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Patients with abnormal liver function tests are encountered commonly by pharmacists. It is therefore
PRACTICE TOOLS
helpful to know how to amend patients’ treatments and when such amendments might be necessary
Statins Moderate rises of transaminases (ie, less than three times Phenytoin Phenytoin is an enzyme inducer and it is common for
the upper limit of normal [ULN]) have been reported following the three- to five-fold increases in gamma glutaryltransferase to be
use of all statins. This increase may be transient or sustained. The observed during treatment. Hepatotoxicity that requires withdrawal
general advice from manufacturers is to discontinue therapy if the of the drug is less common. If hypoalbuminaemia is observed in
rise is progressive (ie, more than three times the ULN and patients who are taking phenytoin, more of the drug will be
persistent). unbound in plasma. Consequently, a corrected concentration of
phenytoin should be calculated as follows:
Methotrexate Abnormal LFTs and hepatic cirrhosis have been
reported from the use of methotrexate, therefore regular monitoring Measured plasma concentration (μmol/L)
Corrected concentration =
is required. If abnormal LFTs develop, treatment should be (0.9 × serum albumin (g/L) / 44) + 0.1
stopped. In some cases (eg, when patients have been taking a
particularly high dose), it may be possible to restart treatment at a Herbal medicines Increased use of herbal medicines has led to
lower dose once the LFTs return to normal. their greater recognition as a cause of liver injury. Kava and black
cohosh are commonly associated with hepatotoxic reactions. Most
Antituberculous drugs Modest rises in transaminases are not suspected reactions that have been reported to the UK Committee
uncommon in patients with tuberculosis (TB). The British Thoracic on Safety of Medicines regarding radix polygoni multiflori have
Society guidelines for the management of TB3 recommend described hepatobiliary disorders.
CP, Sep, p363-66, how to_FAQ 26/8/09 10:39 Page 366
prescribed at the same time as drugs that larger increases may be considered pancreatic cancer), many medicines can be
PRACTICE TOOLS
are hepatotoxic. Also, inducers of acceptable (see examples, Box 2, p364). continued as normal. If medicines are
cytochrome P450 2E1 (eg, alcohol, stopped and the patient’s LFTs improve,
rifampicin) raise the risk of hepatotoxicity When were the patient’s medicines started? the changes are likely to be drug-induced.
caused by paracetamol and isoniazid. Predictable hepatotoxic reactions usually
have a latency period ranging from hours References
Appropriate action to weeks, whereas idiosyncratic reactions 1 North-Lewis P (editor). Drugs and the Liver. London:
Pharmaceutical Press; 2008.
Since abnormal LFTs do not always can take several months to occur. 2 Walker R, Whittlesea C. Clinical Pharmacy and
indicate hepatic dysfunction and may not Therapeutics. 4th edition. London: Churchill
Livingstone; 2007.
be drug-induced, changes to a patient’s Does the patient have a history of hepatotoxic 3 Joint tuberculosis committee of the British Thoracic
drug therapy are not always needed. drug reactions? There is known cross- Society. Chemotherapy and management of
tuberculosis in the United Kingdom: recommendations
Nonetheless, if abnormal LFTs (with or sensitivity between some groups of 1998. Thorax 1998;53:536–48.
without clinical jaundice) are observed, the medicines (eg, between phenothiazines,
following should be considered: tricyclic antidepressants and NSAIDs).
Are the abnormal values significant? If enzyme Have any other tests been performed that offer NOTE Clinical Pharmacist PRACTICE TOOLS do not
constitute formal practice guidance. Articles in
levels are more than twice the upper limit of alternative explanations for the abnormal
the series have been commissioned from
normal (ULN), this is generally considered LFTs? When there is another explanation independent authors who have summarised useful
to be significant. However, for some drugs for deranged LFTs (eg, gallstones or clinical skills.