Ofloxacin is a second generation fluoroquinolone that was previously used widely for therapy of mild-to-moderate bacterial infections, but which has been replaced by more potent and less toxic fluoroquinolones and is now used largely topically as eye and ear drops. Ofloxacin has been linked to rare instances of acute hepatocellular injury.
Ofloxacin (oh flox' a sin) is an oral, second generation fluoroquinolone that was previously widely used to treat mild-to-moderate urinary and respiratory tract infections caused by susceptible organisms. Ofloxacin is a semisynthetic antibiotic and a racemic mixture; its l-enantiomer is available as levofloxacin which continues to be a widely used antibiotic. Like other fluoroquinolones, ofloxacin is active against a wide range of aerobic gram-positive and gram-negative organisms and is believed to act by inhibition of type II DNA toposiomerases (gyrases) that are required for synthesis of bacterial mRNAs (transcription) and DNA replication. Ofloxacin was approved for use in the United States in 1990, but was discontinued by its initial sponsor in 2009, partially because of the frequency of adverse side effects. Nevertheless, ofloxacin remains available several in generic forms as 200, 300 and 400 mg tablets. Current indications are acute bronchitis, community acquired pneumonia, skin, infections, cystitis, pelvic inflammatory disease, prostatitis, urethritis and gonorrhea. Typical doses are 200 to 400 mg every 12 hours for 3 to 10 days, but longer courses are sometimes used for complicated or recurrent infections. Common side effects include gastrointestinal upset, headaches, skin rash and allergic reactions. Less common but more severe side effects of fluoroquinolones include prolongation of the QT interval, seizures, hallucinations, tendon rupture, hypersensitivity reactions and photosensitivity.
Mild elevations in ALT and alkaline phosphatase levels occur in 1 to 2% of patients on ofloxacin. These abnormalities are generally mild, asymptomatic and transient, resolving even with continuation of therapy. Ofloxacin has also been linked to rare but occasionally severe and even fatal cases of acute liver injury. The time to onset is typically short (2 days to 2 weeks) and the presentation is often abrupt with nausea, fatigue, abdominal pain and jaundice. 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. Cases with a cholestatic pattern of enzymes may run a prolonged course but are usually self-limiting. Many (but not all) cases have had allergic manifestations with fever, rash and eosinophilia. Autoantibodies are usually not present. The hepatotoxicity of ofloxacin is similar to that of other fluoroquinolones and appears to represent a class effect.
Mechanism of Injury
The cause of hepatic injury is unknown, but appears to be hypersensitivity.
Outcome and Management
The severity of ofloxacin induced liver injury ranges from mild and transient serum enzyme elevations to self-limited jaundice to acute liver failure. Recovery is usually rapid (2 to 8 weeks) after stopping the medication. Cross reactivity of the hepatic injury between different fluoroquinolones has not been well defined, 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, particularly levofloxacin which is the levorotatory isomer of ofloxacin.
Drug Class: Antiinfective Agents
Other Drugs in the Subclass, Fluoroquinolones: Ciprofloxacin, Delafloxacin, Gemifloxacin, Levofloxacin, Moxifloxacin, Norfloxacin
Ofloxacin – Generic, Floxin®
|DRUG||CAS REGISTRY NO||MOLECULAR FORMULA||STRUCTURE|