Nitrofurantoin is not effective for the treatment of parenchymal infections of unilaterally non-functioning kidney. A surgical cause for infection should be excluded in recurrent or severe cases.
Since pre-existing conditions may mask adverse reactions, Nitrofurantoin should be used with caution in patients with renal impairment, pulmonary disease, hepatic dysfunction, neurological disorders, and allergic diathesis.
Neuropathy
Peripheral neuropathy and susceptibility to peripheral neuropathy, which may become severe or irreversible, has occurred and may be life threatening. Therefore, treatment should be stopped at the first signs of neural involvement (paraesthesiae).
Nitrofurantoin should be used with caution in patients with renal impairment, anaemia, diabetes mellitus, electrolyte imbalance, debilitating conditions and vitamin B (particularly folate) deficiency.
Patients with Renal impairment
Nitrofurantion should be used with caution in patients with renal impairment see sections 4.2 and 4.3. Patients with mild to moderate renal dysfunction will require adequate monitoring, as they may experience an increase in pulmonary adverse events when taking Nitrofurantoin see Section 4.2 and 4.8.
Nitrofurantoin is not recommended for use in patients with severe renal impairment see section 4.3
Pulmonary reactions
Acute, subacute and chronic pulmonary reactions have been observed in patients treated with nitrofurantoin. If these reactions occur, nitrofurantoin should be discontinued immediately. Acute pulmonary reactions occur within the first week of treatment and are reversible. If any of the following respiratory reactions occur the drug should be discontinued. Acute pulmonary reactions usually occur within the first week of treatment and are reversible with cessation of therapy. Acute pulmonary reactions are commonly manifested by fever, chills, cough, chest pain, dyspnoea, pulmonary infiltration with consolidation or pleural effusion on chest x-ray, and eosinophilia. In subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form.
Chronic pulmonary reactions occur rarely in patients who have received continuous therapy for six months or longer and are more common in elderly patients.
Chronic pulmonary reactions (including pulmonary fibrosis and diffuse interstitial pneumonitis) can develop insidiously, and may occur commonly in elderly patients. Close monitoring of the pulmonary condition of patients receiving long-term therapy is warranted (especially in the elderly).
Changes in ECG have occurred, associated with pulmonary reactions. Minor symptoms such as fever, chills, cough and dyspnoea may be significant. Collapse and cyanosis have been reported rarely. The severity of chronic pulmonary reactions and their degree of resolution appear to be related to the duration of therapy after the first clinical signs appear. It is important to recognise symptoms as early as possible. Pulmonary function may be impaired permanently, even after cessation of therapy. Lupus-like syndrome associated with pulmonary reactions to nitrofurantoin has been reported (see section 4.8).
Laboratory Tests
Urine may be coloured yellow or brown after taking Nitrofurantoin. Patients on Nitrofurantoin are susceptible to false positive urinary glucose (if tested for reducing substances).
Hematologic Effects
Nitrofurantoin may cause haemolysis in patients with glucose-6-phosphate Dehydrogenase deficiency (Ten percent of black patients and a variable Percentage of ethnic groups of Mediterranean, Near Eastern and Asian origin). Haemolysis ceases when the drug is discontinued. Agranulocytosis, leucopenia, granulocytopenia, haemolytic anaemia, thrombocytopenia, glucose-6-phosphatedehydrogenase deficiency anaemia, megaloblasticanaemia and eosinophilia have occurred. Aplastic anaemia has been reported rarely. Cessation of therapy has generally returned the blood picture to normal.
Clostridium difficile associated diarrhea (CDAD)
Gastrointestinal reactions may be minimised by taking the drug with food or milk or by adjustment of dosage.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including nitrofurantoin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Hepatotoxicity
Hepatic reactions including cholestatic jaundice and chronic active hepatitis occur rarely. Fatalities have been reported. Cholestatic jaundice is generally associated with short-term therapy (usually up to two weeks). Chronic active hepatitis, occasionally leading to hepatic necrosis is generally associated with long-term therapy (usually after six months). The onset may be insidious. Treatment should be stopped at the first sign of hepatotoxicity. Rarely liver failure (which may be fatal) have been reported after nitrofurantoin usage.
For long term treatment, monitor patient closely for appearance of hepatitis (or liver damage), pulmonary or neurological symptoms and other evidence of toxicity. Discontinue treatment with nitrofurantoin if otherwise unexplained pulmonary, hepatotoxic, haematological or neurologic syndromes occur.
Carcinogenicity
There has been limited evidence of carcinogenic effects of nitrofurantoin in experimental animals, but the drug has not been shown to be carcinogenic in humans.
Antimicrobial agents
As with other antimicrobial agents, superinfections by fungi or resistant organisms such as Pseudomonas may occur. However, these are limited to the genitourinary tract because suppression of normal bacterial flora does not occurs elsewhere in the body.
Lactose
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.