most 8 days
Do not take if
Heart disease, past stroke, peripheral arterial disease, heart failure (NYHA II to IV), or blood pressure persistently above 140/90 mmHg
Status in the US
Not approved; FDA non-approvable letter on 27 April 2007
UK licence
Since 13 February 2002
Half-life
About 22 hours
Controlled substance
No

How the score breaks down

The overall score is the weighted average of these factors. Scoring rules

  • Serious side effects30% of score

    52 out of 100, Weak

    In MEDAL (34,701 patients) heart attacks and strokes ran at 1.24 per 100 patient-years, against 1.30 on diclofenac 150 mg, and stomach events were lower (0.67 vs 0.97). But more people stopped for high blood pressure, and heart failure rose at 90 mg.

  • Overdose margin20% of score

    85 out of 100, Excellent

    The UK label says single doses up to 500 mg, and 150 mg a day for 21 days, caused no significant toxicity in studies. Most reported overdoses had no side effects. It cannot be removed by haemodialysis.

  • Interactions15% of score

    55 out of 100, Fair

    At 60 mg it raised ethinylestradiol from the Pill by 37%, and 50% to 60% at 120 mg. It raised warfarin's INR about 13% and methotrexate levels 28% at 120 mg; rifampicin cut etoricoxib levels 65%. The usual NSAID bleeding, kidney and lithium effects apply.

  • Dependence and misuse15% of score

    97 out of 100, Excellent

    No addiction, withdrawal or misuse potential, and not a Controlled substanceA medicine or drug that the law restricts because it can be misused or cause dependence. Countries group them into schedules or classes.More in the glossary.

  • Regulatory warnings10% of score

    30 out of 100, Poor

    The FDA refused approval in April 2007 after its advisers voted 20 to 1 against. The EU ContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary coxibs in heart disease in 2005 and, after a 2008 review, in blood pressure persistently above 140/90 mmHg. Contraindicated in pregnancy and breastfeeding.

  • Track record10% of score

    85 out of 100, Excellent

    Licensed in the UK since February 2002 and sold in 63 countries by 2007. The MEDAL programme is one of the largest NSAID safety trials, but there is no US market data and fewer population studies than for the older NSAIDs.

Is etoricoxib safe?

For adults without heart disease and with well-controlled blood pressure, etoricoxib is an effective arthritis painkiller that is easier on the stomach than older NSAIDs. For anyone with heart disease, a past stroke or high blood pressure that is not under control, it is not an option: the UK label rules it out.

Etoricoxib, sold as Arcoxia, is a coxib like celecoxib, and a close chemical relative of rofecoxib (Vioxx), which was withdrawn in 2004. It has been licensed in the UK since 2002 and was sold in 63 countries by 2007, but never in the US. We score it 67, below celecoxib (74) and just below diclofenac (69), the drug it was tested against.

Why the FDA said no

Merck asked the FDA to approve a 60 mg dose for osteoarthritis in December 2003, then waited through the Vioxx withdrawal. In April 2007 the FDA's arthritis advisers voted 20 to 1 against, and on 27 April 2007 the agency sent a non-approvable letter asking for more data on benefits and risks. Reports at the time said the advisers judged that the heart risks outweighed the benefit for arthritis pain.

Europe took a different view. The European Medicines Agency kept coxibs on the market in 2005 but barred them for people with established heart disease, stroke or peripheral arterial disease. A 2008 EU review of the 90 mg dose added a firm rule on blood pressure, and in 2016 the recommended starting dose for rheumatoid arthritis and ankylosing spondylitis dropped from 90 mg to 60 mg.

What the MEDAL trials found

The MEDAL programme pooled three trials and 34,701 people with osteoarthritis or rheumatoid arthritis, who took etoricoxib 60 or 90 mg or diclofenac 150 mg a day for an average of 18 months.

Outcome (per 100 patient-years)EtoricoxibDiclofenac 150 mg
Heart attack, stroke and other clots1.241.30
Upper stomach and bowel events0.670.97
Complicated stomach events (bleeds, perforations)0.300.32

Etoricoxib was no worse than diclofenac for the heart, and it caused fewer ulcers. The catch is the comparison. Diclofenac at 150 mg is itself one of the higher-risk NSAIDs for the heart, which is why Europe restricted it in 2013. A 2011 review of population studies found etoricoxib raised heart attack and stroke risk about twofold (2.05 times), a significantly higher risk than ibuprofen or naproxen, though from only four small studies.

Blood pressure and heart failure

This is where etoricoxib differs most from other painkillers. The UK label warns it may cause more frequent and severe high blood pressure than some other NSAIDs and coxibs, especially at higher doses. In MEDAL, more patients stopped etoricoxib than diclofenac because of high blood pressure, up to 2.6% in a single trial, and heart failure was more common at 90 mg than on diclofenac.

The label asks for blood pressure to be under control before starting, checked within two weeks, and checked regularly after that. If it rises significantly, a different painkiller should be used. People with heart failure (NYHA class II to IV), severe kidney disease or inflammatory bowel disease must not take it.

Interactions to know about

Etoricoxib has a few interactions that the older NSAIDs do not share:

  • The Pill and HRT. It raises ethinylestradiol levels by 37% at 60 mg and by 50% to 60% at 120 mg, and also raises oestrogen from HRT.
  • Warfarin. At 120 mg it raised the INR by about 13%, so the INR needs close checks when starting or changing the dose.
  • Rifampicin. This antibiotic cut etoricoxib levels by 65%, which can bring pain back.
  • Methotrexate. In one study 120 mg raised methotrexate levels by 28%.

The usual NSAID effects apply too: more bleeding with blood thinners and SSRIs, higher lithium levels, and weaker blood pressure tablets and diuretics.

Who should be careful

Talk to your doctor before starting or continuing etoricoxib if you have high blood pressure, high cholesterol or diabetes, smoke, or have had a heart attack, stroke, angina, mini-stroke or circulation problems in the legs. The same goes if you have had a stomach ulcer, have kidney or liver disease, take a blood thinner or low-dose aspirin, or are pregnant or breastfeeding. It is not licensed for anyone under 16.

The UK maximums are 60 mg a day for osteoarthritis, 90 mg for rheumatoid arthritis and ankylosing spondylitis, and 120 mg for gout attacks for no more than 8 days. Higher doses have not been shown to work better. Do not take it with other NSAIDs. Large overdoses have rarely caused harm, but call NHS 111 in the UK or your local poison centre. A lower score is no reason to stop a medicine your doctor prescribed.

How we scored it

Dependence (97) and Overdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (85) are strong. Serious side effects (52) sit below diclofenac's because the heart risk matches high-dose diclofenac while blood pressure and heart failure effects are larger. Regulatory warnings (30) are among the lowest for any NSAID: an FDA rejection, strict European heart and blood pressure ContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary, and a full ban in pregnancy.

Questions people ask

Why is etoricoxib not available in the US?

Merck applied for a 60 mg osteoarthritis dose in December 2003. In April 2007 an FDA advisory committee voted 20 to 1 against approval, and on 27 April 2007 the FDA sent a non-approvable letter asking for more data on benefit and risk. The worry was heart attacks and strokes, coming less than three years after Merck withdrew Vioxx, a close relative. Etoricoxib stayed on sale elsewhere.

Is etoricoxib safer than diclofenac?

For the stomach, somewhat. In the MEDAL programme etoricoxib caused about 30% fewer upper stomach and bowel problems than diclofenac 150 mg, though the most serious complications were about equal. Heart attack and stroke rates were the same. Etoricoxib raised blood pressure more, and both drugs now carry the same European heart ContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary.

Does etoricoxib raise blood pressure?

Yes, more than many other NSAIDs, especially at higher doses. The UK label says blood pressure should be controlled before you start, checked within two weeks and then regularly, and that people whose blood pressure stays above 140/90 mmHg must not take it. In the MEDAL trials up to 2.6% of patients stopped etoricoxib because of high blood pressure.

Can I take etoricoxib with the contraceptive pill?

The UK label says the interaction should be considered when choosing a Pill. Etoricoxib raises blood levels of ethinylestradiol by 37% at 60 mg and 50% to 60% at 120 mg, which could raise the risk of side effects such as blood clots in women already at risk. Tell your prescriber which Pill you take.

Can I take etoricoxib with aspirin?

Etoricoxib does not protect the heart the way low-dose aspirin does, so the label says not to stop aspirin you take for that reason. But taking both raises the risk of stomach ulcers and bleeding, and long trials found no clear stomach advantage for coxibs over older NSAIDs when aspirin was added. Ask your doctor whether you need a stomach-protecting medicine.

Is etoricoxib safe in pregnancy?

No. Unlike most NSAIDs, which are limited from about 20 weeks, etoricoxib is ContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary throughout pregnancy and during breastfeeding in its UK label. Talk to your doctor if you are pregnant, planning a pregnancy or breastfeeding.

Sources

  1. 1.Arcoxia 60 mg film-coated tablets, Summary of Product Characteristics (opens in a new tab) · electronic medicines compendium (emc) / Organon, 2025
  2. 2.Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the MEDAL programme: a randomised comparison (opens in a new tab) · The Lancet (Cannon et al.), 2006
  3. 3.Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies (opens in a new tab) · PLOS Medicine (McGettigan and Henry), 2011
  4. 4.Merck receives non-approvable letter from FDA for Arcoxia (etoricoxib) (opens in a new tab) · Merck press release via BioSpace, 2007
  5. 5.No surprise as FDA turns down Merck and Co's Arcoxia (opens in a new tab) · PharmaTimes, 2007
  6. 6.European Medicines Agency concludes action on COX-2 inhibitors (opens in a new tab) · European Medicines Agency, 2005
  7. 7.Etoricoxib: prescribing to patients with high blood pressure (opens in a new tab) · MHRA Drug Safety Update, 2008
  8. 8.Etoricoxib (Arcoxia): revised dose recommendation for rheumatoid arthritis and ankylosing spondylitis (opens in a new tab) · MHRA Drug Safety Update, 2016
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