12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
0621
ACICLOVIR-INDUCED NEUROTOXICITY IN HEMATOLOGICAL PATIENTS. MEASUREMENT
OF THE ACICLOVIR MAIN METABOLITE CMMG MAY DIFFERENTIATE BETWEEN ADVERSE
DRUG REACTIONS AND HERPES INFECTIONS
A. Helldén, O. Odar-Cederlof
Dept of Laboratory Medicine, STOCKHOLM, Sweden
Background. The antiviral drug aciclovir and its prodrug valaciclovir is
commonly used to treat herpes virus infections in hematological
patients. Both drugs have in general low toxicity with GI-disturbances
and headache as common side-effects. However, CNS-symptoms such
as tremor, confusion, hallucinosis and coma have been reported, mainly
in patients with chronic or acute renal failure (ARF). The CNS sideeffects
may confuse the clinical picture and make it difficult to distinguish
between adverse drug reactions (ADRs) and viral infection. It may
result in increased doses of aciclovir instead of withdrawal of the drug.
Other drugs used in hematology patients may also interact on aciclovir
excretion in the kidneys and increase the risk for high aciclovir concentrations,
resulting in acute renal failure, followed by CNS-symptoms. We
have previously shown that the aciclovir main metabolite 9-carboxymethoxymethylguanine
(CMMG) is consistently increased in
serum and CSF in patients with aciclovir-related CNS-symptoms and
that CMMG might have importance as a marker of aciclovir-induced
neurotoxicity. Aims. To increase the knowledge on aciclovir-induced toxicity
in hematological patients. Methods. We present 3 haematological
patients, one with myeloma, one with a mantel cell lymphoma and one
bone marrow transplanted (BMT) patient with chronic myeloid
leukaemia which developed severe aciclovir-related CNS-toxicity
despite doses according to the Swedish Physicians Desk Reference. Aciclovir
and CMMG concentrations were measured in two of the patients.
Results. The BMT patient developed acute renal failure, nightmares and
depression after institution of valaciclovir 500 mg b.i.d. Aciclovir and
CMMG concentrations 16 hrs after last dose were 39 and 29 µmol/L,
respectively (normally