Nitrofurantoin hypersensitivity reactions

Nitrofurantoin administration may result in nausea, vomiting, anorexia, rash, peripheral neuropathy, headache, brown discoloration of the urine, and hypersensitivity reactions, which may range from mild to severe Acute and chronic pulmonary reactions also have been seen. 

Anorexia, nausea, and vomiting are the principal side effects of nitrofurantoin. Neuropathies and hemolytic anemia occur in glucose-6-phosphate dehydrogenase deficiency. Nitrofurantoin antagonizes the action of nalidixic acid. Rashes, pulmonary infiltration and fibrosis, and other hypersensitivity reactions have been reported. 

Immunologic Hypersensitivity reactions to nitrofurantoin have been reported. 

The time frame in which pulmonary drug-induced toxicity occurs is also highly variable, ranging from acute hypersensitivity reactions (e.g., methotrexate, nitrofurantoin toxicides) to delayed presentations (e.g., nitrosoureas, or radiation recall seen with bleomycin, as discussed below). This along with the fact that combination treatments have become commonplace, in particular in the context of chemotherapy protocols, may further hamper the clinician s ability to identify the culprit medication. In addition, several drugs may be implicated in an additive or synergistic fashion and further confuse the clinical picture. 

The incidence of gastrointestinal side-effects including nausea, vomiting and diarrhoea with nitrofurantoin is as high as 30% with standard microcrystalline formulations and patients should be advised to take the doses with food. Other important but less common adverse reactions include pulmonary fibrosis, peripheral neuropathy and hypersensitivity. Patients should also be warned that nitrofurantoin can colour the urine yellow or brown. 

Acute lung reactions to nitrofurantoin are extremely rare in children (12). Lung tissue findings in acute reactions have shown minor vasculitis, granulomatous vasculitis (hypersensitivity angiitis), proliferation of endothelial cells, and empty alveoli (13). Rapidly progressing bronchiolitis obliterans with organizing pneumonia (BOOP) has been reported (14). 

Because these phenomena are also observed in other acute pulmonary reactions caused by antigen-antibody complexes, it is supposed that nitrofurantoin acts similarly, although Goldstein and Janicki (1974) had no success in demonstrating the specific antibody. In contrast, Pearsell et al. (1974) assume that pathogenesis is based on hypersensitivity of the prolonged type (cell-bound immune response). 

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