Piroxicam is a commonly used nonsteroidal antiinflammatory drug (NSAID) that is available by prescription only and is used in therapy of chronic arthritis. Piroxicam can cause mild serum aminotransferase elevations and, in rare instances, leads to clinically apparent acute liver injury that can be severe and even fatal.


Piroxicam (pir ox' i kam) belongs to the oxicam family, which is a class of enolic acids structurally unrelated to other NSAIDs. Piroxicam, like other NSAIDs, acts through inhibition of tissue cyclooxygenases (Cox-1 and -2) leading to a decrease in synthesis of pro-inflammatory prostaglandins, which are potent mediators of pain and inflammation. Piroxicam has analgesic as well as antipyretic and antiinflammatory activities. Piroxicam was approved for use in the United States in 1982 and is still widely used, with several million prescriptions filled yearly. Current indications include rheumatoid arthritis and osteoarthritis. Piroxicam is available as capsules of 10 and 20 mg in several generic forms as well as under brand names such as Feldene, Novo-Pirocam and Nu-Pirox. The recommended dose is 10 to 20 mg orally once daily. Piroxicam is available by prescription only. Other oxicam NSAIDs include meloxicam, tenoxicam, and droxicam, the latter two being available in other countries, but not the United States. As with other NSAIDs, piroxicam is generally well tolerated, but side effects can include headache, dizziness, somnolence, dyspepsia, abdominal discomfort, diarrhea, peripheral edema and hypersensitivity reactions. Rare but serious adverse events from NSAIDs include gastrointestinal ulceration and bleeding, increased risk for cardiovascular disease, renal dysfunction and hypersensitivity reactions including anaphylaxis, exfoliative dermatitis and Stevens Johnson syndrome.


Elevated serum aminotransferase levels have been reported in 3% to 18% of patients taking piroxicam, but symptomatic liver disease with jaundice is rare (estimated at 1 to 5 cases per 100,000 prescriptions). The latency to onset of symptoms of clinically apparent liver injury due to piroxicam is variable from a few days to several months, but is generally within the first 1 to 6 weeks of treatment. The pattern of injury is predominantly cholestatic, although cases presenting with mixed or hepatocellular patterns have been reported (Case 1). Eosinophilia, rash and fever can occur, but are not always present and are usually not prominent. Autoantibodies are rarely found. The injury is usually self-limited and recovery occurs within 1 to 2 months. Rare cases of acute liver failure have been reported.

Likelihood score: B (rare but likely cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism of piroxicam induced liver injury is not known, but may be due to a toxic metabolic intermediate of piroxicam metabolism, which occurs largely in the liver. Cases with allergic manifestations (fever, rash, eosinophilia) may also have a component of hypersensitivity.

Outcome and Management

Severity of the liver injury from piroxicam ranges from asymptomatic elevations in serum aminotransferase levels to severe hepatitis with acute liver failure. Several instances of chronic vanishing bile duct syndrome have been attributed to other oxicam NSAIDs, but not specifically to piroxicam. In most instances, however, complete recovery is expected after stopping the drug and usually takes one to two months. Cross sensitivity to liver injury among the various NSAIDs has not been well studied or described. Due to the wide availability of alternative medications, rechallenge with piroxicam and other oxicam forms of NSAIDs (meloxicam, droxicam, tenoxicam) should be avoided.

Drug Class: Nonsteroidal Antiinflammatory Drugs, see also Meloxicam


Case 1. Acute cholestatic hepatitis arising 30 days after starting piroxicam therapy.(1)

A 74 year old woman with chronic arthritis was treated for 30 days with piroxicam and presented 2 days later with pruritus and dark urine followed by jaundice. She had no history of liver disease or exposures to viral hepatitis and did not drink alcohol. She had hypertension and had been treated with atenolol and hydrochlorothiazide chronically. She had no fever or rash, but was jaundiced and had mild hepatic tenderness. Laboratory tests showed a total bilirubin of 6.5 mg/dL and prominent elevations in both ALT and alkaline phosphatase (Table) and eosinophilia. Tests for hepatitis A and B were negative. Ultrasound of the abdomen was normal. A liver biopsy showed intrahepatic cholestasis with minimal portal inflammation suggestive of drug induced liver disease. Her symptoms and jaundice cleared over the next month, and on follow up 3 months later, all liver tests were normal.

Key Points

Laboratory Values


This patient had the onset of itching after a 30 day course of piroxicam. While the “R” value at the onset of injury (3.5) indicated a “mixed” hepatocellular-cholestatic pattern, the course was clearly cholestatic, with prominence of pruritus, further elevations in alkaline phosphatase (and rapid decreases in ALT yielding R values of <2), and a liver biopsy showing intrahepatic cholestasis with only mild inflammation and hepatocellular necrosis. Immunoallergic features were minimal: there was no rash or fever, but "discrete eosinophilia" was said to be present. Other causes of acute liver injury were effectively ruled out, and she recovered steadily once therapy was stopped. Application of the RUCAM causality system to this case gives a score of 8, which suggests that the likelihood that piroxicam is the cause of the injury is highly probable. As in this case, NSAID related hepatotoxicity may be more common in the elderly and among women.



Piroxicam – Generic, Feldene®


Nonsteroidal Antiinflammatory Drugs


Product labeling at DailyMed, National Library of Medicine, NIH



Caballeria E, Masso RM, Arago JV, Sanchis A. Piroxicam hepatotoxicity. Am J Gastroenterol. 1990;85:898–9. [PubMed: 2371992]


References updated: 20 March 2020

Abbreviations: NSAIDs, nonsteroidal antiinflammatory drugs.

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