Diclofenac

Is diclofenac safe?

Diclofenac gel is a low-risk option for arthritis in a knee or a hand. Diclofenac tablets are an effective painkiller but carry more heart risk than the other common NSAIDs, so they are not a casual choice for anyone with heart disease or its risk factors. The same drug sits behind both: Voltaren in the US, Voltarol in the UK, and dozens of generics, sold as tablets, capsules, suppositories, injections, gels and plasters.

We score diclofenac 69, below ibuprofen (74) and naproxen (73). The gap is mostly the heart. Europe acted on it in 2013 by barring tablets for people with established heart or circulation disease, and the UK took oral diclofenac off open sale in 2015.

Diclofenac and the heart: what changed in 2013

In 2013 the Coxib and traditional NSAID Trialists' Collaboration pooled individual data from randomised trials in The Lancet. High-dose diclofenac (150 mg a day) raised major vascular events by 41% and major coronary events by 70%, almost exactly like the coxibs. In absolute terms, of 1,000 people given diclofenac for a year, about three more had a major vascular event than on placebo, one of them fatal. High-dose naproxen showed no such rise.

That June the European Medicines Agency's safety committee concluded the arterial clot risk of systemic diclofenac was similar to the coxibs, and the EU adopted the coxib rules. In the UK, the MHRA made diclofenac tablets contraindicatedContraindicationA 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 in people with:

• ischaemic heart disease, such as angina or a past heart attack
• peripheral arterial disease
• cerebrovascular disease, including a past stroke or mini-stroke
• heart failure (NYHA class II to IV)

People with high blood pressure, high cholesterol, diabetes or who smoke should only start it after careful thought. In January 2015 the UK went further and made all oral diclofenac prescription-onlyPrescription-only medicineA medicine that can be supplied only with a prescription from a doctor or another authorised prescriber.More in the glossary.

Later data agree. A 2018 Danish study in the BMJ compared people starting different painkillers. Major cardiovascular events within 30 days were 50% more common after starting diclofenac than with no NSAID, 20% more common than after starting ibuprofen or paracetamol, and 30% more common than after naproxen. The risk rose even at low doses.

Gel versus tablets

The difference is large. The UK label for Voltarol Emulgel says about 6% of the applied dose is absorbed, and blood levels peak about 100 times lower than after a tablet. The 2013 heart contraindicationsContraindicationA 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 explicitly do not apply to gels or creams. A 2016 Cochrane review found topical diclofenac relieved knee osteoarthritis pain better than a dummy gel, with about 1 extra person in 10 helped, and roughly matched oral NSAIDs in the few direct comparisons. Its main side effect was mild skin irritation.

The US gel label is for arthritis in those joints only, not for sprains or back pain, and says it may take up to 7 days to work. Do not use a heating pad or a bandage over it. Using the gel with a diclofenac tablet adds the doses together.

Stomach and liver

Diclofenac's stomach risk is real but a little lower than naproxen's or ibuprofen's at high doses: the Lancet analysis put its rise in serious upper gut complications at 1.89 times placebo, against about 4 times for high-dose naproxen and ibuprofen. The Danish study still found a 4.5-fold rise in upper gut bleeding in the first 30 days compared with no NSAID. Black stools, vomiting blood or stomach pain that does not ease need urgent care.

The liver is where diclofenac stands out among NSAIDs. In label trials about 2% of patients had liver enzyme rises above 3 times normal, and in one 3,700-patient study about 1% had marked rises above 8 times normal, more often than on other NSAIDs. Most showed up in the first two months. Severe liver injuryDrug-induced liver injuryLiver damage caused by a medicine, herbal product or supplement. It is usually rare and unpredictable, but it can be serious.More in the glossary, sometimes leading to transplant or death, has been reported, so the label advises liver tests within 4 to 8 weeks of starting long-term use.

Who should be careful

Talk to your doctor or pharmacist before taking diclofenac tablets if you have had a heart attack, stroke, angina or heart failure, have high blood pressure, diabetes or high cholesterol, smoke, are over 60, have had a stomach ulcer, have kidney or liver disease, have asthma that reacts to aspirin, or take a blood thinner, an SSRI, lithium, methotrexate or a diuretic with an ACE inhibitor or ARB. Avoid NSAIDs from 20 weeks of pregnancy unless a doctor advises otherwise.

An overdose of tablets usually causes stomach upset and drowsiness, but large amounts can cause convulsions, kidney failure or liver damage. Call Poison Help on 1-800-222-1222 in the US or NHS 111 in the UK. A lower score is no reason to stop a medicine your doctor prescribed; ask at your next review whether it is still the right painkiller for you.

How we scored it

Dependence (97), track record (95) and overdose marginOverdose 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 (82) are strong. Serious side effects (55) sit below ibuprofen and naproxen because of the coxib-like heart risk and the rarer liver injuryDrug-induced liver injuryLiver damage caused by a medicine, herbal product or supplement. It is usually rare and unpredictable, but it can be serious.More in the glossary. Regulatory warnings (35) reflect the boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary plus the 2013 European heart contraindicationsContraindicationA 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 the 2015 UK prescription-onlyPrescription-only medicineA medicine that can be supplied only with a prescription from a doctor or another authorised prescriber.More in the glossary rule. The score is for systemic use; the gel is a lower-risk way to use the same drug.