Norfloxacin is a first generation fluoroquinolone that is typically used to treated urinary tract infections and prostatitis. Norfloxacin has been linked to rare instances of acute hepatocellular injury.


Norfloxacin (nor flox' a sin) is a first generation fluoroquinolone that has been available for treatment of bacterial infections for many years, but which now has limited indications and is not commonly used. Like other fluoroquinolones, norfloxacin is active against a wide range of aerobic gram-positive and gram-negative organisms and is believed to act by inhibition of bacterial DNA gyrase and topoisomerase IV that are required for synthesis of bacterial mRNAs (transcription) and DNA replication. In contrast, DNA gyrases are not present in human [and other eukarotic] cells and the equivalent topoisomerases are not sensitive to fluoroquinolone inhibition. Norfloxacin was first approved for use in the United States in 1986. Current indications are for urinary tract infections, sexually transmitted diseases and prostatitis due to sensitive organisms. Based upon studies from Europe, norfloxacin has also been used off-label as prophylaxis against spontaneous bacterial peritonitis in patients with cirrhosis and ascites. Norfloxacin is available as 400 mg tablets under the trade name Noroxin. Typical doses are 400 mg every 12 hours for 3 to 10 days, but chronic therapy has been used for antibacterial prophylaxis. Common side effects include gastrointestinal upset, headaches, skin rash and allergic reactions. Less common, but more severe side effects of norfloxacin include prolongation of the QT interval, seizures, hallucinations, tendon rupture, hypersensitivity reactions, angioedema, Stevens Johnson syndrome, photosensitivity and peripheral neuropathy.


Norfloxacin like other fluoroquinolones is associated with a low rate (1% to 3%) of serum enzyme elevations during therapy. These abnormalities are generally mild, asymptomatic and transient, resolving even with continuation of therapy. Norfloxacin has also been linked to rare but occasionally severe and even fatal cases of acute liver injury. While the numbers of cases have been few, the clinical pattern has been consistent with short latency period of 1 day to 3 weeks and abrupt onset of hepatocellular injury. The pattern of serum enzyme elevations can be either hepatocellular or cholestatic, cases with the shorter times to onset usually being more hepatocellular with markedly elevated ALT levels, and occasionally with rapid worsening of prothrombin time and signs of hepatic failure. The onset of illness may occur a few days after the medication is stopped. Many (but not all) cases have had allergic manifestations with fever, rash and eosinophilia. Autoantibodies are usually not present. Cholestatic and mixed patterns of injury have also been described particularly with delayed recognition of the liver injury. These features are typical of all fluoroquinolone associated hepatotoxicity and the injury is believed to be class specific.

Likelihood score: C (probable rare cause of clinically apparent liver injury).

Mechanism of Injury

The cause of hepatic injury is unknown, but appears to be hypersensitivity.

Outcome and Management

The severity of liver injury caused by norfloxacin ranges from mild and transient serum enzyme elevations to self-limited but severe hepatitis, to acute liver failure and death. Complete recovery is expected after stopping the drug and recovery is usually rapid (2 to 8 weeks). Cross reactivity of the hepatic injury between different fluoroquinolones has not been well documented, but is suspected based upon the similarity of clinical patterns of injury and latency. Thus, patients should be advised to avoid further exposure to the fluoroquinolones.

Drug Class: Antiinfective Agents

Other Drugs in the Subclass, Fluoroquinolones: Ciprofloxacin, Delafloxacin, Gemifloxacin, Levofloxacin, Moxifloxacin, Ofloxacin


Case 1. Cholestatic hepatitis in a patient with cirrhosis due to norfloxacin.(1)

A 58 year old man with alcoholic cirrhosis and acute variceal hemorrhage was treated with intravenous norfloxacin as prophylaxis against spontaneous bacterial peritonitis. After 4 days, he was switched to oral norfloxacin (400 mg twice daily). Five days later, he was noted to be jaundiced and laboratory testing showed increased levels of serum bilirubin (19.1 mg/dL), ALT (214 U/L), and alkaline phosphatase (1921 U/L) as compared to baseline (Table). Tests for hepatitis A, B, C and E were negative as were autoantibodies. Abdominal ultrasound showed no evidence of biliary obstruction. Norfloxacin was stopped and he improved without further intervention over the next several weeks. Six weeks later his blood test results had returned to baseline levels. He was later treated with intravenous ofloxacin without adverse events.

Key Points

Laboratory Values


The abrupt and rapid onset after starting and the rapid resolution on stopping the agent are typical of fluoroquinolone hepatotoxicity. Cases that are cholestatic are less likely to be severe and result in fatalities, but even cholestatic hepatitis has serious implications in patients with cirrhosis. The lack of recurrence with subsequent use of ofloxacin is striking, but it is probably prudent to avoid use of fluoroquinolones in patients with clinically apparent liver injury caused by any agent in that class.



Norfloxacin – Noroxin®


Antiinfective Agents


Product labeling at DailyMed, National Library of Medicine, NIH



Romero-Gómez M, Suárez García E, Fernández MC. Norfloxacin-induced acute cholestatic hepatitis in a patient with alcoholic liver cirrhosis. Am J Gastroenterol. 1999;94:2324–5. [PubMed: 10445586]


References updated: 10 March 2020

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