Monday, March 14, 2016

Liver Toxicity : Penicillin G and V

Hepatotoxicity
  • Rare instances of idiosyncratic liver injury have been reported in persons receiving the first-generation penicillins.
  • Many case reports pre-dated availability of serologic testing for viral hepatitis and many described patients with multiple reasons for having liver disease (such as sepsis) and who were receiving other potentially hepatotoxic agents.
  • Three distinct forms of liver injury can occur with the first generation penicillins:
(1) transient, asymptomatic elevations in serum aminotransferase levels 
  • with prolonged high doses of parenteral penicillin / IM
  • usually asymptomatic and resolve rapidly with stopping therapy or switching to another antibiotic
  • Jaundice and elevations in alkaline phosphatase are usually absent or mild. 
  • most common with oxacillin and carbenicillin, but can occur with parenteral forms of the first generation penicillins as well
(2) minor liver injury 
  • associated with severe hypersensitivity reactions, and
  • severe hypersensitivity reactions to penicillin, such as Stevens-Johnson syndrome or anaphylaxis, may have an accompanying liver injury and jaundice
  • Generalized allergic reactions to penicillin may be accompanied by granulomas in the liver, spleen and kidney, but are usually without evidence of specific hepatitis injury.  
  • are associated with hypersensitivity reactions, but liver injury is usually overshadowed by the allergic complications (rash, fever, anaphylaxis). 
(3) idiosyncratic, delayed cholestatic hepatitis.
  • isolated case reports
  • Symptoms of nausea, abdominal discomfort, jaundice and pruritus generally arise 1 to 4 weeks after starting therapy and often a few days or weeks after completing a course. 
  • The serum enzyme pattern is usually cholestatic, but may be hepatocellular if tested soon after onset. 
  • Immunoallergic features are common but autoantibody formation is rare
  • Most cases are mild-to-moderate in severity and resolve rapidly
  • quite rare with the natural penicillins, more common with certain broad spectrum penicillins (cloxacillin, flucloxacillin) and is most common with amoxicillin with clavulanic acid
Management
  • asymptomatic rise in serum aminotransferase levels that occurs with high dose penicillin therapy usually resolves rapidly once penicillin is stopped. 
  • These patients may tolerate another form of penicillin without recurrence. 
  • In the few cases of cholestatic hepatitis that have been described with the first generation penicillins, patients have recovered although recovery was slow in some instances (2 to 6 months).
  • Fatal cases of penicillin-associated liver injury have been described but usually in association with severe allergic reactions such as Stevens-Johnson syndrome in which shock and ischemic hepatitis may have contributed to the outcome.  
  • Patients with idiosyncratic liver injury attributed to penicillin should not be re-exposed to other penicillins
References:
  1. http://livertox.nih.gov/PenicillinGandPenicillinV.htm
  2. www.drugs.com

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