Hepatotoxicity methyldopa

Methyldopa has been used for approximately 15 years. The most common side effects are somnolence, hemolytic anemia (rare), appearance of a direct Coombs test (frequent), methyldopa fever and hepatotoxicity (rare). 

When AAAD is inhibited, more L-dopa is converted hy COMT to 3-0-methyldopa, a partial agonist at DA receptors that can also compete with L-dopa for uptake into the CNS. These drugs inhibit peripheral COMT, enhancing the CNS uptake of L-dopa and possibly reducing its on-off effects. Tolcapone is hepatotoxic. 

The second adverse effect is not so firmly established as hepatotoxicity. Con-STON (1974) reported a fatal case of myocarditis which he claimed was caused by a hypersensitivity reaction to methyldopa five more fatal cases were reported by Mullick and McAllister (1977). The latter five patients all had associated hepatic lesion. The main piece of evidence cited which the authors claim suggested an immunological mechanism was that histology of the lesions showed a lymphocyte infiltration with a large number of eosinophils. 

Slim R, Ben Salem C, Hmouda H, Bouraoui K. Hepatotoxicity of alpha-methyldopa in pregnancy. J Clin Pharm Ther 2010 35(3) 361-3. 

---