15. Agranulocytosis/Neutropenia
Drug-induced neutropenia can occur in association with various analgesics, psychotropics, anticonvulsants, antithyroid drugs, antihistaminics, antirheumatics, GI drugs, antimicrobials, cardiovascular drugs, and, as expected, with chemotherapy drugs. [74–76]. Immune-mediated mechanisms are associated with some drugs such as penicillins which act as a haptens inducing antibody formation against neutrophils. Clozapine accelerates apoptosis of neutrophils, and propythiouracil causes complement mediated destruction of neutrophils. Drugs such as β-lactam antibiotics, carbamazepine, and valproate have a dose-dependent inhibition of granulopoiesis. Drugs with direct toxic effects on myeloid precursors include ticlopidine, bulsufan, methamizole, ethosuximide, and chlorpromazine.
Treatment of drug-induced neutropenia includes withdrawing the drug, antibiotic coverage when appropriate, and increasingly administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). The use of CSFs can reduce the duration of neutropenia, the frequency of infection, and possibly mortality, particularly in patients with profound neutropenia [76]. Mortality, although lower than in the past, remains about 5%.
Rituximab, an anti-CD20 antibody, used in the treatment of B cell lymphoproliferative disorders and in benign autoimmune disorders, can induce neutropenia, typically of delayed-onset [77].