Nitrofurantoin precautions

List of precautions
Information for patients General Drug/lab test interactions Carcinogenesis Mutagenesis Impairment of fertility Pregnancy Labor & delivery Nursing mothers Pediatric use Superinfection Hemolysis Peripheral neuropathy Pseudomembranous colitis Pulmonary reactions Geriatric use
 * Teratogenic effects
 * Non-Teratogenic effects

Information for patients
Patients should be advised to take Nitrofurantoin monohydrate/macrocrystals capsules with food (ideally breakfast and dinner) to further enhance tolerance and improve drug absorption. Patients should be instructed to complete the full course of therapy; however, they should be advised to contact their physician if any unusual symptoms occur during therapy. Patients should be advised not to use antacid preparations containing magnesium trisilicate while taking Nitrofurantoin monohydrate/macrocrystals capsules. Patients should be counseled that antibacterial drugs including Nitrofurantoin monohydrate/macrocrystals capsules should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Nitrofurantoin monohydrate/macrocrystals capsule is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Nitrofurantoin monohydrate/macrocrystals capsules or other antibacterial drugs in the future. Remind patient to shake nitrofurantoin suspension before measuring dose. Instruct patient to take medication with food or milk. Inform patient to expect urine to be orange or brown in color while taking medication. Teach patient importance of completing full course of antibiotic to avoid recurrent infection. Instruct patient to report the following symptoms to health care provider: shortness of breath, difficulty breathing, changes in urination (other than orange discoloration), nausea, vomiting, diarrhea, cramping, skin changes, chest pain, cough, fever, headache, dizziness, vision changes, unusual bleeding (ie, red or black urine or stool), yellowing of skin, light-colored stools or edema. Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction. Return to top

General
Prescribing Nitrofurantoin monohydrate/macrocrystals capsules in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Return to top

Drug/lab test interactions
Urinary creatinine elevation and false-positive urine glucose determination with Benedict reagent (copper sulfate solution) or Fehling's solutions may occur. This has not been observed with the glucose enzymatic test. Return to top

Carcinogenesis
Nitrofurantoin was not carcinogenic when fed to female Holtzman rats for 44.5 weeks or to female Sprague-Dawley rats for 75 weeks. Two chronic rodent bioassays utilizing male and female Sprague-Dawley rats and two chronic bioassays in Swiss mice and in BDF1 mice revealed no evidence of carcinogenicity. Nitrofurantoin presented evidence of carcinogenic activity in female B6C3F1 mice as shown by increased incidences of tubular adenomas, benign mixed tumors, and granulosa cell tumors of the ovary. In male F344/N rats, there were increased incidences of uncommon kidney tubular cell neoplasms, osteosarcomas of the bone, and neoplasms of the subcutaneous tissue. In one study involving subcutaneous administration of 75 mg/kg Nitrofurantoin to pregnant female mice, lung papillary adenomas of unknown significance were observed in the F1 generation. The significance of the carcinogenicity findings relative to the therapeutic use of Nitrofurantoin in humans is unknown. Return to top

Mutagenesis
Nitrofurantoin has been shown to induce point mutations in certain strains of Salmonella typhimurium and forward mutations in L5178Y mouse lymphoma cells. Nitrofurantoin induced increased numbers of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells but not in human cells in culture. Results of the sex-linked recessive lethal assay in Drosophila were negative after administration of Nitrofurantoin by feeding or by injection. Nitrofurantoin did not induce heritable mutation in the rodent models examined. The significance of the mutagenicity findings relative to the therapeutic use of Nitrofurantoin in humans is unknown. Return to top

Impairment of fertility
The administration of high doses of Nitrofurantoin to rats causes temporary spermatogenic arrest; this is reversible on discontinuing the drug. Doses of 10 mg/kg/day or greater in healthy human males may, in certain unpredictable instances, produce a slight to moderate spermatogenic arrest with a decrease in sperm count. Return to top

Pregnancy
Teratogenic Effects Several reproduction studies have been performed in rabbits and rats at doses up to six times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Nitrofurantoin. In a single published study conducted in mice at 68 times the human dose (based on mg/kg administered to the dam), growth retardation and a low incidence of minor and common malformations were observed. However, at 25 times the human dose, fetal malformations were not observed; the relevance of these findings to humans is uncertain. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
 * Pregnancy Category B

Nonteratogenic Effects
 * Nitrofurantoin has been shown in one published transplacental carcinogenicity study to induce lung papillary adenomas in the F1 generation mice at doses 19 times the human dose on a mg/kg basis. The relationship of this finding to potential human carcinogenesis is presently unknown. Because of the uncertainty regarding the human implications of these animal data, this drug should be used during pregnancy only if clearly needed. Return to top

Labor & delivery
Because of the possibility of hemolytic anemia due to immature erythrocyte enzyme systems (glutathione instability), the drug is contraindicated in pregnant patients at term (38 to 42 weeks gestation), during labor and delivery, or when the onset of labor is imminent. Return to top

Nursing mothers
Nitrofurantoin has been detected in human breast milk in trace amounts. Because of the potential for serious adverse reactions from Nitrofurantoin in nursing infants under one month of age, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Return to top

Pediatric use
Nitrofurantoin monohydrate/macrocrystals capsules are contraindicated in infants below the age of one month. Safety and effectiveness in pediatric patients below the age of twelve years have not been established. Return to top

Superinfection
Prolonged or repeated therapy with antibiotics may result in overgrowth of nonsusceptible bacteria or fungi. Return to top

Hemolysis
Hemolytic anemia has occurred, apparently linked to G-6-PD deficiencies. Discontinue at any sign of hemolysis. Return to top

Peripheral neuropathy
May become severe or irreversible; fatalities have been reported. Predisposing conditions such as renal function impairment, anemia, diabetes, electrolyte imbalance, vitamin B deficiency, and debilitating diseases may increase risk. Return to top

Pseudomembranous colitis
Consider in patients who develop diarrhea. Return to top

Pulmonary reactions
Acute and chronic reactions, including interstitial pneumonia, respiratory failure and death, have occurred. Do not give to any patient who has had pulmonary reaction to drug. Return to top

Geriatric use
Clinical studies of Nitrofurantoin monohydrate/macrocrystals capsules did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Spontaneous reports suggest a higher proportion of pulmonary reactions, including fatalities, in elderly patients; these differences appear to be related to the higher proportion of elderly patients receiving long-term Nitrofurantoin therapy. As in younger patients, chronic pulmonary reactions generally are observed in patients receiving therapy for six months or longer. Spontaneous reports also suggest an increased proportion of severe hepatic reactions, including fatalities, in elderly patients. In general, the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients should be considered when prescribing nitrofurantion monohydrate/macrocrystals. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine) are contraindications. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function. Return to top