Piroxicam

Is piroxicam safe?

It works, but it is one of the riskier NSAIDs on the stomach, and it is now rarely prescribed in the US. In a 2012 analysis of observational studies, piroxicam raised the risk of serious stomach bleeding, perforation or blockage 7.43 times compared with no NSAID. Only ketorolac, a drug limited to 5 days, did worse among the common NSAIDs.

Its heart risk looks no worse than other NSAIDs. Europe still restricted it in 2007, because of the stomach and the skin. We score it 65, eight points below its oxicam sister meloxicam (73) and four below diclofenac (69).

What Europe changed in 2007

The European Medicines Agency singled piroxicam out during its 2005 and 2006 reviews of NSAIDs. It found more stomach and bowel side effects and more serious skin reactions than with other non-selective NSAIDs. In June 2007 its committee said the benefits still outweighed the risks, but only within tight limits, and the European Commission made them binding in September 2007:

• no more use for short-term (acute) pain and inflammation
• only for osteoarthritis, rheumatoid arthritis and ankylosing spondylitis
• never as the first NSAID a patient tries
• at most 20 mg a day
• started only by a doctor experienced in long-term inflammatory conditions

The MHRA added that the need for treatment should be reviewed after 14 days and often after that, that people over 80 should avoid it, and that a stomach-protecting medicine should be considered, especially in older people. The US label never adopted those limits. It still lists osteoarthritis and rheumatoid arthritis at 20 mg a day, with the standard NSAID 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.

Stomach and skin

The stomach numbers from the SOS project show how far piroxicam sits from the rest:

In the smaller set of studies that looked only at bleeding, piroxicam came out at 13.4 times, the highest of the eight drugs measured. High daily doses of any NSAID carried two to three times the risk of low ones.

Severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis are very rare with any NSAID. The MHRA says observational studies link piroxicam to more of them than non-oxicam NSAIDs, and most cases start in the first month. Stop the medicine and get medical help at the first sign of a spreading rash, blisters or sores in the mouth.

A 50-hour half-life

Piroxicam lasts far longer than most painkillers. With a half-life of about 50 hours, one dose a day keeps blood levels steady, but it takes 7 to 12 days to reach those levels, and the label says not to judge the effect for two weeks. After the last dose, the drug takes over a week to clear.

That long tail matters for side effects and for overdose, and it is longer still in some people. The liver enzyme CYP2C9CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary clears piroxicam. People with one slow copy of the gene had about 1.7 times normal blood levels in small studies, and one person with two slow copies had 5.3 times. Up to 1% of people carry two slow copies, more in some ethnic groups. The US label suggests a lower dose for known slow metabolisers.

What about the heart?

The data are sparse but not alarming. A 2011 review of population studies found piroxicam's risk of heart attack and stroke was 1.08 times non-use across 8 studies, a result that could be chance and close to naproxen's. Like every prescription NSAID, it still carries the US 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 for heart attack and stroke, and it can raise blood pressure and worsen heart failure.

Who should be careful

Talk to your doctor before starting or continuing piroxicam if you:

• are over 65, and especially over 80
• have had a stomach ulcer, bleed or perforation, or have Crohn's disease or ulcerative colitis
• take a blood thinner, an SSRI, a steroid or low-dose aspirin
• have had a serious skin reaction to any medicine
• have heart disease, high blood pressure, or kidney or liver disease
• take lithium or methotrexate, or are pregnant

Do not take it with other NSAIDs. In an overdose, call Poison Control 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. If you have taken piroxicam for years, ask at your next review whether it is still the right choice.

How we scored it

Dependence (97), track record (90) 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 (80) are strong. Serious side effects (48) are low because the stomach risk is about twice that of most NSAIDs and the skin risk is higher, even though heart risk looks average. Regulatory warnings (28) reflect the US 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 and the EU's 2007 restrictions.