Reported Adverse Drug Reaction Cases
- ADRAC. Terbinafine and blood dyscrasias. Aust Adv Drug React Bull 2004;23:19.
Life threatening blood dyscrasias with oral terbinafine
Oral terbinafine (Lamisil, Indian Brands Daskil, Fungotek and Lamisil) a Synthetic antifungal is indicated for severe ringworm unresponsive to topical treatment and onychomycosis in adults. Prescribers should be aware that there are three serious, albeit rare, reactions associated with oral terbinafine - white blood cell disorders, severe skin reactions and severe hepatotoxicity. These reactions have not been reported with topical forms of terbinafine (Lamisil cream or gel).
ADRAC reminded health professionals of the association between oral terbinafine and blood dyscrasias in October 2004.1 ADRAC has now received 16 reports of white blood cell dyscrasias with oral terbinafine, including agranulocytosis (7), neutropenia (7) and pancytopenia (2) from a total of 663 reports.
A recent report demonstrates some of the important features of this reaction. A healthy 60 year old female had been taking terbinafine for a month for onychomycosis of the big toe. She developed mouth ulcers, fever and myalgia and presented to hospital with a white blood cell count of 1.3 x 109/L and a neutrophil count of zero. She recovered after treatment with IV antibiotics and granulocyte colony stimulating factor (GCSF).
In this case, the time to onset of around 4 weeks is consistent with 11 other reports to ADRAC, which specified a time to onset of 4-6 weeks. As occurred in the most recent report, the majority of patients develop signs of infection. Recovery is usually rapid following withdrawal of terbinafine and appropriate treatment. Recovery was documented in 11 of the 16 reports, although in one case a 79 year old female developed agranulocytosis about 2 months after initiation of terbinafine, and died from septic shock despite treatment with GCSF and antibiotics. Another characteristic of these reports is the severity of the neutropenia. In the 12 cases where values were reported, they ranged from 0.0-0.9 x 109/L.
Patients taking terbinafine for longer than a month should be advised to be alert for any symptoms of possible infection/neutropenia, such as fever, sore throat or mouth ulcers. Total white blood cell count and neutrophil count should be checked if symptoms develop since a delay in diagnosis is likely to be associated with an increase in morbidity and mortality.
Australian Adverse Drug Reactions Bulletin, Volume 25, Number 4, August 2006