Severe cholestatic hepatitis induced by pyritinolBMJ 2004; 328 doi: https://doi.org/10.1136/bmj.328.7439.572 (Published 04 March 2004) Cite this as: BMJ 2004;328:572
- Vasco Maria, assistant professor (firstname.lastname@example.org)1,
- Adriana Albuquerque, research student1,
- Ana Loureiro, research student1,
- Ana Sousa, senior investigator1,
- Rui Victorino, chairman professor1
- Institute of Molecular Medicine, Clinical Immunology Unit and Department of Medicine 2, Faculty of Medicine of Lisbon, Hospital of Santa Maria, Av Prof Egas Moniz, 1649-028 Lisbon, Portugal
- Correspondence to: V Maria
- Accepted 28 November 2003
Pyritinol is a pyrithioxine derivative marketed in more than 50 countries worldwide. It is approved for “symptomatic treatment of chronically impaired brain function in dementia syndromes” and for “supportive treatment of sequelae of craniocerebral trauma” in various European countries, including Austria, Germany, France, Italy, Portugal, and Greece. In France it is also approved for rheumatoid arthritis as a disease modifying drug, on the basis of the results of clinical trials.1 It is not licensed for use in the United Kingdom, but in many countries it is available over the counter and is widely advertised on the internet as being for “memory disturbances.” From the known sales data, we estimate that more than 100 000 individuals in European Union countries have taken pyritinol in the past five years (assuming a daily dose is 600 mg a day and an average treatment lasts 120 days).
Ascribing severe adverse reactions to drugs such as pyritinol—generally considered innocuous by patients and doctors—is particularly difficult as a link with such drugs is not usually considered. We report on six previously healthy subjects who developed a severe and prolonged form of cholestatic hepatitis during pyritinol treatment and in whom unexpectedly high in vitro CD4+ T cell responses to the drug were documented.
Case 1—A 23 year old female student complained of nausea, malaise, and jaundice one month after starting pyritinol 600 mg a day for “memory improvement.” She had also been taking paracetamol with codeine sporadically for some years because of headache. Discontinuation of pyritinol led to rapid clinical improvement and to normalisation of liver function five months later.
Case 2—An 18 year old female student was prescribed nitrofurantoin 400 mg a day for cystitis and pyritinol 600 mg a day for “memory improvement.” Five days later she was admitted to hospital with …